基本情報

所属

• 獣医学研究院　獣医学部門　環境獣医科学分野

職名

• 准教授

学位

• 博士（獣医学）（北海道大学）

ホームページURL

http://tox.vetmed.hokudai.ac.jp/

科研費研究者番号

• 90647629

J-Global ID

• 201201057197575960

研究キーワード

• 長期慢性暴露   低濃度暴露   腸内細菌叢   LA-ICP-MS   動物種差   歩哨動物   汚染源推定   同位体比   鉛汚染   

研究分野

• 環境・農学 / 環境影響評価
• 環境・農学 / 化学物質影響
• 環境・農学 / 放射線影響
• 環境・農学 / ランドスケープ科学
• 環境・農学 / 環境農学

担当教育組織

•  学士課程　獣医学部
•  博士課程　獣医学院

職歴

• 2022年02月 - 現在 ザンビア大学獣医学部 Visiting Lecturer
• 2021年11月 - 現在 北海道大学大学院獣医学研究院 准教授
• 2012年10月 - 現在 北海道大学大学院獣医学研究院 助教
• 2012年04月 - 2012年10月 日本学術振興会 特別研究員PD
• 2010年04月 - 2012年03月 日本学術振興会 特別研究員DC

所属学協会

• 日本野生動物医学会   Society of Toxicology   Society for Environmental Toxicology and Chemistry   日本環境化学会   日本毒性学会   日本獣医学会   

研究活動情報

論文

• Current situation of lead (Pb) exposure in raptors and waterfowl in Japan and difference in sensitivity to in vitro lead exposure among avian species.

  Mizuki Maruyama, Nana Ushine, Yukiko Watanabe, Chihiro Ishii, Keisuke Saito, Hidefumi Sakai, Takeshi Kuritani, Rio Doya, Kohei Ogasawara, Yoshinori Ikenaka, Yared Beyene Yohannes, Mayumi Ishizuka, Shouta M M Nakayama

  Environmental pollution (Barking, Essex : 1987) 123907 - 123907 2024年04月04日 

  Although lead (Pb) poisoning in wild birds has been considered a serious problem in Japan for over 30 years, there is little information about Pb exposure and its sources throughout Japan except for Hokkaido. Furthermore, to identify and effectively prioritize the conservation needs of highly vulnerable species, differences in sensitivity to Pb exposure among avian species need to be determined. Therefore, we investigated the current situation of Pb exposure in raptors (13 species, N = 82), waterfowl (eight species, N = 44) and crows (one species, N = 6) using concentration and isotope analysis. We employed blood or tissue samples collected in various Japanese facilities mainly in 2022 or 2023. We also carried out a comparative study of blood δ-ALAD sensitivity to in vitro Pb exposure using blood of nine avian species. Pb concentrations in the blood or tissues displayed increased levels (>0.1 μg/g blood) in two raptors (2.4%), ten waterfowl (23%) and one crow (17%). Among them, poisoning levels (>0.6 μg/g blood) were found in one black kite and one common teal. The sources of Pb isotope ratios in ten blood samples with high Pb levels were determined as deriving from shot pellets (N = 9) or rifle bullets (N = 1). In the δ-ALAD study, red-crowned crane showed the highest sensitivity among the nine tested avian species and was followed in order by five Accipitriformes species (including white-tailed and Steller's sea eagle), Blakiston's fish owl, Muscovy duck and chicken, suggesting a genetically driven variance in susceptibility. Further studies on contamination conditions and exposure sources are urgently needed to inform strict regulations on the usage of Pb ammunition. Furthermore, detailed examinations of δ-ALAD sensitivity, interspecific differences, and other factors involved in the variability in sensitivity to Pb are required to identify and prioritize highly sensitive species.
• Effect of chicken manure amendment on lead burden in mice: exposure to lead-spiked soil

  Nyein Chan Soe, Yared Beyene Yohannes, Takamitsu Ohigashi, Hokuto Nakata, Chikae Tatsumi, Yoshitaka Uchida, Walubita Mufalo, Mayumi Ito, Tsutomu Sato, Toshifumi Igarashi, Yoshinori Ikenaka, Mayumi Ishizuka, Shouta M. M. Nakayama

  Journal of Soils and Sediments 2024年03月13日
• Pesticide Contamination Levels in the Stomach Contents of Wild Raccoons (Procyon lotor) and Masked Palm Civets (Paguma larvata) in Japan

  So Shinya, Mariko Sashika, Miku Minamikawa, Tetsuji Itoh, Tsutomu Tanikawa, Kazuyuki D. Tanaka, Shouta M. M. Nakayama, Mayumi Ishizuka, Yoshinori Ikenaka

  Environmental Toxicology and Chemistry 2024年03月05日 

  Abstract Pesticides, which are vital for agriculture, pose a significant threat to wildlife in transformed Japanese landscapes. Despite global reports of pesticide poisoning in animals, limited studies have examined current wildlife exposure in croplands or metropolitan areas in the region. Using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and gas chromatography–tandem mass spectrometry (GC–MS/MS), our study aimed to assess the contamination status of 368 commonly used pesticides. The stomach contents of raccoons living in croplands contained 13 pesticides, including six herbicides and 11 fungicides. Neonicotinoid insecticides, some fungicides, and previously banned insecticides (benzene hexachloride and dichlofenthion) were most frequently detected and found at the highest concentrations, suggesting direct soil–plant transfer and direct consumption by crop‐eating species. In masked palm civets living in metropolitan areas, four insecticides and six fungicides were detected, indicating urban wildlife exposure from raided dustbins, urban gardens, and lumber from houses. Although the maximum measured concentrations of all pesticides were lower than the acceptable daily intake for humans, it remains unclear whether these concentrations may have toxic or adverse health effects on the species evaluated in these transformed landscapes. Our study is the first to examine recent pesticide exposures in wild mammals in Japan. Application of the method we developed will lay the foundation for the examination of pesticides in other wildlife species to assist conservation management efforts in the region. Environ Toxicol Chem 2024;00:1–9. © 2024 SETAC
• Quantification of the tissue distribution and accumulation of the neonicotinoid pesticide clothianidin and its metabolites in maternal and fetal mice.

  Tetsushi Hirano, Shuji Ohno, Yoshinori Ikenaka, Kanoko Onaru, Shizuka Kubo, Yuka Miyata, Mizuki Maeda, Youhei Mantani, Toshifumi Yokoyama, Collins Nimako, Yared Beyene Yohannes, Shouta M M Nakayama, Mayumi Ishizuka, Nobuhiko Hoshi

  Toxicology and applied pharmacology 116847 - 116847 2024年02月07日 

  Neonicotinoids (NNs) are commonly used pesticides that have a selective agonistic action on insect nicotinic acetylcholine receptors. Recent evidence has shown that NNs have adverse effects in the next generation of mammals, but it remains unclear how NNs transferred from dams to fetuses are distributed and accumulated in fetal tissues. Here, we aimed to clarify the tissue distribution and accumulation properties of the NN clothianidin (CLO) and its 6 metabolites in 7 tissues and blood in both dams and fetuses of mice administered CLO for a single day or for 9 consecutive days. The results showed that the total concentrations of CLO-related compounds in the brain and kidney were higher in fetuses than in dams, whereas in the liver, heart, and blood they were lower in fetuses. The multi-day administration increased the total levels in heart and blood only in the fetuses of the single administration group. In addition, dimethyl metabolites of CLO showed fetus/dam ratios >1 in some tissues, suggesting that fetuses have higher accumulation property and are thus at higher risks of exposure to CLO-related compounds than dams. These findings revealed differences in the tissue-specific distribution patterns of CLO and its metabolites between dams and fetuses, providing new insights into the assessment of the developmental toxicity of NNs.
• Insights on hazardous metal bioaccessibility, and groundwater impacted by Zn residues from a legacy mine and risk evaluation of adjacent soils

  Walubita Mufalo, Takahiko Arima, Toshifumi Igarashi, Mayumi Ito, Tsutomu Sato, Shingo Tomiyama, Imasiku Nyambe, Carlito Baltazar Tabelin, Hokuto Nakata, Shouta Nakayama, Mayumi Ishizuka

  Environmental Geochemistry and Health 46 2 2024年02月06日
• Evaluation of anticoagulant rodenticide sensitivity by examining in vivo and in vitro responses in avian species, focusing on raptors

  Kraisiri Khidkhan, Fuyu Yasuhira, Aksorn Saengtienchai, Chaiyan Kasorndorkbua, Ratiwan Sitdhibutr, Kohei Ogasawara, Hikaru Adachi, Yukiko Watanabe, Keisuke Saito, Hidefumi Sakai, Kazuo Horikoshi, Hajime Suzuki, Yusuke K. Kawai, Kazuki Takeda, Yared B. Yohannes, Yoshinori Ikenaka, Barnett A. Rattner, Mayumi Ishizuka, Shouta M.M. Nakayama

  Environmental Pollution 122837 - 122837 2023年11月
• Surveys of eleven species of wild and zoo birds and feeding experiments in white-tailed eagles reveal differences in the composition of the avian gut microbiome based on dietary habits between and within species.

  Kohei Ogasawara, Naoki Yamada, Shouta Mm Nakayama, Yukiko Watanabe, Keisuke Saito, Akane Chiba, Yoshitaka Uchida, Kaoru Ueda, Yasunori Takenaka, Kentaro Kazama, Mami Kazama, Junya Yamagishi, Hazuki Mizukawa, Yoshinori Ikenaka, Mayumi Ishizuka

  The Journal of veterinary medical science 2023年10月31日 

  The composition of the gut microbiome varies due to dietary habits. We investigated influences of diet on the composition of the gut microbiome using the feces of 11 avian species, which consumed grain-, fish- and meat-based diets. We analyzed gut microbiome diversity and composition by next-generation sequencing (NGS) of 16S ribosomal RNA. The grain-diet group had higher gut microbiome diversity than the meat- and fish-diet group. The ratio of Bacteroidetes and Firmicutes phyla was higher in the grain-diet group than in the meat- and fish-diet groups. The grain-diet group had a higher ratio of Veillonellaceae than the meat-diet group and a higher ratio of Eubacteriaceae than the fish-diet habit group. To clarify the influence of diet within the same species, white-tailed eagles (Haliaeetus albicilla, n=6) were divided into two groups, and given only deer meat or fish for approximately one month. The composition of the gut microbiome of individuals in both groups were analyzed by NGS. There were indications of fluctuation in the levels of some bacteria (Lactobacillus, Coriobacteriales, etc.) in each diet group. Moreover, one individual for each group which switched each diet in last week changed to each feature of composition of bacterial flora. The above results show that the composition of the gut microbiome differ depending on diet, even within the same species.
• A stable isotope analysis of the dietary patterns of the aquatic apex predator, the African tigerfish (Hydrocynus vittatus).

  Ruan Gerber, Lizaan de Necker, Johan H J van Vuren, Yoshinori Ikenaka, Shouta M M Nakayama, Mayumi Ishizuka, Victor Wepener, Nico J Smit

  Journal of fish biology 2023年07月27日 

  Stable isotope analyses, specifically δ13 C and δ15 N, are useful tools increasingly used to understand ecosystem function, food web structures and consumer diets. Although the iconic tigerfish, Hydrocynus vittatus, is regarded as an apex predator in southern African freshwater systems, little information is available regarding their feeding behaviour and how this may change with growth or differ between ecosystems with most information stemming from stomach content analyses (SCA). The aim of the present study was to address this lack of information through a baseline study of the diet of large and small tigerfish in various lentic and lotic ecosystems in South Africa using stable isotope methods. Fish and various food web components and food sources were collected from two river and two lake ecosystems from the Lower Phongolo River floodplain, SA. The δ13 C and δ15 N values for all samples were determined and multivariate analyses and Bayesian analytical techniques applied to determine the feeding ecology of H. vittatus and how this may differ with size and habitat type. Analyses revealed a substantial difference in the type and abundance of food sources contributing to the diet of H. vittatus between ecosystems, most prominently between the lotic systems, where less dietary specialisation was observed, and lentic systems where more specialisation was observed. Furthermore, there was a distinct difference in diet between small and large tigerfish, especially in the lotic system, indicating an ontogenetic diet shift as tigerfish grow and further supporting previous SCA studies. This is the first study of its kind on the African continent for H. vittatus and the findings illustrate the value of stable isotope analysis in providing in-depth information into the feeding ecology of consumers and how this may differ between size classes and habitat types. This article is protected by copyright. All rights reserved.
• Evaluation of the Effect of Pb Pollution on Avian Influenza Virus-Specific Antibody Production in Black-Headed Gulls (Chroicocephalus ridibundus)

  Nana Ushine, Makoto Ozawa, Shouta M. M. Nakayama, Mayumi Ishizuka, Takuya Kato, Shin-ichi Hayama

  Animals 13 14 2338 - 2338 2023年07月18日 

  Lead (Pb), an environmental pollutant, has been widely reported to have contaminated mammals, including humans and birds. This study focuses on the effects of Pb pollution on avian influenza virus (AIV) antibody production. A total of 170 black-headed gulls (Chroicocephalus ridibundus) were captured in Tokyo Bay (TBP) from January 2019 to April 2020 and in Mikawa Bay (MBP) from November 2019 to April 2021. The gulls were weighed, subjected to blood sampling, and released with a ring band on their tarsus. The samples were used to measure blood Pb levels (BLL) and AIV-specific antibodies. The BLL were compared using the Wilcoxon two-sample test between the period when black-headed gulls arrived and the wintering period, defined by the number of gulls counted in each area. A significant increase was found in the TBP. A decrease in BLL significantly increased antibody titer during wintering in TBP and MBP. Pb pollution had a negative effect on the production of AIV antibodies. These findings suggest that wild birds that were contaminated by Pb in the environment may facilitate the spread of zoonotic diseases, further increasing the possibility that environmental pollutants may threaten human health.
• A Comparative Genomic and Phylogenetic Investigation of the Xenobiotic Metabolism Enzymes of Cytochrome P450 in Elephants Shows Loss in CYP2E and CYP4A.

  Kanami Watanabe, Mitsuki Kondo, Yoshinori Ikenaka, Shouta M M Nakayama, Mayumi Ishizuka

  Animals : an open access journal from MDPI 13 12 2023年06月09日 

  Cytochrome P450 is an important enzyme that metabolizes a variety of chemicals, including exogenous substances, such as drugs and environmental chemicals, and endogenous substances, such as steroids, fatty acids, and cholesterol. Some CYPs show interspecific differences in terms of genetic variation. As little is known about the mechanisms of elephant metabolism, we carried out a comparative genomic and phylogenetic analysis of CYP in elephants. Our results suggest that elephant CYP genes have undergone independent duplication, particularly in the CYP2A, CYP2C, and CYP3A genes, a unique cluster specific to elephant species. However, while CYP2E and CYP4A were conserved in other Afrotheria taxa, their decay in elephants resulted in genetic dysfunction (pseudogene). These findings outline several remarkable characteristics of elephant CYP1-4 genes and provide new insights into elephant xenobiotic metabolism. Further functional investigations are necessary to characterize elephant CYP, including expression patterns and interactions with drugs and sensitivities to other chemicals.
• Estimation of the relationship between Pb contamination and feeding history of black-headed gulls (Chroicocephalus ridibundus) using stable isotopes

  Nana Ushine, Shouta MM Nakayama, Mayumi Ishizuka, Takuya Kato, Shin-ichi Hayama

  Japanese Journal of Environmental Toxicology 26 25 - 37 2023年06月 [査読有り]
  
• Immobilization of Pb and Zn leached from mining residue materials in Kabwe, Zambia: Performance of calcined dolomite in column experiments

  Walubita Mufalo, Pawit Tangviroon, Takahiko Arima, Toshifumi Igarashi, Mayumi Ito, Tsutomu Sato, Kenta Noto, Takeshi Kawashima, Imasiku Nyambe, Hokuto Nakata, Shouta Nakayama, Mayumi Ishizuka

  Journal of Geochemical Exploration 249 107209 - 107209 2023年06月
• Association between Chronic Environmental Lead (Pb) Exposure and Cytokines in Males and Females of Reproductive Age from Kabwe, Zambia.

  Andrew Kataba, Yared Beyene Yohannes, Hokuto Nakata, John Yabe, Haruya Toyomaki, Kaampwe Muzandu, Golden Zyambo, Yoshinori Ikenaka, Kennedy Choongo, Mayumi Ishizuka, Shouta M M Nakayama

  International journal of environmental research and public health 20 8 2023年04月20日 

  Lead (Pb) poisoning remains a great public health challenge globally known to induce a wide range of ailments in both children and adults. The current study investigated the association of chronic environmental Pb exposure and immunomodulatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8) in adult males and females living in Kabwe, Zambia. The standard human cytokine/chemokine Milliplex assay was used to quantify plasma cytokines from four groups categorized as low (<10 μg/dL) and high (>10 μg/dL) blood lead level (BLL) groups, namely, low BLL female (n = 47; BLL = 3.76 μg/dL), low BLL Male (n = 43; BLL = 4.13 μg/dL), high BLL female (n = 21; BLL = 23.5 μg/dL), and high BLL male (n = 18; BLL = 23.7 μg/dL), respectively. The low BLL group was associated with increased TNF-α levels, and the high BLL group was associated with reduced TNF-α levels in female subjects. No associations between BLL and the levels of IL-8 and TNF-α cytokines were observed in either females or males, respectively. A negative correlation between BLL and TNF-α was found in female subjects, suggesting that an increase in BLL accompanied by a reduction in TNF-α. The reduced levels of circulating TNF-α in female subjects suggest that chronic Pb exposure could predispose females to immune and inflammation-related disorders than their male counterparts. Further studies are recommended to ascertain the impact of chronic Pb exposure on immunomodulatory cytokines, especially in females.
• X-ray analytic microscopy with CT-guided sample extraction to analyze potential projectile fragments in a dead serow.

  Yuko Kihara, Yohsuke Makino, Masaaki Yokoyama, Fumiko Chiba, Aki Tanaka, Shouta M M Nakayama, Shin-Ichi Hayama, Mayumi Ishizuka, Kurt B Nolte, Hirotaro Iwase

  Legal medicine (Tokyo, Japan) 63 102257 - 102257 2023年04月11日 [査読有り]
   

  In forensic pathology, it is important to detect and recover as evidence residual metal particles and projectiles when evaluating potential gunshot wounds. This process can be challenging when the bullets are fragmented. This report presents our experience using multiple modalities to analyze the wound of an illegally killed Japanese serow (Capricornis crispus) found in a mountainous region without its head and hind limbs. We performed postmortem computed tomography (PMCT) and necropsy that showed a distant-range gunshot wound of the neck likely created by a centerfire rifle. A postmortem cut through the neck and absent head precluded a complete evaluation. To determine the composition of the metal-like fragments in the neck, sampling and metal analysis were performed in two ways. Samples extracted from the exposed wound surface without CT guidance were analyzed directly using inductively coupled plasma mass spectrometry (ICP-MS). Samples from the bone, muscles, and cervical cord extracted under CT guidance were analyzed using x-ray analytic microscopy (XGT-9000, HORIBA, Kyoto, Japan). In wound surface samples, silicon and iron were detected as the main components on ICP-MS, suggesting that the materials were gravel. The samples taken under CT guidance and analyzed with XGT-9000 revealed that the high-density CT areas were mainly composed of lead. Combining CT-guided sample extraction and XGT-9000 can be useful for retrieving true projectile fragments and avoiding the confusion created by erroneously sampling non-projectile surface materials.
• Effects of Diazinon Exposure on Urinary Shedding of Leptospira interrogans Serogroup Hebdomadis in Mice

  So Shinya, Devinda S. Muthusinghe, Nobuo Koizumi, Kumiko Yoshimatsu, Shouta M. M. Nakayama, Mayumi Ishizuka, Yoshinori Ikenaka

  Toxics 11 4 2023年04月11日 

  Wild rodents are natural hosts of Leptospira spp. and are exposed to various pesticides, some of which are immunotoxic. Rodent urine is an important source of infection for humans and other animals. We evaluated the effects of pesticide exposure on Leptospira growth in mice. Diazinon, at doses of 0.2, 1, and 5 mg/kg/day, was orally administered continuously to mice infected with Leptospira interrogans serogroup Hebdomadis for 32 days. The numbers of L. interrogans in urine and kidney tissues were significantly lower in mice exposed to 5 mg/kg/day diazinon than in unexposed mice (p < 0.05). The urinary concentration of 2-isopropyl-6-methyl-4-pyrimidinol, the metabolite of diazinon, was comparable with the concentration at which viability of L. interrogans was decreased in in vitro assay, suggesting that it had toxic effects on L. interrogans in the proximal renal tubules. Diazinon exposure reinforced Leptospira-induced expression of inflammatory cytokine genes in kidney tissues, and an enhanced immune system might suppress Leptospira growth. These results suggest that diazinon exposure may not increase the risk of Leptospira transmission to humans through mice. This novel study evaluated the relationship between pesticide exposure and Leptospira infection in mice, and the results could be useful for risk assessment of leptospirosis.
• Characteristics of cytochrome P450-dependent metabolism against acetamiprid in the musk shrew (Suncus murinus).

  So Shinya, Yusuke Kawai, Mitsuki Kondo, Shouta M M Nakayama, Mayumi Ishizuka, Yoshinori Ikenaka

  Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 265 109537 - 109537 2023年03月 

  Soricidae spp. (shrews) play an essential role in soil ecosystems and, due to their habitat and behavior, are exposed to soil pollutants, such as pesticides. Still, toxicity risk in Soricidae spp. has not been appropriately assessed. In this study, the musk shrew (Suncus murinus) was used as a model organism for toxicity assessment in Soricidae. Considering their carnivorous diet, it is reasonable to assume that the musk shrew has unique metabolic traits that are different from those of other common experimental models. This study describes the cytochrome P450 (CYP)-dependent metabolism affected by acetamiprid (ACP), a neonicotinoid insecticide. Pharmacokinetics analysis, an in vitro metabolic assay, and genetic analysis of CYP were performed and compared with data from mice and rats. Through phylogenetic and syntenic analyses, three families of CYP were identified in the musk shrew. Pharmacokinetic analysis showed that the blood concentration of ACP decreased more quickly in musk shrews than in mice. Moreover, the in vitro metabolic assay suggested more efficient metabolic responses toward ACP in musk shrews than in mice or rats. One of the CYP2A isoforms in musk shrews might be linked to a better ACP metabolism. From the results above, we describe novel metabolic traits of the musk shrew. Future research on recombinant CYP enzymes is necessary to fully understand CYP-dependent metabolism of xenobiotics in musk shrews.
• Social cost of mining-related lead (Pb) pollution in Kabwe, Zambia, and potential remediation measures

  Daichi Yamada, Masato Hiwatari, Daiju Narita, Peter Hangoma, Bona Chitah, Hokuto Nakata, Shouta M.M. Nakayama, John Yabe, Mayumi Ito, Toshifumi Igarashi, Mayumi Ishizuka, Golden Zyambo

  Science of The Total Environment 865 161281 - 161281 2023年03月
• Investigation of dichlorodiphenyltrichloroethane (DDT) on xenobiotic enzyme disruption and metabolomic bile acid biosynthesis in DDT-sprayed areas using wild rats.

  Kodai Motohira, Yared Beyene Yohannes, Yoshinori Ikenaka, Akifumi Eguchi, Shouta Mm Nakayama, Victor Wepener, Nico J Smit, Johan Hj VAN Vuren, Mayumi Ishizuka

  The Journal of veterinary medical science 85 2 236 - 243 2023年01月02日 

  Dichlorodiphenyltrichloroethane (DDT) is an organochlorine insecticide used worldwide. Several studies have reported the toxic effects of DDT and its metabolites on steroid hormone biosynthesis; however, its environmental effects are not well understood. This study examined wild rats collected in DDT-sprayed areas of South Africa and quantified plasma metabolites using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). Fold change analysis of the metabolome revealed the effect of DDT on bile acid biosynthesis. Gene expression of the related enzyme in rat liver samples was also quantified. Significant association was found between DDT and gene expression levels related to constitutive androstane receptor mediated enzymes, such as Cyp2b1 in rat livers. However, our results could not fully demonstrate that enzymes related to bile acid biosynthesis were strongly affected by DDT. The correlation between DDT concentration and gene expression involved in steroid hormone synthesis in testis was also evaluated; however, no significant correlation was found. The disturbance of metabolic enzymes occurred in rat liver in the target area. Our results suggest that DDT exposure affects gene expression in wild rats living in DDT-sprayed areas. Therefore, there is a need for DDT toxicity evaluation in mammals living in DDT-sprayed areas. We could not find an effective biomarker that could reflect the mechanism of DDT exposure; however, this approach can provide new insights for future research to evaluate DDT effects in sprayed areas.
• Sensitivity Assessment of Diphacinone by Pharmacokinetic Analysis in Invasive Black Rats in the Bonin (Ogasawara) Archipelago, Japan

  Kazuki Takeda, Keita Shimizu, Miyu Sato, Masafumi Katayama, Shouta MM Nakayama, Kotaro Tanaka, Yoshinori Ikenaka, Takuma Hashimoto, Ryuichi Minato, Yusuke Oyamada, Kazuyuki D. Tanaka, Goro Kimura, Tsutomu Tanikawa, Keisuke Kato, Taichi Kusakabe, Mayumi Ishizuka, Ryo Kamata

  2023年
• Biological effects related to exposure to polychlorinated biphenyl (PCB) and decabromodiphenyl ether (BDE-209) on cats.

  Kraisiri Khidkhan, Hazuki Mizukawa, Yoshinori Ikenaka, Shouta M M Nakayama, Kei Nomiyama, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Shinsuke Tanabe, Mayumi Ishizuka

  PloS one 18 1 e0277689  2023年 

  As an animal familiar to humans, cats are considered to be sensitive to chemicals; cats may be exposed to polychlorinated biphenyls (PCBs) and decabromodiphenyl ether (BDE-209) from indoor dust, household products, and common pet food, leading to adverse endocrine effects, such as thyroid hormone dysfunction. To elucidate the general biological effects resulting from exposure of cats to PCBs and PBDEs, cats were treated with a single i.p. dose of a principal mixture of 12 PCBs and observed for a short-term period. Results revealed that the testis weight, serum albumin, and total protein of the treated group decrease statistically in comparison with those in the control group. The negative correlations suggested that the decrease in the total protein and albumin levels may be disturbed by 4'OH-CB18, 3'OH-CB28 and 3OH-CB101. Meanwhile, the serum albumin level and relative brain weight decreased significantly for cats subjected to 1-year continuous oral administration of BDE-209 in comparison to those of control cats. In addition, the subcutaneous fat as well as serum high-density lipoprotein (HDL) and triglycerides (TG) levels increased in cats treated with BDE-209 and down-regulation of stearoyl-CoA desaturase mRNA expression in the liver occurred. These results suggested that chronic BDE-209 treatment may restrain lipolysis in the liver, which is associated with lipogenesis in the subcutaneous fat. Evidence of liver and kidney cell damage was not observed as there was no significant difference in the liver enzymes, blood urea nitrogen and creatinine levels between the two groups of both experiments. To the best of our knowledge, this is the first study that provides information on the biochemical effects of organohalogen compounds in cats. Further investigations on risk assessment and other potential health effects of PCBs and PBDEs on the reproductive system, brain, and lipid metabolism in cats are required.
• Sulfotransferases (SULTs), enzymatic and genetic variation in Carnivora: Limited sulfation capacity in pinnipeds.

  Mitsuki Kondo, Yoshinori Ikenaka, Shouta M M Nakayama, Yusuke K Kawai, Hazuki Mizukawa, Yoko Mitani, Kei Nomyama, Shinsuke Tanabe, Mayumi Ishizuka

  Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 263 109476 - 109476 2023年01月 

  Wild carnivorans are one of the most important species due to their high positions in the food chain. They are also highly affected by numerous environmental contaminants through bioaccumulation and biomagnification. Xenobiotic metabolism is a significant chemical defense system from xenobiotics because it degrades the activity of a wide range of chemicals, generally into less active forms, resulting in their deactivation. Sulfotransferases (SULTs) are one of the most important xenobiotic metabolic enzymes, which catalyze the sulfonation of a variety of endogenous and exogenous chemicals, such as hormones, neurotransmitters, and a wide range of xenobiotic compounds. Although SULTs are of such high importance, little research has focused on these enzymes in wild carnivorans. In this study, we clarified the genetic properties of SULTs in a wide range of mammals, focusing on carnivorans, using in silico genetic analyses. We found genetic deficiencies of SULT1E1 and SULT1D1 isoforms in all pinnipeds analyzed and nonsense mutations in SULT1Cs in several carnivorans including pinnipeds. We further investigated the enzymatic activity of SULT1E1 in vitro using liver cytosols from pinnipeds. Using a SULT1E1 probe substrate, we found highly limited estradiol sulfonation in pinnipeds, whereas other mammals had relatively high sulfation. These results suggest that pinnipeds have severely or completely absent SULT1E1 activity, which importantly catalyzes the metabolism of estrogens, drugs, and environmental toxins. This further implies a high susceptibility to a wide range of xenobiotics in these carnivorans, which are constantly exposed to environmental chemicals throughout their lifetime.
• Contamination Status of Pet Cats in Thailand with Organohalogen Compounds (OHCs) and Their Hydroxylated and Methoxylated Derivatives and Estimation of Sources of Exposure to These Contaminants

  Makoto Shimasaki, Hazuki Mizukawa, Kohki Takaguchi, Aksorn Saengtienchai, Araya Ngamchirttakul, Disdanai Pencharee, Kraisiri Khidkhan, Yoshinori Ikenaka, Shouta M. M. Nakayama, Mayumi Ishizuka, Kei Nomiyama

  Animals 12 24 3520 - 3520 2022年12月13日 [査読有り][招待有り]
   

  In this study, we analyzed serum samples of pet cats from Thailand and estimated the contribution to organohalogen compounds (OHCs) exposure through cat food and house dust intake. BDE-209 was predominant in cat sera and accounted for 76% of all polybrominated diphenyl ethers (PBDEs). Decabromodiphenyl ether (BDE-209) is a major contaminant in dry cat food and house dust, which has been estimated to be a source of exposure for Thai pet cats. BDE-209 is a major contaminant of OHCs in dry cat food and house dust, which was estimated to be a source of exposure for Thai pet cats. On the other hand, the level of contamination by PCBs was lower than in other countries. Analysis of pet foods suggested that BDE-209 in pet cat serum was attributable to the consumption of dry cat food. On the other hand, house dust also contained high concentrations of BDE-209. Thus, high levels of BDE-209 in pet cat sera can be attributed to the consumption of dry cat food and house dust. These results suggest that pet cats are routinely exposed to non-negligible levels of OHCs.
• Accumulation of Metals in the Environment and Grazing Livestock near A Mongolian Mining Area.

  Bayartogtokh Bataa, Kodai Motohira, Delgermurun Dugar, Tsend-Ayush Sainnokhoi, Lkhamjav Gendenpil, Tserenchimed Sainnokhoi, Bolormaa Pelden, Yared Beyene Yohannes, Sumiya Ganzorig, Shouta M M Nakayama, Mayumi Ishizuka, Yoshinori Ikenaka

  Toxics 10 12 2022年12月10日 

  The Mongolian economy is supported by rich deposits of natural resources, such as copper, coal, and gold. However, the risk of heavy metal pollution to livestock and human have been recently discussed. This research collected various samples from soil and animal (sheep, goat, horse, cow, and camel), blood and organs (kidney and liver) in the Mongolian countryside. These samples were processed, and the concentration of metals was quantified using inductively coupled plasma-mass spectrometry (ICP/MS). As previously reported, arsenic was found at high levels of accumulation in soil. Selenium is another concern, as median concentration in one area exceeded the maximum allowable level. Cadmium and selenium were found to be highly accumulated in animal kidney. This research revealed the current pollution level in Mongolia based on evaluation of soil and animals. The concentration in animals could not indicate that animals had severe effects because of heavy metal exposure. However, kidney is eaten in Mongolia, and so there is a direct connection to human health, and this research suggested the possible risks posed by each edible animal. In particular, evaluation of metals in livestock is rare in Mongolia. This result can contribute to animal and human health in Mongolian communities.
• Detection of Changes in Monoamine Neurotransmitters by the Neonicotinoid Pesticide Imidacloprid Using Mass Spectrometry.

  Anri Hirai, Ryo Yamazaki, Atsushi Kobayashi, Takashi Kimura, Kei Nomiyama, Shuichi Shimma, Shouta M M Nakayama, Mayumi Ishizuka, Yoshinori Ikenaka

  Toxics 10 11 2022年11月17日 

  Monoamine neurotransmitters (MAs), including dopamine (DA) and serotonin (5-HT), regulate brain functions such as behavior, memory, and learning. Neonicotinoids are pesticides that are being used more frequently. Neonicotinoid exposure has been observed to produce neurological symptoms, such as altered spontaneous movements and anxiety-like behaviors, which are suspected to be caused by altered MA levels. However, current neurotoxicity tests are not sufficiently sensitive enough to make these determinations. In this study, we performed some behavior tests, and derivatization reagents to improve the ionization efficiency, which was applied to liquid chromatography mass spectrometry (LC-MS/MS) to reveal the effect of neonicotinoid administration on MAs in the brain. We orally administered the neonicotinoid imidacloprid (0, 10, and 50 mg/kg body weight) to C57BL/6NCrSlc mice. In the behavior tests, a decrease in activity was observed. The LC-MS/MS quantification of MAs in various brain regions showed a decrease in some MA levels in the olfactory bulb and the striatum. These results showed, for the first time, that even a low dose of imidacloprid could alter MA levels in various parts of the brain.
• Characteristics of cytochrome P450-dependent metabolism in the liver of the wild raccoon, Procyon lotor.

  So Shinya, Yared Beyene Yohannes, Yoshinori Ikenaka, Shouta Mm Nakayama, Mayumi Ishizuka, Shoichi Fujita

  The Journal of veterinary medical science 84 12 1665 - 1672 2022年11月02日 

  Wildlife is exposed to a wide range of xenobiotics in the natural environment. In order to appropriately assess xenobiotic-induced toxicity in wildlife, it is necessary to understand metabolic capacities. Carnivores, in general, have low metabolic abilities, making them vulnerable to a variety of chemicals. Raccoons (Procyon lotor) in the wild have been found to have high levels of xenobiotics. However, little is known about the metabolic capacity of the cytochrome P450 (CYP) enzymes in this species. Thus, this study used liver samples to investigate the characteristics of CYP enzymes in wild raccoons. In 22 wild raccoons, CYP concentrations in hepatic microsomes were examined. To better understand the properties of CYP-dependent metabolism, in vitro metabolic activity studies were performed using ethoxyresorufin, pentoxyresorufin and testosterone as substrates. In addition, three raccoons were fed commercial dog food in the laboratory for one week, and the effects on CYP-dependent metabolism were investigated. In comparison to other mammalian species, raccoons had very low concentrations of CYP in their livers. In an in vitro enzymatic analysis, raccoons' ethoxyresorufin O-deethylase (EROD) and pentoxyresorufin O-depentylase (PROD) metabolic capacities were less than one-fifth and one-tenth of rats', respectively. These results indicate the possible high risk in raccoons if exposed to high levels of environmental xenobiotics because of their poor CYP activity. In this study, the features of CYP-dependent metabolism in wild raccoons are described for the first time.
• Duplication, Loss, and Evolutionary Features of Specific UDP-Glucuronosyltransferase Genes in Carnivora (Mammalia, Laurasiatheria).

  Mitsuki Kondo, Yoshinori Ikenaka, Shouta M M Nakayama, Yusuke K Kawai, Mayumi Ishizuka

  Animals : an open access journal from MDPI 12 21 2022年10月27日 

  UDP-glucuronosyltransferases (UGTs) are one of the most important enzymes for xenobiotic metabolism or detoxification. Through duplication and loss of genes, mammals evolved the species-specific variety of UGT isoforms. Among mammals, Carnivora is one of the orders that includes various carnivorous species, yet there is huge variation of food habitat. Recently, lower activity of UGT1A and 2B were shown in Felidae and pinnipeds, suggesting evolutional loss of these isoforms. However, comprehensive analysis for genetic or evolutional features are still missing. This study was conducted to reveal evolutional history of UGTs in Carnivoran species. We found specific gene expansion of UGT1As in Canidae, brown bear and black bear. We also found similar genetic duplication in UGT2Bs in Canidae, and some Mustelidae and Ursidae. In addition, we discovered contraction or complete loss of UGT1A7-12 in phocids, some otariids, felids, and some Mustelids. These studies indicate that even closely related species have completely different evolution of UGTs and further imply the difficulty of extrapolation of the pharmacokinetics and toxicokinetic result of experimental animals into wildlife carnivorans.
• Specific Gene Duplication and Loss of Cytochrome P450 in Families 1-3 in Carnivora (Mammalia, Laurasiatheria).

  Mitsuki Kondo, Yoshinori Ikenaka, Shouta M M Nakayama, Yusuke K Kawai, Mayumi Ishizuka

  Animals : an open access journal from MDPI 12 20 2022年10月18日 

  Cytochrome P450s are among the most important xenobiotic metabolism enzymes that catalyze the metabolism of a wide range of chemicals. Through duplication and loss events, CYPs have created their original feature of detoxification in each mammal. We performed a comprehensive genomic analysis to reveal the evolutionary features of the main xenobiotic metabolizing family: the CYP1-3 families in Carnivora. We found specific gene expansion of CYP2Cs and CYP3As in omnivorous animals, such as the brown bear, the black bear, the dog, and the badger, revealing their daily phytochemical intake as providing the causes of their evolutionary adaptation. Further phylogenetic analysis of CYP2Cs revealed Carnivora CYP2Cs were divided into CYP2C21, 2C41, and 2C23 orthologs. Additionally, CYP3As phylogeny also revealed the 3As' evolution was completely different to that of the Caniformia and Feliformia taxa. These studies provide us with fundamental genetic and evolutionary information on CYPs in Carnivora, which is essential for the appropriate interpretation and extrapolation of pharmacokinetics or toxicokinetic data from experimental mammals to wild Carnivora.
• Sex-specific behavioral effects of acute exposure to the neonicotinoid clothianidin in mice.

  Shizuka Kubo, Tetsushi Hirano, Yuka Miyata, Shuji Ohno, Kanoko Onaru, Yoshinori Ikenaka, Shouta M M Nakayama, Mayumi Ishizuka, Youhei Mantani, Toshifumi Yokoyama, Nobuhiko Hoshi

  Toxicology and applied pharmacology 456 116283 - 116283 2022年10月14日 

  Although neonicotinoids are among the major classes of pesticides that affect mammalian nervous systems, little is known about sex differences in their effects. This study aimed to examine whether the neurobehavioral effects of a neonicotinoid, clothianidin (CLO), differed between sexes. Male and female C57BL/6 N mice were orally administered CLO (5 or 50 mg/kg) at or below the chronic no-observed-adverse-effect-level (NOAEL) and subjected to behavioral tests of emotional and learning functions. Changes in neuroactivity in several brain regions and the concentrations of CLO and its metabolites in blood and urine were measured. Acute CLO exposure caused sex-related behavioral effects; decreases in locomotor activities and elevation of anxiety-like behaviors were more apparent in males than in females. In addition, male-specific impairment of short- and long-term learning memory by CLO exposure was observed in both the novel recognition test and the Barnes maze test. Male-dominant increases in the number of c-fos positive cells were observed in the paraventricular thalamic nucleus in the thalamus and in the dentate gyrus in the hippocampus, which are related to the stress response and learning function, respectively. The concentrations of CLO and most metabolites in blood and urine were higher in males. These results support the notion that male mice are more vulnerable than females to the neurobehavioral effects of CLO and provide novel insights into the risk assessment of neonicotinoids in mammalian neuronal function.
• Methylation profiles of global LINE-1 DNA and the GSTP1 promoter region in children exposed to lead (Pb)

  Yared Beyene Yohannes, Shouta M. M. Nakayama, John Yabe, Haruya Toyomaki, Andrew Kataba, Hokuto Nakata, Kaampwe Muzandu, Chihiro Miyashita, Yoshinori Ikenaka, Kennedy Choongo, Mayumi Ishizuka

  EPIGENETICS 17 13 2377 - 2388 2022年09月 

  Lead (Pb) exposure has adverse health effects and altered DNA methylation may contribute to Pb toxicity. LINE-1 is an interspersed repeated DNA that is used as a surrogate marker for estimating genomic DNA methylation levels, and GSTP1 is an isozyme that detoxifies xenobiotics like Pb, and its expression is inhibited by methylation. Thus, to assess the effects of Pb exposure on global hypomethylation and gene-specific promoter hypermethylation, we examined DNA methylation at LINE-1 repetitive elements and the GSTP1 promoter region. Blood samples were obtained from children (N = 123) living in Pb-polluted areas (as exposed children) and children (N = 63) living in Pb-unpolluted areas (as control children) in Kabwe, Zambia. ICP-MS was used to determine blood lead levels (BLLs), and pyrosequencing and a fluorescence-based polymerase chain reaction assay were used to determine levels of LINE-1 methylation and GSTP1 promoter methylation, respectively. Inverse association was found between BLLs and LINE-1 methylation (beta = - 0.046, p = 0.006). The highest quartile of BLL had significant hypomethylation of LINE-1 (p for trend = 0.03), suggesting the higher the BLL, the lower LINE-1 methylation. GSTP1 methylation levels did not differ significantly between the two areas (p = 0.504), nor was it associated with Pb poisoning risk (OR = 1.03, p = 0.952), indicating GSTP1 methylation may not be a reliable biomarker of Pb exposure in healthy people. Therefore, Pb-related health problems could result from global DNA methylation changes due to high BLLs.
• Toxicokinetic analysis of the anticoagulant rodenticides warfarin and diphacinone in Egyptian fruit bats (Rousettus aegyptiacus) as a comparative sensitivity assessment for Bonin fruit bats (Pteropus pselaphon)

  Kazuki Takeda, Kosuke Manago, Ayuko Morita, Yusuke K. Kawai, Nobuaki Yasuo, Masakazu Sekijima, Yoshinori Ikenaka, Takuma Hashimoto, Ryuichi Minato, Yusuke Oyamada, Kazuo Horikoshi, Hajime Suzuki, Mayumi Ishizuka, Shouta M.M. Nakayama

  Ecotoxicology and Environmental Safety 243 113971 - 113971 2022年09月
• Narrative review of lead poisoning in humans caused by industrial activities and measures compatible with sustainable industrial activities in Republic of Zambia

  Hokuto Nakata, Shouta M.M. Nakayama, John Yabe, Kaampwe Muzandu, Andrew Kataba, Atsuko Ikeda-Araki, Marie-Noel Brune Drisse, Lesley Jayne Onyon, Julia Gorman, Poudel Kritika, Hisanori Fukunaga, Yoshinori Ikenaka, Reiko Kishi, Mayumi Ishizuka

  Science of The Total Environment 157833 - 157833 2022年08月
• Clarifying expression patterns by renal lesion using transcriptome analysis and vanin-1 as a potential novel biomarker for renal injury in chickens.

  Chihiro Ishii, Yusuke K Kawai, Yoshinori Ikenaka, Naoya Maekawa, Osamu Ichii, Shouta M M Nakayama, Mayumi Ishizuka

  Poultry science 101 9 102011 - 102011 2022年06月16日 

  Bird death is often caused by renal lesions induced by chemicals. The avian kidney has a renal portal system with significant blood flow that is sensitive to many chemicals. However, early avian biomarkers for kidney injury are yet to be identified. This study aimed to identify novel renal biomarkers. Acute kidney injury (AKI) can be divided into acute interstitial nephritis (AIN) and acute tubular necrosis (ATN). A chicken model of kidney damage was created by an injection of diclofenac or cisplatin, which caused either AIN or ATN, respectively. Microarray analysis was performed to profile the gene expression patterns in the chickens with nephropathy. A gene enrichment analysis suggested that the genes related to responses to external stimuli showed expression changes in both AIN and ATN. However, hierarchical clustering analyses suggested that gene expression patterns differed between AIN and ATN, and the number of biomarkers relating to renal damage was low. To identify early biomarkers for nephropathy, we focused on genes that were induced at various levels of renal damage. The gene, vanin-1 (VNN1) was highly induced in the early stages of renal damage. A quantitative real-time PCR analysis supported this finding. These results suggest VNN1 could be a useful early biomarker of kidney injury in avian species.
• Cytochrome P450 2J (CYP2J) Genes in Dogs, Cats, and Pigs Are Expressed and Encode Functional Drug-Metabolizing Enzymes.

  Yasuhiro Uno, Norie Murayama, Moe Ijiri, Hiroaki Kawaguchi, Osamu Yamato, Mitsuya Shiraishi, Atsushi Asano, Hiroki Teraoka, Hazuki Mizukawa, Shouta M M Nakayama, Yoshinori Ikenaka, Mayumi Ishizuka, Hiroshi Yamazaki

  Drug metabolism and disposition: the biological fate of chemicals 50 11 1434 - 1441 2022年06月14日 

  Cytochromes P450 (P450 or CYP) have been identified and analyzed in dogs and pigs, species that are often used in preclinical drug studies. Moreover, P450s are clinically important for drug therapy not only in humans but also in species under veterinary care, including dogs and cats. In the present study, seven P450s homologous to human CYP2J2, namely, dog CYP2J2; cat CYP2J2; and pig CYP2J33, CYP2J34, CYP2J35, CYP2J91, and CYP2J93, were newly identified and characterized. The cDNAs of these CYP2Js contained open reading frames of 502 amino acids, except for CYP2J35 (498 amino acids), and shared high sequence identity (77-80%) with human CYP2J2. Phylogenetic analysis revealed that dog and cat CYP2J2 were closely related, whereas pig CYP2Js formed a cluster. All seven CYP2J genes contain nine coding exons and are located in corresponding genomic regions, with the pig CYP2J genes forming a gene cluster. These CYP2J2 mRNAs were predominantly expressed in small intestine with additional expression in kidney and brain for dog CYP2J2 and pig CYP2J91 mRNAs, respectively. All seven CYP2Js metabolized human CYP2J2 substrates terfenadine, ebastine, and astemizole, indicating that they are functional enzymes. Dog CYP2J2 and pig CYP2J34 and CYP2J35 efficiently catalyzed ebastine primary hydroxylation and secondary carebastine formation at low substrate concentrations, just as human CYP2J2 does. Velocity-versus-substate plots exhibited sigmoidal relationships for dog CYP2J2, cat CYP2J2, and pig CYP2J33, indicating allosteric interactions. These results suggest that dog, cat, and pig CYP2Js have similar functional characteristics to human CYP2J2, with slight differences in ebastine and astemizole oxidations. Significance Statement New dog cytochrome P450 2J2 (CYP2J2); cat CYP2J2; and pig CYP2J33, CYP2J34, CYP2J35, CYP2J91, and CYP2J93, homologous to human CYP2J2, were identified and characterized by sequence, phylogenetic, and genomic structure analyses. Intestinal expression patterns of CYP2J mRNAs were characteristic in dogs, cats, and pigs. Dog, cat, and pig CYP2Js likely play roles as drug-metabolizing enzymes in small intestine, similar to human CYP2J2.
• Behavior and toxic effects of Pb in a waterfowl model with oral exposure to Pb shots: Investigating Pb exposure in wild birds.

  Hiroshi Sato, Chihiro Ishii, Shouta M M Nakayama, Takahiro Ichise, Keisuke Saito, Yukiko Watanabe, Kohei Ogasawara, Ryota Torimoto, Atsushi Kobayashi, Takashi Kimura, Yukiko Nakamura, Junya Yamagishi, Yoshinori Ikenaka, Mayumi Ishizuka

  Environmental pollution (Barking, Essex : 1987) 308 119580 - 119580 2022年06月06日 

  Among wild birds, lead (Pb) exposure caused by ingestion of ammunition is a worldwide problem. We aimed to reveal the behavior and toxic effect of Pb caused by ingesting Pb shots in waterfowl. Four male, eight-week old Muscovy ducks (Cairina moschata) were given three Pb shots (approximately 240 mg in total) orally and then fed for 29 days after exposure, simulating a low-dose Pb exposure in wild waterfowl. During the breeding period, blood samples were collected 10 times, and fecal samples every day. Additionally, 22 fresh tissue and 6 bone samples were obtained from each duck through the dissection. Although there were no gross abnormalities, the maximum blood Pb concentration of each duck ranged from 0.6 to 3.7 mg/L, reaching a threshold concentration indicative of clinical symptoms (>0.5 mg/L). δ-aminolevulinic acid dehydratase declined one day after exposure and remained low throughout the feeding period. Hematocrit also tended to decrease, indicating signs of anemia. The highest Pb accumulation was observed in the bones, followed by the kidneys, intestinal tracts, and liver. High Pb accumulation in the bones, which are known to have a long Pb half-life, suggested that Pb would remain in the body and possibly affect bird health beyond 28 days after exposure. Gene expression analysis showed a significant increase in the expression of the toll-like receptor-3 gene, which is involved in virus discrimination in the liver, suggesting a disruption of the immune system. Microbiota analyses showed a correlation between the blood Pb concentration and the abundances of Lachnospiraceae and Ruminococcaceae, suggesting that Pb affects lipid metabolism. These results provide fundamental data on Pb exposure in wild birds and a new perspective on the damage such exposure causes.
• Health impact assessment of pet cats caused by organohalogen contaminants by serum metabolomics and thyroid hormone analysis.

  Kei Nomiyama, Yasuo Yamamoto, Akifumi Eguchi, Hiroyuki Nishikawa, Hazuki Mizukawa, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Shouta M M Nakayama, Yoshinori Ikenaka, Mayumi Ishizuka

  The Science of the total environment 842 156490 - 156490 2022年06月03日 

  Companion animals are in close contact with the human surroundings, and there is growing concern about the effects of harmful substances on the health of pet cats. In this study, we investigated the potential health effects of organohalogen compounds (OHCs) on thyroid hormone (TH) homeostasis and metabolomics in Japanese pet cats. There was a significant negative correlation between concentrations of several contaminants, such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), hydroxylated PCBs (OH-PCBs), hydroxylated PBDEs (OH-PBDEs), and THs in cat serum samples. These results suggested that exposure to OHCs causes a decrease in serum TH levels in pet cats. In this metabolomics study, each exposure level of parent compounds (PCBs and PBDEs) and their hydroxylated compounds (OH-PCBs and OH-PBDEs) were associated with their own unique primary metabolic pathways, suggesting that parent and phenolic compounds exhibit different mechanisms of action and biological effects. PCBs were associated with many metabolic pathways, including glutathione and purine metabolism, and the effects were replicated in in-vivo cat PCB administration studies. These results demonstrated that OHC exposure causes chronic oxidative stress in pet cats. PBDEs were positively associated with alanine, aspartate, and glutamate metabolism. Due to the chronic exposure of cats to mixtures of these contaminants, the combination of their respective metabolic pathways may have a synergistic effect.
• Impacts of Surface Water on Windborne Lead Dispersion from the Zinc Plant Leach Residue in Kabwe, Zambia

  Shinsaku Nakamura, Toshifumi Igarashi, Yoshitaka Uchida, Mayumi Ito, Kazuyo Hirose, Tsutomu Sato, Walubita Mufalo, Meki Chirwa, Imasiku Nyambe, Hokuto Nakata, Shouta Nakayama, Mayumi Ishizuka

  Minerals 12 5 2022年05月 

  Effects of the water content of ground surface on windborne lead (Pb) dispersion from the zinc (Zn) leach residue site at the Kabwe mine, Zambia, were simulated. The Pb-bearing Zn plant leach residue site was selected as the source of the dispersion, and water conditions of the surface of the source were evaluated by the modified normalized difference water index (MNDWI) under the actual weather conditions in the year 2019. The MNDWI was calculated based on Sentinel-2 datasets, which were acquired in the year 2019. The index was used for monitoring the surface condition of the source necessary for simulating Pb dispersion, because the higher surface water content reduces the intensity of windborne source. The results showed that the wind speeds and directions had huge impacts on Pb dispersion when the MNDWI had negative values, and that the dispersion was inhibited when the MNDWI had positive values. These indicate that the water content of the surface is sensitive to dispersion, and that MNDWI is an effective parameter that expresses the source strength.
• Geospatial approach to investigate spatial clustering and hotspots of blood lead levels in children within Kabwe, Zambia.

  Given Moonga, Moses N Chisola, Ursula Berger, Dennis Nowak, John Yabe, Hokuto Nakata, Shouta Nakayama, Mayumi Ishizuka, Stephan Bose-O'Reilly

  Environmental research 207 112646 - 112646 2022年05月01日 

  BACKGROUND: Communities around Kabwe, Zambia are exposed to lead due to deposits from an old lead (Pb) and zinc (Zn) mining site. Children are particularly more vulnerable than adults, presenting with greatest risk of health complications. They have increased oral uptake due to their hand to mouth activities. Spatial analysis of childhood lead exposure is useful in identifying specific areas with highest risk of pollution. The objective of the current study was to use a geospatial approach to investigate spatial clustering and hotspots of blood lead levels in children within Kabwe. METHODS: We analysed existing data on blood lead levels (BLL) for 362 children below the age of 15 from Kabwe town. We used spatial autocorrelation methods involving the global Moran's I and local Getis-Ord Gi*statistic in ArcMap 10.5.1, to test for spatial dependency among the blood lead levels in children using the household geolocations. RESULTS: BLL in children from Kabwe are spatially autocorrelated with a Moran's Index of 0.62 (p < 0.001). We found distinct hotspots (mean 51.9 μg/dL) in communities close to the old lead and zinc-mining site, lying on its western side. Whereas coldspots (mean 7 μg/dL) where observed in areas distant to the mine and traced on the eastern side. This pattern suggests a possible association between observed BLL and distance from the abandoned lead and zinc mine, and prevailing winds. CONCLUSION: Using geocoded data for households, we found clustering of childhood blood lead and identified distinct hotspot areas with high lead levels for Kabwe town. The geospatial approach used is especially valuable in resource-constrained settings like Zambia, where the precise identification of high risk locations allows for the initiation of targeted remedial and treatment programs.
• Estimation of the Effects of Neonicotinoid Insecticides on Wild Raccoon, Procyon lotor, in Hokkaido, Japan: Urinary Concentrations and Ability for Hepatic Metabolism of Neonicotinoids.

  So Shinya, Mariko Sashika, Miku Minamikawa, Tetsuji Itoh, Yared Beyene Yohannes, Shouta M M Nakayama, Mayumi Ishizuka, Collins Nimako, Yoshinori Ikenaka

  Environmental toxicology and chemistry 41 8 1865 - 1874 2022年04月22日 

  Toxicological effects of NNIs have been reported for mammals, such as humans, rats, and mice. However, there are limited reports on their toxic effects on wild mammals. To predict NNI-induced toxic effects on wild mammals, it is necessary to determine the exposure levels and metabolic ability of these species. We considered that raccoons could be an animal model for evaluating NNIs-induced toxicities on wildlife as they inhabit near agricultural fields and eat crops treated with NNIs. The objective of this study was to estimate the effects of NNIs exposure on wild raccoons. Urinary concentrations of NNI compounds (n=59) and cytochrome P450-dependent metabolism of NNIs (n=3) were evaluated in wild raccoons captured in Hokkaido, Japan, in 2020. We detected either of the six NNIs or one metabolite, including acetamiprid, imidacloprid, clothianidin, dinotefuran, thiacloprid, thiamethoxam, and desmethyl-acetamiprid in 90% of raccoons (53/59); the average cumulative concentration of the 7 NNI compounds was 3.1 ng/mL. The urinary concentrations were not much different from those reported previously for humans. Furthermore, we performed an in vitro assessment of the ability of raccoons to metabolize NNIs using hepatic microsomes. The amounts of NNI metabolites were measured using LC/ESI/MS/MS and compared with those in rats. Raccoons showed much lower metabolic ability; the Vmax /Km values for raccoons were 1/10 to 1/3 of those for rats. For the first time, we show wild raccoons could be frequently exposed to NNIs in the environment, and the cytochrome P450-dependent metabolism of NNIs in the livers of raccoons might be low. This study would contribute to better understandings of the effects of NNIs on raccoons, leading to better conservation efforts for wild mammals. This article is protected by copyright. All rights reserved. © 2022 SETAC.
• Human Health Risk Assessment from Lead Exposure through Consumption of Raw Cow Milk from Free-Range Cattle Reared in the Vicinity of a Lead-Zinc Mine in Kabwe.

  Golden Zyambo, John Yabe, Kaampwe Muzandu, Ethel M'kandawire, Kennedy Choongo, Andrew Kataba, Kenneth Chawinga, Allan Liazambi, Shouta M M Nakayama, Hokuto Nakata, Mayumi Ishizuka

  International journal of environmental research and public health 19 8 2022年04月14日 

  Lead (Pb) contamination in the environment affects both humans and animals. Chronic exposure to Pb via dietary intake of animal products such as milk from contaminated areas poses a health risk to consumers; therefore, the present study investigated Pb contamination in cow milk and its health risk impact on humans through consumption of milk from cattle reared in the proximity of a Pb-Zn mine in Kabwe, Zambia. Fresh milk samples were collected from cows from Kang'omba (KN), Kafulamse (KF), Mpima (MP), Mukobeko (MK), and Munga (MN) farming areas. Pb determination was performed using Graphite Flame Absorption Atomic Spectrophotometry (GFAAS). Cow milk Pb levels showed different concentration patterns according to season, distance, and location of the farms from the Pb-Zn mine. The overall mean Pb levels were ranged 0.60-2.22 µg/kg and 0.50-4.24 µg/kg in the wet and dry seasons, respectively. The mean Pb concentration, chronic daily intake (CDIs), target hazard quotients (THQs), and incremental lifetime cancer risk (ILCR) results obtained were all within the permissible limits of 20 µg/kg, 3 and 12.5 µg/kg-BW/day, <1 and 10-4 to10-6, respectively. In conclusion, although Pb was detected in milk from cows reared in Kabwe, the health risk effects of Pb exposure associated with the consumption of milk in both adults and children were negligible.
• Alkaline Leaching and Concurrent Cementation of Dissolved Pb and Zn from Zinc Plant Leach Residues

  Marthias Silwamba, Mayumi Ito, Naoki Hiroyoshi, Carlito Baltazar Tabelin, Ryota Hashizume, Tomoki Fukushima, Ilhwan Park, Sanghee Jeon, Toshifumi Igarashi, Tsutomu Sato, Imasiku Nyambe, Hokuto Nakata, Shouta Nakayama, Mayumi Ishizuka

  Minerals 12 4 2022年04月 

  Zinc plant leach residues (ZPLRs), particularly those produced using old technologies, have both economic importance as secondary raw materials and have environmental impacts because they contain hazardous heavy metals that pose risks to human health and the environment. Therefore, the extraction and recovery of these metals from ZPLRs has both economic and environmental benefits. In this study, we investigated the removal of lead (Pb) and zinc (Zn) from ZPLRs by alkaline (NaOH) leaching and the concurrent cementation of dissolved Pb and Zn using aluminum (Al) metal powder. The effects of the leaching time, NaOH concentration, solid-to-liquid ratio (S/L), and dosage of Al metal powder on the extraction of Pb and Zn were investigated. Pb and Zn removal efficiencies increased with increasing NaOH concentrations and decreasing S/Ls. The Pb and Zn removal efficiencies were 62.2% and 27.1%, respectively, when 2.5 g/50 mL (S/L) of ZPLRs were leached in a 3 M NaOH solution for 30 min. The extraction of Pb and Zn could be attributed to the partitioning of these metals in relatively more mobile phases—water-soluble, exchangeable, and carbonate phases— in ZPLRs. Around 100% of dissolved Pb and less than 2% of dissolved Zn were cemented in leaching pulp when Al metal powder was added. Minerals in the solid residues, particularly iron oxides minerals, were found to suppress the cementation of extracted Zn in leaching pulp, and when they were removed by filtration, Zn was recovered by Al metal powder via cementation.
• Geochemical identification of particulate lead pollution in shallow groundwater in inhabited areas in Kabwe, Zambia

  Kazuhiro Toyoda, Shota Nakano, Shunitz Tanaka, Kawawa Banda, Imasiku A. Nyambe, Tsuyoshi Ishikawa, Shouta Nakayama, Mayumi Ishizuka

  Applied Geochemistry 139 105215 - 105215 2022年04月
• Assessment of ameliorative effects of organic dietary interventions on neonicotinoid exposure rates in a Japanese population.

  Collins Nimako, Takahiro Ichise, Hiroshi Hasegawa, Osei Akoto, Nathaniel O Boadi, Kumiko Taira, Kazutoshi Fujioka, Norikazu Isoda, Shouta M M Nakayama, Mayumi Ishizuka, Yoshinori Ikenaka

  Environment international 162 107169 - 107169 2022年04月 

  Neonicotinoid insecticides (NNIs) are a popular class of insecticides used in various pest management regimens worldwide. Biomonitoring studies continuously report high exposure rates of NNIs in various human populations across the globe. Yet, there is no validated countermeasure for combating the recent exponential rise in NNI exposure rates observed in human populations. The current study assessed the impacts of organic dietary interventions on NNI exposure rates in a Japanese population. A total of 103 volunteers were recruited into the study. Subjects were either served with Organic diets for 5 and 30 days or conventional diets. A total of 919 repeated urine samples were collected from the participants and then subjected to LC-MS/MS analysis to determine urinary concentrations of 7 NNIs parent compounds and an NNI metabolite. Eight NNIs were detected; with a decreasing detection frequency (%Dfs) pattern; desmethyl-acetamiprid (dm-ACE) (64.96%) > dinotefuran (52.12%), imidacloprid (39.61%) > clothianidin (33.95%) > thiamethoxam (28.51%) > acetamiprid (12.62%) > nitenpyram (5.33%) > thiacloprid (2.83%). Dinotefuran, dm-ACE, and clothianidin recorded the highest concentrations in the subjects. The %Df of NNIs in the 5-days or 30-days organic diet group were lower than those of the conventional diet consumers. The organic diet group showed lower rates of multiple NNI exposures than those of the conventional diet consumers. The mean and median cumulative levels of NNIs (median IMIeq) were significantly lower in the organic diet group than the conventional diet group (p < 0.0001). The estimated daily intakes (EDIs) of NNIs were higher in adults than children, but less than 1% of NNI cRfDs, except for clothianidin, which exhibited a %cRfD of 1.32 in children. Compared to the conventional diet group, the 5- and 30-day organic dietary intervention showed drastic reductions in NNI EDIs. Findings from the present study give credence to organic dietary interventions as potential ameliorative strategies for NNI exposure rates in human populations.
• Ca2+ imaging with two-photon microscopy to detect the disruption of brain function in mice administered neonicotinoid insecticides.

  Anri Hirai, Shouta Sugio, Collins Nimako, Shouta M M Nakayama, Keisuke Kato, Keisuke Takahashi, Koji Arizono, Tetsushi Hirano, Nobuhiko Hoshi, Kazutoshi Fujioka, Kumiko Taira, Mayumi Ishizuka, Hiroaki Wake, Yoshinori Ikenaka

  Scientific reports 12 1 5114 - 5114 2022年03月24日 

  Neonicotinoid pesticides are a class of insecticides that reportedly have harmful effects on bees and dragonflies, causing a reduction in their numbers. Neonicotinoids act as neuroreceptor modulators, and some studies have reported their association with neurodevelopmental disorders. However, the precise effect of neonicotinoids on the central nervous system has not yet been identified. Herein, we conducted in vivo Ca2+ imaging using a two-photon microscope to detect the abnormal activity of neuronal circuits in the brain after neonicotinoid application. The oral administration of acetamiprid (ACE) (20 mg/kg body weight (BW) in mature mice with a quantity less than the no-observed-adverse-effect level (NOAEL) and a tenth or half of the median lethal dose (LD50) of nicotine (0.33 or 1.65 mg/kg BW, respectively), as a typical nicotinic acetylcholine receptor (nAChR) agonist, increased anxiety-like behavior associated with altered activities of the neuronal population in the somatosensory cortex. Furthermore, we detected ACE and its metabolites in the brain, 1 h after ACE administration. The results suggested that in vivo Ca2+ imaging using a two-photon microscope enabled the highly sensitive detection of neurotoxicant-mediated brain disturbance of nerves.
• Foraging ecology of mature male Antarctic minke whales (Balaenoptera bonaerensis) revealed by stable isotope analysis of baleen plates

  Hiroshi Ishikawa, Mayuko Otsuki, Tsutomu Tamura, Kenji Konishi, Takaharu Bando, Mayumi Ishizuka, Yoshinori Ikenaka, Shouta M.M. Nakayama, Yoko Mitani

  Polar Science 31 2022年03月 

  The Antarctic minke whale (Balaenoptera bonaerensis) is a seasonal migrator that feeds mainly on Antarctic krill at higher latitudes during the summer and travels to lower latitudes to breed in winter. A previous study using δ13C and δ15N values of baleen plates showed that pregnant Antarctic minke whales feed on Antarctic krill in the foraging season, with less feeding during the breeding season. However, long-term changes in the habitat use and diet of males remain unknown. In this study, we estimated the foraging habits of nine mature male Antarctic minke whales using the stable isotope signatures of baleen plates. From Bayesian stable isotope mixing models, it was found that Antarctic krill was the predominant prey of male whales, and prey species in lower latitudes were rarely incorporated into the baleen plates. This result is consistent with that of female Antarctic minke whales. Eight whales showed at least one oscillation in δ13C and δ15N values, whereas one whale (AM246) showed no variation in δ15N values. This possibly indicates that AM246 remained in the Antarctic water year-round. Our results suggest multiple migration patterns of male Antarctic minke whales.
• Environmentally relevant lead (Pb) water concentration induce toxicity in zebrafish (Danio rerio) larvae.

  Andrew Kataba, Tarryn L Botha, Shouta M M Nakayama, Yared B Yohannes, Yoshinori Ikenaka, Victor Wepener, Mayumi Ishizuka

  Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 252 109215 - 109215 2022年02月 

  Early developmental stages of aquatic organisms including fish are inherently vulnerable to lead (Pb) and other water metal contaminants. However, reports on the deleterious effects of environmentally relevant Pb levels are limited. To this end, we exposed 2.5 h post fertilization (hpf) old zebrafish (Danio rerio) embryos to a range of Pb concentrations encompassing environmentally relevant levels (1, 10, 25, 50 and 100 μg/L Pb) until 96 hpf. Exposure negatively impacted the development and survival of zebrafish embryos by inducing embryo coagulation related mortalities in a concentration-dependent manner. At 24 hpf, the highest level of exposure (100 μg/L Pb) had impaired embryo activity characterized by reduced burst activity and the number of movements per minute made by embryos. At 72 hpf, newly hatched larvae exhibited adverse cardiovascular effects (100 μg/L Pb group) and neuromuscular effects (50 and 100 μg/L Pb groups). The antioxidant system dysregulation evidenced by downregulation of catalase, and upregulation of mRNA expression of glutathione S-transferase and cytochrome oxidase subunit I were observed. The pro-apoptotic tumour protein P53 (TP53) and the anti-apoptotic B cell lymphoma -2 (Bcl-2) mRNA expression levels were also affected. The former was downregulated across exposed groups and the latter was upregulated and downregulated in the groups with Pb concentrations less than 50 μg/L Pb and downregulated in 50 μg/L Pb, respectively. These findings suggest that Pb within environmentally relevant levels may be deleterious to developing zebrafish.
• Metabolomic Alteration in the Plasma of Wild Rodents Environmentally Exposed to Lead: A Preliminary Study.

  Hokuto Nakata, Akifumi Eguchi, Shouta M M Nakayama, John Yabe, Kaampwe Muzandu, Yoshinori Ikenaka, Chisato Mori, Mayumi Ishizuka

  International journal of environmental research and public health 19 1 2022年01月04日 

  Lead poisoning is often considered a traditional disease; however, the specific mechanism of toxicity remains unclear. The study of Pb-induced alterations in cellular metabolic pathways is important to understand the biological response and disorders associated with environmental exposure to lead. Metabolomics studies have recently been paid considerable attention to understand in detail the biological response to lead exposure and the associated toxicity mechanisms. In the present study, wild rodents collected from an area contaminated with lead (N = 18) and a control area (N = 10) were investigated. This was the first ever experimental metabolomic study of wildlife exposed to lead in the field. While the levels of plasma phenylalanine and isoleucine were significantly higher in a lead-contaminated area versus the control area, hydroxybutyric acid was marginally significantly higher in the contaminated area, suggesting the possibility of enhancement of lipid metabolism. In the interregional least-absolute shrinkage and selection operator (lasso) regression model analysis, phenylalanine and isoleucine were identified as possible biomarkers, which is in agreement with the random forest model. In addition, in the random forest model, glutaric acid, glutamine, and hydroxybutyric acid were selected. In agreement with previous studies, enrichment analysis showed alterations in the urea cycle and ATP-binding cassette transporter pathways. Although regional rodent species bias was observed in this study, and the relatively small sample size should be taken into account, the present results are to some extent consistent with those of previous studies on humans and laboratory animals.
• Estimation of the reference lead (Pb) concentration levels affecting immune cells in the blood of Black-headed Gulls (Chroicocephalus ridibundus, Laridae)

  Nana Ushine, Osamu Kurata, Yoshikazu Tanaka, Shouta M.M Nakayama, Mayumi Ishizuka, Takuya Kato, Shin-Ichi Hayama

  Avian Conservation and Ecology 17 2 2022年
• A GCDGC-specific DNA (cytosine-5) methyltransferase that methylates the GCWGC sequence on both strands and the GCSGC sequence on one strand.

  Yoshikazu Furuta, Fumihito Miura, Takahiro Ichise, Shouta M M Nakayama, Yoshinori Ikenaka, Tuvshinzaya Zorigt, Mai Tsujinouchi, Mayumi Ishizuka, Takashi Ito, Hideaki Higashi

  PloS one 17 3 e0265225  2022年 

  5-Methylcytosine is one of the major epigenetic marks of DNA in living organisms. Some bacterial species possess DNA methyltransferases that modify cytosines on both strands to produce fully-methylated sites or on either strand to produce hemi-methylated sites. In this study, we characterized a DNA methyltransferase that produces two sequences with different methylation patterns: one methylated on both strands and another on one strand. M.BatI is the orphan DNA methyltransferase of Bacillus anthracis coded in one of the prophages on the chromosome. Analysis of M.BatI modified DNA by bisulfite sequencing revealed that the enzyme methylates the first cytosine in sequences of 5'-GCAGC-3', 5'-GCTGC-3', and 5'-GCGGC-3', but not of 5'-GCCGC-3'. This resulted in the production of fully-methylated 5'-GCWGC-3' and hemi-methylated 5'-GCSGC-3'. M.BatI also showed toxicity when expressed in E. coli, which was caused by a mechanism other than DNA modification activity. Homologs of M.BatI were found in other Bacillus species on different prophage like regions, suggesting the spread of the gene by several different phages. The discovery of the DNA methyltransferase with unique modification target specificity suggested unrevealed diversity of target sequences of bacterial cytosine DNA methyltransferase.
• Glutathione S-transferase gene polymorphisms in association with susceptibility to lead toxicity in lead- and cadmium-exposed children near an abandoned lead-zinc mining area in Kabwe, Zambia.

  Yared Beyene Yohannes, Shouta M M Nakayama, John Yabe, Haruya Toyomaki, Andrew Kataba, Hokuto Nakata, Kaampwe Muzandu, Yoshinori Ikenaka, Kennedy Choongo, Mayumi Ishizuka

  Environmental science and pollution research international 29 5 6622 - 6632 2022年01月 

  Interindividual genetic variations determine human's susceptibility to heavy metal-induced toxicity. Thus, we analyzed blood concentrations of lead (Pb) and cadmium (Cd) in 140 lead-exposed children. Genotyping of the glutathione S-transferase (GST) genes, GSTM1, GSTT1, and GSTP1 genes, was carried out to investigate their possible association with heavy metal concentrations and the risk of susceptibility to Pb toxicity. Exposure to both heavy metals was prevalent among the children. The blood Pb level ranged from 3.30 to 74.0 μg dL-1 with an average value of 26.8 μg dL-1 that is five times above its reference level. The average Cd level (0.22 μg L-1) was below its reference level. The metal-gene interaction showed positive correlation between GSTT1 null genotype and Pb and Cd levels (β = 0.11; p = 0.02 and β = 0.10; p = 0.01, respectively). More pronounced effects (β = 0.19; p < 0.01 and β = 0.25; p = 0.04) were found for the mixture of the three putative genes with blood Pb concentration. The susceptibility analysis using 10 μg dL-1 as blood Pb cutoff level showed a high risk of Pb toxicity (OR = 2.54; 95% CI: 1.02-6.32, p = 0.04) for children carrying the GSTP1 Ile/Val genotype. Further, the combined effect of GSTP1 Ile/Val with GSTT1 null genotype was more pronounced and showed an increased risk of susceptibility to Pb toxicity (OR = 11.7; 95% CI: 1.36-102.1, p = 0.02). In summary, this study suggests that GSTT1 null and GSTP1 Ile/Val genotypes are the main genetic factors, and individual and specific combinations of GSTP1 Ile/Val with GSTM1 and GSTT1 GST polymorphisms are associated with susceptibility to Pb toxicity.
• Effects of zinc on tissue uptake and toxicity of lead in Sprague Dawley rat.

  Andrew Kataba, Shouta M M Nakayama, Yared Beyene Yohannes, Haruya Toyomaki, Hokuto Nakata, Yoshinori Ikenaka, Mayumi Ishizuka

  The Journal of veterinary medical science 83 11 1674 - 1685 2021年10月31日 

  Lead (Pb) exposure occurs together with other metals including zinc (Zn). This study investigated the impact of Zn on Pb tissue accumulation and Pb-induced toxicities. Animals (n = 6 rats per group) were exposed to lead acetate (PbAc) or a combination of PbAc and zinc acetate (ZnAc) under the following groups: control (deionized water), low PbAc [12 mg/kg PbAc (3 mg PbAc/rat/day)], low PbAc-ZnAc [12 mg/kg PbAc (3 mg PbAc/rat/day) + 0.2 mg ZnAc/rat/48 hr], high PbAc [120 mg/kg (30 mg PbAc/rat/day)], and high PbAc-ZnAc [120 mg/kg (30 mg PbAc/rat/day) + 1 mg ZnAc/rat/48 hr] for 8 weeks. A significant reduction in body weight gain was observed in the high PbAc group relative to the control group. Muscles and testes both had reduced and increased Pb uptake in low PbAc-ZnAc and high PbAc-ZnAc groups compared to PbAc only groups, respectively. Bone Pb levels in the high PbAc-ZnAc group were lower than the high PbAc group. Zinc co-administration attenuated Pb-induced inhibition of delta aminolaevulinic acid dehydratase enzyme and enhanced catalase enzyme activity at a high level of exposure. Moreover, ZnAc seems to have minimized the effects of Pb-induced mRNA dysregulation in antioxidant and antiapoptotic enzymes encoding genes. Heme oxygenase-1 was downregulated in the kidney and brain in the low PbAc group. Liver glutathione peroxidase and thioredoxin reductase-1 were downregulated in the high PbAc group. These findings suggest that zinc co-administration with lead may partially mitigate against Pb-induced toxicities.
• Simultaneous steroids measurement in dogs with hyperadrenocorticism using a column-switching liquid chromatography-tandem mass spectrometry method.

  Noboru Sasaki, Thandar Oo, Yoshikazu Yasuda, Takahiro Ichise, Noriyuki Nagata, Nozomu Yokoyama, Kazuyoshi Sasaoka, Keitaro Morishita, Shouta Mm Nakayama, Mayumi Ishizuka, Kensuke Nakamura, Mitsuyoshi Takiguchi, Yoshinori Ikenaka

  The Journal of veterinary medical science 83 11 1634 - 1642 2021年10月31日 

  We developed an analytical method using an on-line column-switching liquid chromatography with triple quadrupole mass spectrometry (LC/MS/MS) for quantifying multiple steroids in serum. Using the developed method, we evaluated the serum concentration of nine steroids (cortisol, corticosterone, cortisone, 11-deoxycortisol, 21-deoxycortisol, deoxycorticosterone, progesterone, 17α-OH-progesterone and aldosterone) in dogs with hyperadrenocorticism (HAC). Serum was mixed with stable isotope internal standards and thereafter purified by the automated column-switching system. The limit of detection ranged 2-16 pg/ml for nine steroids. In the baseline samples, five steroids (cortisol, corticosterone, cortisone, 11-deoxycortisol, and 17α-OH-progesterone) were detected in all dogs. The concentrations of cortisone, 11-deoxycortisol, and 17α-OH-progesterone in dogs with HAC (n=19) were significantly higher those in dogs without HAC (n=15, P<0.02). After the adrenocorticotropic hormone stimulation test, six steroids (cortisol, corticosterone, cortisone, 11-deoxycortisol, 17α-OH-progesterone, and deoxycorticosterone) were above the limit of quantification in all dogs. Cortisol, corticosterone, cortisone, and deoxycorticosterone concentrations of dogs with HAC were significantly higher than those of dogs without HAC (P<0.02). In addition, 11-deoxycortisol and 17α-OH-progesterone concentration was higher in dogs with HAC than in dogs without HAC (P=0.044 and P=0.048, respectively). The on-line column-switching LC/MS/MS would be feasible for measuring multiple steroids in dog serum. The results suggest that cortisone, 11-deoxycortisol, and 17α-OH-progesterone would be related to HAC. Further studies are warranted to assess the clinical feasibility of steroid profile in dogs with HAC.
• Solid-Phase Partitioning and Leaching Behavior of Pb and Zn from Playground Soils in Kabwe, Zambia.

  Walubita Mufalo, Pawit Tangviroon, Toshifumi Igarashi, Mayumi Ito, Tsutomu Sato, Meki Chirwa, Imasiku Nyambe, Hokuto Nakata, Shouta Nakayama, Mayumi Ishizuka

  Toxics 9 10 2021年10月04日 

  Zambia's Kabwe mine wastes (KMWs) are responsible for contaminating the surrounding soil and dust in the Kabwe district. Unfortunately, these wastes arise from the historical mining activities of lead (Pb) and Zinc (Zn), which lacked adequate waste management strategies. As a result, potentially toxic elements (PTEs) (Pb and Zn) spread across the Kabwe district. To assess the soil pollution derived from previous mining activities, we studied topsoil samples (n = 8) from the school playground soils (SPs). In this study, the degree of contamination, geochemical partitioning, and leachability, coupled with the release and retention of Pb and Zn, were studied. The SPs were classified as extremely enriched (EF > 40) and contaminated with Pb (Igeo > 5). On average, Pb (up to 89%) and Zn (up to 69%) were bound with exchangeable, weak acid-soluble, reducible and oxidizable phases, which are considered as 'geochemically mobile' phases in the environment. The leachates from the soils (n = 5) exceeded the Zambian standard (ZS: 190:2010) for Pb in potable drinking water (Pb < 0.01 mg/L). Furthermore, the spatial distribution of Pb and Zn showed a significant reduction in contents of Pb and Zn with the distance from the mine area.
• Lead concentrations and isotope ratios in blood, breastmilk and feces: contribution of both lactation and soil/dust exposure to infants in a lead mining area, Kabwe, Zambia.

  Haruya Toyomaki, John Yabe, Shouta M M Nakayama, Yared B Yohannes, Kaampwe Muzandu, Tiza Mufune, Hokuto Nakata, Yoshinori Ikenaka, Takeshi Kuritani, Mitsuhiro Nakagawa, Kennedy Choongo, Mayumi Ishizuka

  Environmental pollution (Barking, Essex : 1987) 286 117456 - 117456 2021年10月01日 

  Lead (Pb) poses a serious public health concern. Breastmilk may be a possible source of Pb exposure in infants, as Pb can be transferred from the maternal blood to breastmilk. The present study was undertaken to determine the Pb exposure and the contribution of lactation as one of the exposure pathways to infants in a Pb mining area, Kabwe, Zambia. Blood, breastmilk and infants' feces were collected from 418 pairs of infants and mothers. The Pb concentrations, isotope ratios in the samples, and biochemistry in mothers' plasma were analyzed. The overall mean of blood lead levels (BLLs) in infants and mothers were 18.0 and 11.3 μg/dL, respectively. High Pb concentration in breastmilk (range: 0.4-51.9, mean: 5.3 μg/L) above the WHO acceptable level between 2 and 5 μg/L were found and could be one of the sources of Pb exposure in infants. The Pb isotope ratios in infants' feces were the most similar to Pb ratios in the soil samples. The results suggest that infants are also exposed to Pb from the environment. Pb exposure in infants through breastfeeding and soil ingestion could potentially exceed daily intake of Pb which causes neurodevelopmental toxicity. In contrast to the high BLLs in mothers, the plasma biochemical profiles of most analyzed parameters were interestingly within, or close to, the standard reference values. Our data suggest that environmental remediation is urgently needed to reduce the Pb exposure in infants and mothers from the environment in Kabwe in parallel with chelation therapy.
• Cushing症候群と肝細胞癌を合併した犬におけるステロイド値の包括的解析(Comprehensive analysis of steroid profile in dogs with Cushing' syndrome and hepatocellular carcinoma)

  Oo Thandar, 佐々木 東, 池中 良徳, 永田 矩之, 一瀬 貴大, Bin Teoh Yong, 川元 誠, 小島 一輝, 菅原 芽伊, 中山 翔太, 石塚 真由美, 中村 健介, 滝口 満喜

  日本獣医学会学術集会講演要旨集 164回 [HSO - 18] 2021年09月
• Geolocators link marine mercury with levels in wild seabirds throughout their annual cycle: Consequences for trans-ecosystem biotransport.

  Akiko Shoji, Kyle H Elliott, Yutaka Watanuki, Niladri Basu, Shannon Whelan, Joshua Cunningham, Scott Hatch, Hazuki Mizukawa, Shouta M M Nakayama, Yoshinori Ikenaka, Mayumi Ishizuka, Stéphane Aris-Brosou

  Environmental pollution (Barking, Essex : 1987) 284 117035 - 117035 2021年09月01日 

  Seabirds are widely used as indicators of marine pollution, including mercury (Hg), because they track contaminant levels across space and time. However, many seabirds are migratory, and it is difficult to understand the timing and location of their Hg accumulation. Seabirds may obtain Hg thousands of kilometers away, during their non-breeding period, and deposit that Hg into their terrestrial breeding colonies. We predicted that Hg concentration in rectrices reflects exposure during the previous breeding season, in body feathers reflects non-breeding exposure, and in blood collected during breeding reflects exposure during current breeding. To test this hypothesis, we measured total Hg concentration in these three tissues, which reflect different timepoints during the annual cycle of rhinoceros auklets (Cerorhinca monocerata) breeding on both sides of the North Pacific (Middleton Island in Alaska and Teuri Island in Hokkaido), and tracked their wintering movement patterns with biologging devices. We (i) identify the wintering patterns of both populations, (ii) examine Hg levels in different tissues representing exposure at different time periods, (iii) test how environmental Hg exposure during the non-breeding season affects bird contamination, and (iv) assess whether variation in Hg levels during the non-breeding season influences levels accumulated in terrestrial plants. Individuals from both populations followed a figure-eight looping migration pattern. We confirm the existence of a pathway from environmental Hg to plant roots via avian tissues, as Hg concentrations were higher in plants within the auklet colonies than at control sites. Hg concentrations of breast feathers were higher in Alaskan than in Japanese auklets, but Hg concentrations in rectrices and blood were similar. Moreover, we found evidence that tissues with different turnover rates could record local anthropogenic Hg emission rates of areas visited during winter. In conclusion, Hg was transported across thousands of kilometers by seabirds and transferred to local plants.
• Simultaneous quantification of imidacloprid and its metabolites in tissues of mice upon chronic low-dose administration of imidacloprid.

  Collins Nimako, Yoshinori Ikenaka, Osei Akoto, Kazutoshi Fujioka, Kumiko Taira, Koji Arizono, Keisuke Kato, Keisuke Takahashi, Shouta M M Nakayama, Takahiro Ichise, Mayumi Ishizuka

  Journal of chromatography. A 1652 462350 - 462350 2021年08月30日 

  This study aimed to (i) develop a sensitive method for simultaneous detection and quantification of imidacloprid (IMI) and seven of its metabolites in tissue specimens, and to (ii) determine the biodistribution of the IMI compounds in tissues of C57BL/6J male mice; after exposure to 0.6 mg/kg bw/day of IMI (10% of no observable adverse effect level of IMI) through a powdered diet for 24 weeks. We successfully developed a method which was accurate (recoveries were ≥ 70% for most compounds), sensitive (LODs ≤ 0.47 ng/mL and LOQs ≤ 1.43 ng/mL were recorded for all detected compounds, R2 ≥ 0.99) and precise (RSDs ≤ 20%) for routine analysis of IMI and seven of its metabolites in blood and various tissue matrices. After bio-distributional analysis, IMI and five of its metabolites were detected in mice. Brain, testis, lung, kidney, inguinal white adipose tissue and gonadal white adipose tissue mainly accumulated IMI, blood and mesenteric white adipose tissue mainly accumulated IMI-olefin; liver mainly accumulated desnitro-IMI; pancreas predominately accumulated 4-hydroxy-IMI. The desnitro-dehydro-IMI and the desnitro-IMI metabolites recorded tissue-blood concentration ratios ≥ 1.0 for testis, brain, lung and kidney. The cumulative levels of the six detected IMI compounds (Σ6 IMI compounds) were found in the decreasing order: blood > testis > brain > kidney > lung > iWAT > gWAT > mWAT > liver > pancreas. Altogether, this study provided essential data needed for effective mechanistic elucidation of compound-specific adverse outcomes associated with chronic exposures to IMI in mammalian species.
• Evaluation of Dispersion of Lead-Bearing Mine Wastes in Kabwe District, Zambia

  Shinsaku Nakamura, Toshifumi Igarashi, Yoshitaka Uchida, Mayumi Ito, Kazuyo Hirose, Tsutomu Sato, Walubita Mufalo, Meki Chirwa, Imasiku Nyambe, Hokuto Nakata, Shouta Nakayama, Mayumi Ishizuka

  MINERALS 11 8 2021年08月 

  Dispersion of lead (Pb) in mine wastes was simulated for reproducing Pb contamination of soil in Kabwe District, Zambia. Local weather data of year 2019 were monitored in situ and used for the simulations. The plume model, weak puff model, and no puff model were adopted for calculation of Pb dispersion under different wind conditions. The results showed that Pb dispersion from the Kabwe mine was directly affected by wind directions and speeds in the dry season, although it was not appreciably affected in the rainy season. This may be because the source strength is lower in the rainy season due to higher water content of the surface. This indicates that Pb dispersion patterns depend on the season. In addition, the distribution of the amount of deposited Pb-bearing soils around the mine corresponded to the distribution of Pb contents in soils. These results suggest that Pb contamination in soils primarily results from dispersion of fine mine wastes.
• Human Exposures to Neonicotinoids in Kumasi, Ghana.

  Collins Nimako, Yoshinori Ikenaka, Osei Akoto, Nesta Bortey-Sam, Takahiro Ichise, Shouta M M Nakayama, Kwadwo A Asante, Kazutoshi Fujioka, Kumiko Taira, Mayumi Ishizuka

  Environmental toxicology and chemistry 40 8 2306 - 2318 2021年08月 

  Neonicotinoid insecticides (NNIs) are now popular in many agricultural systems across Africa; however, the extent of human exposures to NNIs in African countries is scarcely reported. The present study evaluates neonicotinoid exposures in the consumer population of Kumasi, a cosmopolitan city in Ghana. A total of 75 human urine samples were collected from healthy volunteers (nonfarmers, aged 13-80 yr) and analyzed with a liquid chromatography electrospray ionization tandem mass spectrometry system. Seven NNIs and 3 NNI metabolites were detected in the following pattern (frequency, median concentration, maximum concentration): N-dm-acetamiprid (94.7%, 0.41 µg/L, 8.79 µg/L) > imidacloprid (70.7%, 0.15 µg/L, 211.62 µg/L) > N-(6-chloro-3-pyridylmethyl)-N-ethyl-N'-methylformamidine (62.2%, 0.43 µg/L, 53.85 µg/L) > 2-[N-(6-chloro-3-pyridylmethyl)-N-ethylamino]-2-(methylimino)acetic acid (56.8%, 0.10 µg/L, 3.53 µg/L) > clothianidin (40%, >limit of quantification [LOQ], 0.45 µg/L) > nitenpyram (18.7%, >LOQ, 0.14 µg/L) ≈ thiamethoxam (18.7%, >LOQ, 0.21 µg/L) > dinotefuran (12.0%, >LOQ, 1.01 µg/L) > acetamiprid (2.7%, >LOQ, 0.08 µg/L) ≈ thiacloprid (2.7%, >LOQ, 0.14 µg/L). Approximately 92% of the subjects were found to be exposed to multiple neonicotinoids simultaneously. The mean, median, and maximum imidacloprid equivalent of the relative potency factor of NNIs were found to be 1.6, 0.5, and 22.52, respectively. The median estimated daily intakes of acetamiprid, imidacloprid, and nitenpyram were 0.47, 1.27, and 0.02 µg/kg/d for females and 0.91, 0.66, and 0.08 µg/kg/d for males, respectively. The maximum daily intakes of all the NNIs were <1% of their chronic reference doses (cRfDs), except for imidacloprid and thiacloprid which recorded maximum daily intakes corresponding to 17.97 and 8.28% of cRfDs, respectively. To the best of our knowledge, the present study is the first biomonitoring report on neonicotinoid insecticides in Africa. Environ Toxicol Chem 2021;40:2306-2318. © 2021 SETAC.
• 二光子顕微鏡を用いた、ニコチン性アセチルコリン受容体アゴニストによる脳機能障害の検出

  平井 杏梨, 杉尾 翔太, Nimako Collins, 中山 翔太, 加藤 恵介, 高橋 圭介, 有薗 幸司, 平野 哲史, 星 信彦, 藤岡 一俊, 平 久美子, 石塚 真由美, 和氣 弘明, 池中 良徳

  The Journal of Toxicological Sciences 46 Suppl. S102 - S103 2021年07月
• 哺乳類における感情および認知行動に対するフィプロニルの効果【JST・京大機械翻訳】

  Suzuki Tomohiro, Hirai Anri, Khidkhan Kraisiri, Khidkhan Kraisiri, Nimako Collins, Ichise Takahiro, Takeda Kazuki, Mizukawa Hazuki, Nakayama Shouta M.M., Nomiyama Kei, Hoshi Nobuhiko, Maeda Mizuki, Hirano Tetsushi, Sasaoka Kazuyoshi, Sasaki Noboru, Takiguchi Mitsuyoshi, Ishizuka Mayumi, Ikenaka Yoshinori, Ikenaka Yoshinori, Ikenaka Yoshinori, Ikenaka Yoshinori

  Pesticide Biochemistry and Physiology 175 104847 - 104847 2021年06月 

  Fipronil is a phenylpyrazole insecticide that is widely used as a pesticide and a veterinary drug, although studies suggest that it could be toxic to mammals. The objectives of this study were to examine the pharmacokinetic profile of fipronil in mice, dogs, and cats, and to evaluate its effects on emotional and cognitive behaviors of dogs and cats using the data obtained from mice. The assessment of in vivo kinetics of fipronil was conducted in mice and dogs. We also performed behavioral tests (elevated plus-maze and Y-maze) and measured the levels of neurotransmitters in mice exposed to fipronil. In addition, the in vitro metabolism of fipronil were evaluated using liver microsomes of rats, mice, dogs, and cats. The results revealed that fipronil is distributed throughout the body (blood, brain, adipose tissue, and liver) of mice after dermal application. It was metabolized to fipronil sulfone primarily in the liver. The data on kinetics show that both fipronil and fipronil sulfone have a longer half-life in dogs and cats than in mice. The behavioral tests indicated that fipronil and fipronil sulfone could affect emotional and cognitive behaviors and alter the levels of neurotransmitters (dopamine in the striatum and serotonin in the hippocampus) in mice. Furthermore, we found that dogs and cats have a low ability to metabolize fipronil than mice and rats. However, further comprehensive studies are needed to determine whether fipronil affects the emotional and cognitive behaviors when administered to dogs and cats. To the best of our knowledge, this is the first study to examine the pharmacokinetic data and verify the effects of fipronil on emotional and cognitive behaviors of dogs and cats using the data obtained from mice.
• Genome-wide DNA methylation analysis of dogs with high lead exposure living near a lead mining area in Kabwe, Zambia.

  Jumpei Yamazaki, Haruya Toyomaki, Shouta M M Nakayama, John Yabe, Kaampwe Muzandu, Jaroslav Jelinek, Shoko Yokoyama, Yoshinori Ikenaka, Mitsuyoshi Takiguchi, Mayumi Ishizuka

  Environmental pollution (Barking, Essex : 1987) 286 117229 - 117229 2021年05月03日 

  Lead (Pb) is a heavy metal that has been proven to be toxic to both animals and humans. Genom-wide DNA methylation in domestic dogs exposed to high levels of Pb in Kabwe, Zambia was analyzed in this study. Using next-generation sequencing on samples from 20 domestic dogs (mean blood Pb concentration: 43.6 μg/dL and 7.2 μg/dL in the high and low exposure groups), a digital restriction enzyme analysis of methylation was performed to identify the genomic locations of differentially methylated CpG sites. A validation study on an additional 20 dogs followed (blood Pb concentration: 4.9-29.7 μg/dL). The cluster analysis resolved two broad clusters indicating high and low Pb exposure. The study identified 827 (1.2%) CpG sites with differences in methylation (101 CpG sites were hypermethylated in the low exposure group and 726 were hypermethylated in the high exposure group). The sites corresponded to 26 genes with differentially methylated CpG sites at their promoter regions, including the NGF gene. The methylation of four CpG sites was validated using bisulfite pyrosequencing. The results indicate that aberrant hypermethylation is prevalent in dogs exposed to Pb. The altered DNA methylation of the genes identified in this study contributes to a greater understanding of the epigenetic changes caused by Pb exposure and highlights novel biomarker discoveries across species.
• Delta-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genes polymorphisms in children residing in an abandoned lead-zinc mine area in Kabwe, Zambia

  Yared B. Yohannes, Shouta M. M. Nakayama, John Yabe, Haruya Toyomaki, Andrew Kataba, Hokuto Nakata, Kaampwe Muzandu, Yoshinori Ikenaka, Kennedy Choongo, Mayumi Ishizuka

  META GENE 27 2021年02月 

  Lead is a ubiquitous environmental pollutant that poses serious health problems to humans, especially to children. However, genetic variability in individuals varies their susceptibility to lead poisoning. One possible factor is genetic polymorphism. Thus, this study aimed to investigate the association between blood lead level (BLL), and polymorphisms in the delta-aminolevulinic acid dehydratase (ALAD) MspI (rs1800435) and vitamin D receptor (VDR) FokI (rs19735810), BsmI (rs15444410), ApaI (rs7975232) and TaqI (rs731236) genes in children exposed to lead. A total of 140 children (aged 2-10 years) were recruited in areas living closer to and far away from an abandoned lead-zinc mine in Kabwe, Zambia. Blood samples were collected from each child for BLLs and polymorphisms analysis.All children were homozygous for the ALAD 1 allele, indicating there might be bioavailable lead in the children's blood which can transfer to the soft tissues and the brain. The distribution of the VDR gene polymorphisms showed major alleles prevalence's of 81%, 80%, 68%, and 75% for FokI, BsmI, ApaI, and TaqI polymorphisms, respectively. The aa genotype of VDR ApaI showed significantly higher BLL compared to other genotypes of the VDRs polymorphism. The TaqI - TT genotype was associated with an increase of lead exposure risk in female children (OR = 2.06; 95% CI:1.04-4.06, p = 0.03). The haplotype analysis showed 10 haplotypes with a frequency above 1%, and the FbAt haplotype showed a protective role against lead toxicity. In conclusion, the children, especially female children, which exposed to lead mainly from the abandoned lead-zinc mine might be at a higher risk of developing lead poisoning. Further, larger scale sample sizes are needed to corroborate the role of ALAD and VDR genetic variants on the implications of lead toxicity in the general population, particularly in children.
• An Investigation of the Wild Rat Crown Incisor as an Indicator of Lead (Pb) Exposure Using Inductively Couple Plasma Mass Spectrometry (ICP-MS) and Laser Ablation ICP-MS.

  Andrew Kataba, Shouta M M Nakayama, Hokuto Nakata, Haruya Toyomaki, Yared B Yohannes, John Yabe, Kaampwe Muzandu, Golden Zyambo, Ayano Kubota, Takehisa Matsukawa, Kazuhito Yokoyama, Yoshinori Ikenaka, Mayumi Ishizuka

  International journal of environmental research and public health 18 2 2021年01月18日 

  Lead (Pb) is a metal toxicant of great public health concern. The present study investigated the applicability of the rat incisor in Pb exposure screening. The levels of lead in teeth (Pb-T) in the crown and root of incisors in laboratory Pb-exposed Sprague Dawley rats were quantified using inductively coupled plasma mass spectrometry (ICP-MS). The crown accumulated much Pb-T than the root of the Sprague Dawley rat incisor. The levels of lead in blood (Pb-B) were positively correlated with the Pb-T in the crown and root incisors of the Sprague Dawley rats. As an application of the Pb-T crown results in experimental rats, we subsequently analyzed the Pb-T in the crown incisors of Pb-exposed wild rats (Rattus rattus) sampled from residential sites within varying distances from an abandoned lead-zinc mine. The Pb-T accumulation in the crown of incisors of R. rattus rats decreased with increased distance away from the Pb-Zn mine. Furthermore, the Pb-T was strongly correlated (r = 0.85) with the Pb levels in the blood. Laser ablation ICP-MS Pb-T mappings revealed a homogenous distribution of Pb in the incisor with an increased intensity of Pb-T localized in the tip of the incisor crown bearing an enamel surface in both Sprague Dawley and R. rattus rats. These findings suggest that Pb-T in the crown incisor may be reflective of the rat's environmental habitat, thus a possible indicator of Pb exposure.
• 活動紹介：モンゴル生命科学大学との研究協力

  本平 航大, Dugar Delgermurun, 池中 良徳, 中山 翔太, Pelden Bolormaa, Gendenpil Lkhamjav, 石塚 真由美

  日本科学教育学会年会論文集 45 563 - 564 一般社団法人 日本科学教育学会 2021年 

  発表者は北海道大学のJICAを通じたプロジェクトの一環で２０１９年に青年海外協力隊（獣医師）としてモンゴル生命科学大学獣医学部に短期派遣され、約１か月の研究支援を実施した。モンゴル国では残留抗生物質の検査体制の拡大が望まれており、発表者の活動により、日本から大学研究レベルの検査手法の開発とその研究プロセスの伝達、共有が実現された。帰国後も、現在に至るまでFacebook Messengerなどのツールを利用し、追加の検査手法開発に向けた継続的な研究協力関係を構築した。結果として、国際会議における科学的成果発表など、今回の活動により一定の進展があったことを社会に報告できた。しかし、専門性の高い研究レベルの支援を遠隔で実施する過程で双方、難点を抱える場面があった。本発表により発表者が実施した研究支援を踏まえ、開発途上国に対する大学研究レベルの支援の一例紹介、またその課題を共有する。
• Neonicotinoid residues in commercial Japanese tea leaves produced by organic and conventional farming methods.

  Collins Nimako, Anri Hirai, Takahiro Ichise, Osei Akoto, Shouta M M Nakayama, Kumiko Taira, Kazutoshi Fujioka, Mayumi Ishizuka, Yoshinori Ikenaka

  Toxicology reports 8 1657 - 1664 2021年 

  The current study sought to assess the residual levels of neonicotinoid insecticides (NEO) in organic and conventional green tea leaves produced in Japan. A total of 103 tea leaves (thus, 42 organic and 61 conventional), were sampled from grocery stores in Japan. Concentrations of NEOs in the tea leaves were quantified using LC-MS/MS; and the data was used to estimate maximum daily intakes of NEOs within the Japanese population. Seven native NEO compounds and one NEO metabolite were detected in both organic and conventional tea leaves. Detection frequencies (%Dfs) of NEOs in the tea samples (n = 103) were found in the decreasing order; thiacloprid (84.47 %) > dinotefuran (74.76 %) > imidacloprid (69.90 %) ≈ clothianidin (69.90 %) > dm-acetamiprid (63.11 %) > thiamethoxam (58.25 %) > acetamiprid (4.85 %) > nitenpyram (1.94 %). About 94.20 % of the tea leaves contained two or more NEO compounds simultaneously. The %Dfs of NEOs were relatively lower in organic tea leaves, compared to the conventional tea leaves. Various percentile concentrations of NEOs were far lower in organic tea leaves, compared to the conventional tea leaves. The maximum daily intakes of NEOs through consumption of tea (MDIgt) were also lower for organic tea leaves, compared to the conventional tea samples.
• イミダクロプリドへの慢性低用量曝露はC57BL/6J雄マウスにおける高脂肪食媒介肝脂肪変性を高める

  NIMAKO Collins, IKENAKA Yoshinori, IKENAKA Yoshinori, OKAMATSU-OGURA Yuko, BARIUAN Jussiaea V., KOBAYASHI Atsushi, YAMAZAKI Ryo, TAIRA Kumiko, HOSHI Nobuhiko, HIRANO Tetsushi, NAKAYAMA Shouta M. M., ISHIZUKA Mayumi

  Journal of Veterinary Medical Science (Web) 83 3 487 - 500 2021年 

  Hepatic steatosis is known to precede a continuum of events that lead to hepatic metabolic dysfunction, inflammation and carcinogenesis. Recently, studies have linked xenobiotic exposures to hepatic steatogenesis and its associated metabolic disorders; however, the underlying mechanisms remain elusive. This study aimed to elucidate the mechanistic role of imidacloprid in the prevalence of high fat diet (HFD)-induced liver steatosis, using a C57BL/6J mice model. Mice (3 weeks old) were fed with HFD and treated with 0.6 mg/kg bw/day (one-tenth of the NOAEL) of imidacloprid through water or diet, for 24 weeks. In a controlled group, mice were fed with only HFD. At the end of the study, imidacloprid treatment significantly potentiated HFD-induced body weight gain in mice. Also, imidacloprid increased the liver weights of mice, with complimentary reductions in mesenteric and gonadal white adipose tissue weights. Histopathological analysis of liver revealed a drastic steatosis in imidacloprid treated mice. Following a real-time qPCR analysis, imidacloprid upregulated transcriptions of hepatic fatty acid biosynthesis-related transcription factors and genes. Imidacloprid also induced hepatic expression of the gene encoding pregnane X receptor; but had no significant effect on hepatic expressions of liver X receptor and aryl hydrocarbon receptor. The imidacloprid treatment further enhanced serum alanine aminotransferase levels but downregulated hepatic antioxidant mRNA expressions. Ultimately, this study suggested an imidacloprid-potentiation effects on prevalence of HFD-induced liver steatosis via transcriptional modulations of the hepatic FA biosynthesis pathway.
• 雄性マウスにおけるネオニコチノイド殺虫剤クロチアニジンの行動効果の感受性における加齢関連変化【JST・京大機械翻訳】

  Hirano Tetsushi, Miyata Yuka, Kubo Shizuka, Ohno Shuji, Onaru Kanoko, Maeda Mizuki, Kitauchi Sayaka, Nishi Misaki, Tabuchi Yoshiaki, Ikenaka Yoshinori, Ikenaka Yoshinori, Ichise Takahiro, Nakayama Shouta M.M., Ishizuka Mayumi, Arizono Koji, Takahashi Keisuke, Kato Keisuke, Mantani Youhei, Yokoyama Toshifumi, Hoshi Nobuhiko

  Toxicology Letters 342 95 - 103 2021年 

  Neonicotinoids, which act as agonists of the nicotinic acetylcholine receptors of insects, are widely used pesticides worldwide. Although epidemiological studies revealed that the detection amounts of neonicotinoids in urine are higher in the elderly population than other age-groups, there is no available information regarding the risks of neonicotinoids to older mammals. This study was aimed to investigate aging-related differences in the behavioral effects of the neonicotinoid pesticide clothianidin (CLO). We acutely administered a sub-NOAEL level (5 mg/kg) of CLO to adult (12-week-old) and aging (90-week-old) mice and conducted four behavioral tests focusing on the emotional behavior. In addition, we measured the concentrations of CLO and its metabolites in blood, brain and urine. There were age-related changes in most parameters in all behavioral tests, and CLO significantly decreased the locomotor activity in the open field test and elevated plus-maze test in the aging group, but not in the adult group. The concentrations of most CLO and its metabolites were significantly higher in the blood and brain and were slightly lower in the urine in the aging group compared to the adult group. These findings should contribute to our understanding of age-related differences in the adverse effects of neonicotinoids in mammals.
• 抗凝固殺鼠剤に対するカメの感受性:小笠原諸島におけるアオウミガメ(Chelonia mydas)のリスク評価とカメ種間のワルファリン感受性の比較【JST・京大機械翻訳】

  Yamamura Yoshiya, Takeda Kazuki, Kawai Yusuke K., Ikenaka Yoshinori, Ikenaka Yoshinori, Kitayama Chiyo, Kondo Satomi, Kezuka Chiho, Taniguchi Mari, Ishizuka Mayumi, Nakayama Shouta M.M.

  Aquatic Toxicology 233 105792 - 105792 2021年 

  Although anticoagulant rodenticides (ARs) are effectively used for the control of invasive rodents, nontarget species are also frequently exposed to ARs and secondary poisonings occur widely. However, little data is available on the effects of ARs, especially on marine organisms. To evaluate the effects of ARs on marine wildlife, we chose green sea turtles (Chelonia mydas), which are one of the most common marine organisms around the Ogasawara islands, as our primary study species. The sensitivity of these turtles to ARs was assessed using both in vivo and in vitro approaches. We administered 4 mg/kg of warfarin sodium either orally or intravenously to juvenile green sea turtles. The turtles exhibited slow pharmacokinetics, and prolongation of prothrombin time (PT) was observed only with intravenous warfarin administration. We also conducted an in vitro investigation using liver microsomes from green sea turtles, and two other turtle species (softshell turtle and red-eared slider) and rats. The cytochrome P450 metabolic activity in the liver of green sea turtles was lower than in rats. Additionally, vitamin K epoxide reductase (VKOR), which is the target enzyme of ARs, was inhibited by warfarin in the turtles at lower concentration levels than in rats. These data indicate that turtles may be more sensitive to ARs than rats. We expect that these findings will be helpful for sea turtle conservation following accidental AR-broadcast incidents.
• ICP-MS分析と比較した広範囲の血中鉛レベルの試験のための鉛Care II分析の評価【JST・京大機械翻訳】

  Nakata Hokuto, Nakayama Shouta M.M., Yabe John, Muzandu Kaampwe, Toyomaki Haruya, Yohannes Yared Beyene, Yohannes Yared Beyene, Kataba Andrew, Kataba Andrew, Zyambo Golden, Ikenaka Yoshinori, Ikenaka Yoshinori, Choongo Kennedy, Choongo Kennedy, Ishizuka Mayumi

  Chemosphere 271 129832 - 129832 2021年 

  The LeadCare® testing system, which utilizes anodic stripping voltammetry (ASV) methodology, has been widely used worldwide for cost-effective blood lead level (BLL) screening. However, some concerns have recently been issued regarding inaccurate results obtained using LeadCare®. Hence, we aimed to evaluate the accuracy of BLL measured by LeadCare® II (BLLLC) by comparison with ICP-MS (BLLIM) by the Passing-Bablok regression, Deming regression, and Bland-Altman analyses by using 994 venous blood samples. BLLLC ranged from 3.3 to 162.3 μg/dL, while BLLIM ranged from 0.8 to 154.8 μg/dL. Although BLLLC and BLLIM exhibited a strong and positive correlation, BLLLC values were generally greater than BLLIM values, indicative of the overestimation of the LeadCare® analysis. A large positive bias of 19.15 ± 8.26 μg/dL and 29.25 ± 14.04 μg/dL for BLLLC compared with BLLIM were recorded in the BLLLC range of 45.0-64.9 μg/dL and for ≥65.0 μg/dL, respectively. In contrast, a bias of ≤0.3 μg/dL was observed at a BLLLC of less than 10.0 μg/dL. Blood copper, cadmium, and iron levels did not exhibit an effect on the bias of BLLLC, indicative of the minimal potential interferences of the metals; these interferences are a cause for concern with the ASV method. In conclusion, LeadCare® analysis is thought to be a good tool for screening purposes at a lower BLL around the reference level of 5 μg/dL in the initial stage; however, conversion or retesting using a laboratory analyzer is recommended at a higher BLL for appropriate clinical evaluation and research.
• VKORC1 ER-管腔ループ変異(Leu76Pro)は黒ラット(クマネズミ)におけるワルファリンへの有意な耐性をもたらす【JST・京大機械翻訳】

  Takeda Kazuki, Ikenaka Yoshinori, Ikenaka Yoshinori, Fourches Denis, Tanaka Kazuyuki D., Nakayama Shouta M.M., Triki Dhoha, Li Xinhao, Igarashi Manabu, Igarashi Manabu, Tanikawa Tsutomu, Ishizuka Mayumi

  Pesticide Biochemistry and Physiology 173 104774 - 104774 2021年 

  Well-known 4-hydroxycoumarin derivatives, such as warfarin, act as inhibitors of the vitamin K epoxide reductase (VKOR) and are used as anticoagulants. Mutations of the VKOR enzyme can lead to resistance to those compounds. This has been a problem in using them as medicine or rodenticide. Most of these mutations lie in the vicinity of potential warfarin-binding sites within the ER-luminal loop structure (Lys30, Phe55) and the transmembrane helix (Tyr138). However, a VKOR mutation found in Tokyo in warfarin-resistant rats does not follow that pattern (Leu76Pro), and its effect on VKOR function and structure remains unclear. We conducted both in vitro kinetic analyses and in silico docking studies to characterize the VKOR mutant. On the one hand, resistant rats (R-rats) showed a 37.5-fold increased IC50 value to warfarin when compared to susceptible rats (S-rats); on the other hand, R-rats showed a 16.5-fold lower basal VKOR activity (Vmax/Km). Docking calculations exhibited that the mutated VKOR of R-rats has a decreased affinity for warfarin. Molecular dynamics simulations further revealed that VKOR-associated warfarin was more exposed to solvents in R-rats and key interactions between Lys30, Phe55, and warfarin were less favored. This study concludes that a single mutation of VKOR at position 76 leads to a significant resistance to warfarin by modifying the types and numbers of intermolecular interactions between the two.
• LA-ICP-MSによる鳥類臓器中の鉛分布の分析:実験的に鉛曝露したアヒルとキットの研究【JST・京大機械翻訳】

  Torimoto Ryouta, Ishii Chihiro, Sato Hiroshi, Saito Keisuke, Watanabe Yukiko, Ogasawara Kohei, Kubota Ayano, Matsukawa Takehisa, Matsukawa Takehisa, Yokoyama Kazuhito, Yokoyama Kazuhito, Kobayashi Atsushi, Kimura Takashi, Nakayama Shouta M.M., Ikenaka Yoshinori, Ikenaka Yoshinori, Ishizuka Mayumi

  Environmental Pollution 283 117086 - 117086 2021年 

  Lead poisoning of wild birds by ingestion of lead ammunition occurs worldwide. Histopathological changes in organs of lead-intoxicated birds are widely known, and lead concentration of each organ is measurable using mass spectrometry. However, detailed lead localization at the suborgan level has remained elusive in lead-exposed birds. Here we investigated the detailed lead localization in organs of experimentally lead-exposed ducks and kites by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). In both the ducks and kites, lead accumulated diffusely in the liver, renal cortex, and brain. Lead accumulation was restricted to the red pulp in the spleen. With regard to species differences in lead distribution patterns, it is noteworthy that intensive lead accumulation was observed in the arterial walls only in the kites. In addition, the distribution of copper in the brain was altered in the lead-exposed ducks. Thus, the present study shows suborgan lead distribution in lead-exposed birds and its differences between avian species for the first time. These findings will provide fundamental information to understand the cellular processes of lead poisoning and the mechanisms of species differences in susceptibility to lead exposure.
• 母親の健康関連QOLに及ぼす子供の血中鉛濃度上昇の影響【JST・京大機械翻訳】

  Nakata Hokuto, Tohyama Harukazu, Fujita Wakako, Fujita Wakako, Nakayama Shouta M.M., Ishizuka Mayumi, Yabe John, Munyinda Nosiku S., Sakala Doreen, Choongo Kennedy, Choongo Kennedy, Yamasaki Shojiro, Nagai Natsumi, Yoshida Takahiko, Saito Takeshi

  Chemosphere 279 130490 - 130490 2021年 

  Kabwe is a mining town in Zambia that has been ranked among "the ten most polluted places in the world" with previous findings of serious lead (Pb) pollution. In this study, we aim to examine the impact of childhood Pb poisoning on the health-related quality of life (HRQoL) of mothers in Kabwe. The HRQoL was assessed using the Short-Form 36 survey for 404 mothers coming from residences in 40 randomly selected standard enumeration areas (SEAs). Blood lead levels (BLLs) of the household members including the mothers themselves were measured. We found a significant positive correlation between the BLLs of the mothers and their children (R = 0.6385, p < 0.0001), while the BLLs of preschool-aged and school-aged children were significantly higher than those of their mothers and fathers. Using the data sets containing the BLLs of the household members, the age of the mothers, the household income, and the household SEA, we performed stepwise multiple linear regression analyses. The results showed significant negative associations between the representative BLL of household children and the BLL of preschool-aged children with the vitality and mental health scores of their mothers. Additionally, the BLL of school-aged children was only significantly associated with the mental health score of their mothers. By contrast, there was a significant negative association between the BLLs of the mothers with the social role functioning score. This suggests that elevated BLLs in children have a negative impact on the mental health conditions of their mothers regardless of the mothers' BLL.
• 南アフリカのマラリアリスク地域内の2つの保全地域からの両生類におけるDDTと他の有機塩素系農薬の生体内蓄積【JST・京大機械翻訳】

  Wolmarans Nico J., Wolmarans Nico J., Bervoets Lieven, Gerber Ruan, Yohannes Yared Beyene, Nakayama Shouta MM., Ikenaka Yoshinori, Ikenaka Yoshinori, Ishizuka Mayumi, Meire Patrick, Smit Nico J., Wepener Victor, Wepener Victor

  Chemosphere 274 129956 - 129956 2021年 

  The threat to wildlife from chemical exposure exists regardless of the presence of conservation boundaries. An issue exacerbated by the use of environmentally persistent insecticides for vector control and long-range transport of legacy persistent organic pollutants. In this comparative study between two important conservation regions in South Africa, Kruger National Park (KNP) and Ndumo Game Reserve (NGR), we assessed organochlorine pesticide (OCP) accumulation in several anuran species collected from within the conservation regions. The two conservation regions differ in size and subsequent proximity of collection sites to OCP input sources. Detectable concentrations of OCPs were present in ∼ half the frogs analysed from KNP and ∼all frogs from NGR and total OCP loads were similar between regions, where measured in the same species. The OCP profiles in KNP frogs were representative of legacy pesticides likely introduced via long-range transport, whereas NGR profiles showed influence of current use of DDT consistent with close proximity to sources. This indicates amphibians can accumulate OCPs within conservation regions and that the exposure of non-target organisms inside conservation regions to current use pesticides has a strong association with proximity to sources. These results serve to inform conservation management decision making with regard to the non-target organism effects of chemical interventions such as vector control pesticide use in and around conservation regions.
• ネコ,イヌ,ラットおよびヒトにおけるネオニコチノイドのチトクロームP450媒介代謝における種間差【JST・京大機械翻訳】

  Khidkhan Kraisiri, Ikenaka Yoshinori, Ikenaka Yoshinori, Ichise Takahiro, Nakayama Shouta M.M., Mizukawa Hazuki, Mizukawa Hazuki, Nomiyama Kei, Iwata Hisato, Arizono Koji, Takahashi Keisuke, Kato Keisuke, Ishizuka Mayumi

  Comparative Biochemistry and Physiology. C. Toxicology & Pharmacology 239 108898 - 108898 2021年 

  Neonicotinoid insecticides are used for agricultural and non-agricultural purposes worldwide. Pets are directly exposed to neonicotinoids in veterinary products and through environmental contamination. Cytochrome P450 (CYP) is among the most significant xenobiotic metabolizing enzymes that oxidizes several chemicals, including neonicotinoids. However, CYP activities and metabolite compositions of neonicotinoid metabolites are unknown in most domesticated pet species. Our objectives were to reveal the differences in metabolites of neonicotinoids (imidacloprid, clothianidin, and acetamiprid) and CYP activities among common pet species (cats and dogs), humans, and rats. The results indicated that the CYP-mediated neonicotinoid metabolism was different depending on species and each neonicotinoid. Among these four species, the kinetics of imidacloprid metabolism indicated that rats have the highest rate of oxidation of imidacloprid to 4OH-imidacloprid, while the greatest enzyme kinetics of imidacloprid metabolism to 5OH-imidacloprid were found in rats and humans. Clothianidin was rapidly metabolized to 1-methyl-3-nitroguanidine and dm-clothianidin in rats, but cats and humans showed the lowest formation of dm-clothianidin. CYP activities in metabolism of acetamiprid to dm-acetamiprid and N-acetyl-acetamiprid were determined to be significantly higher in humans compared to other species. However, further studies should be targeted at identifying the differences in hepatic metabolism of neonicotinoids in these species using recombinant CYP enzymes.
• Clinical biochemical parameters associated with the exposure to multiple environmental metals in residents from Kabwe, Zambia.

  Hokuto Nakata, Shouta M M Nakayama, John Yabe, Kaampwe Muzandu, Haruya Toyomaki, Yared Beyene Yohannes, Andrew Kataba, Golden Zyambo, Yoshinori Ikenaka, Kennedy Choongo, Mayumi Ishizuka

  Chemosphere 262 127788 - 127788 2021年01月 

  Lead (Pb) interferes with various bodily functions. Although high blood Pb (Pb-B) levels in residents from Kabwe, Zambia have been reported, the accumulation pattern of other metals remains unknown. The study was designed to determine the Pb-B, blood cadmium (Cd-B), and zinc (Zn-B) values of 504 representative samples from Kabwe, as well as the potential associated adverse health effects. The Pb-B level ranged from 0.79 to 154.75 μg/dL and generally increased in areas near the mine. A significant elevation of Cd-B was observed in two areas (0.37 ± 0.26 and 0.32 ± 0.30 μg/L) where the two highest mean Pb-B levels were recorded. By contrast, the Zn-B values did not differ greatly with respect to area. Some blood biochemical parameters relating to hepatic and renal functions were out of the normal range in approximately 20-50% of studied adult participants. The δ-aminolevulinic acid dehydratase (δ-ALAD) activity was significantly inhibited in the two areas contaminated by Pb and Cd. A significant negative relationship was observed between metal levels and clinical parameters, e.g., between Pb-B and δ-ALAD for all the age categories and between Cd-B and the estimated glomerular filtration rate for all the age categories except 0-4 years. The elevated Cd-B in areas near the mine relative to the other areas suggested the potential adverse health effects of Cd and/or the interaction of Pb and Cd. A significant association of metal levels with clinical parameters also indicated the effects of metal exposure on hematopoietic, hepatic, and renal systems.
• Biosorption of Pb (II) and Zn (II) from aqueous solution by Oceanobacillus profundus isolated from an abandoned mine.

  Wilson Mwandira, Kazunori Nakashima, Satoru Kawasaki, Allison Arabelo, Kawawa Banda, Imasiku Nyambe, Meki Chirwa, Mayumi Ito, Tsutomu Sato, Toshifumi Igarashi, Hokuto Nakata, Shouta Nakayama, Mayumi Ishizuka

  Scientific reports 10 1 21189 - 21189 2020年12月03日 

  The present study investigated biosorption of Pb (II) and Zn (II) using a heavy metal tolerant bacterium Oceanobacillus profundus KBZ 3-2 isolated from a contaminated site. The effects of process parameters such as effect on bacterial growth, pH and initial lead ion concentration were studied. The results showed that the maximum removal percentage for Pb (II) was 97% at an initial concentration of 50 mg/L whereas maximum removal percentage for Zn (II) was at 54% at an initial concentration of 2 mg/L obtained at pH 6 and 30 °C. The isolated bacteria were found to sequester both Pb (II) and Zn (II) in the extracellular polymeric substance (EPS). The EPS facilitates ion exchange and metal chelation-complexation by virtue of the existence of ionizable functional groups such as carboxyl, sulfate, and phosphate present in the protein and polysaccharides. Therefore, the use of indigenous bacteria in the remediation of contaminated water is an eco-friendly way of solving anthropogenic contamination.
• Land Use in Habitats Affects Metal Concentrations in Wild Lizards Around a Former Lead Mining Site.

  Rio Doya, Shouta M M Nakayama, Hokuto Nakata, Haruya Toyomaki, John Yabe, Kaampwe Muzandu, Yared B Yohannes, Andrew Kataba, Golden Zyambo, Takahiro Ogawa, Yoshitaka Uchida, Yoshinori Ikenaka, Mayumi Ishizuka

  Environmental science & technology 54 22 14474 - 14481 2020年11月17日 [査読有り][通常論文]
   

  We investigated the potential effects of different land use and other environmental factors on animals living in a contaminated environment. The study site in Kabwe, Zambia, is currently undergoing urban expansion, while lead contamination from former mining activities is still prevalent. We focused on a habitat generalist lizards (Trachylepis wahlbergii). The livers, lungs, blood, and stomach contents of 224 lizards were analyzed for their lead, zinc, cadmium, copper, nickel, and arsenic concentrations. Habitat types were categorized based on vegetation data obtained from satellite images. Multiple regression analysis revealed that land use categories of habitats and three other factors significantly affected lead concentrations in the lizards. Further investigation suggested that the lead concentrations in lizards living in bare fields were higher than expected based on the distance from the contaminant source, while those in lizards living in green fields were lower than expected. In addition, the lead concentration of lungs was higher than that of the liver in 19% of the lizards, implying direct exposure to lead via dust inhalation besides digestive exposure. Since vegetation reduces the production of dust from surface soil, it is plausible that dust from the mine is one of the contamination sources and that vegetation can reduce exposure to this.
• Acute exposure to environmentally relevant lead levels induces oxidative stress and neurobehavioral alterations in larval zebrafish (Danio rerio).

  Andrew Kataba, Tarryn L Botha, Shouta M M Nakayama, Yared B Yohannes, Yoshinori Ikenaka, Victor Wepener, Mayumi Ishizuka

  Aquatic toxicology (Amsterdam, Netherlands) 227 105607 - 105607 2020年10月 

  The ubiquitous contamination of environmental lead (Pb) remains a worldwide threat. Improper Pb mine waste disposal from an abandoned lead-zinc mine has recently unearthed widespread Pb poisoning in children in Kabwe Zambia. Although the adverse effects of Pb on human health have begun to receive attention, the ecotoxicological effects on aquatic vertebrates still need further investigation. In addition, there is paucity in the knowledge on the behavioural and molecular subcellular responses in larval zebrafish exposed to Pb within the range of environmental relevant concentration (average 3 μg/L with maximum of 94 μg/L) on aquatic organisms such as zebrafish. The adverse effects of environmentally relevant levels of Pb on larval zebrafish was evaluated by measuring swimming behaviour under alternating dark and light conditions. Larval zebrafish acutely exposed to environmentally relevant Pb exhibited neuro-behavioural alteration including enhanced hyperactivity under light conditions evidenced by increased distanced covered and speed compared to the control. The alteration of entire behavioral profiles was further associated with the disturbed expression patterns of mRNA level of key genes associated with antioxidant (HO-1, Ucp-2 and CoxI), proapoptotic gene (TP53), and antiapoptotic gene (Bcl-2). To our knowledge, this is the first report on the effects of environmentally relevant Pb levels from Kabwe, Zambia and their adverse neurobehavioural effects and subcellular molecular oxidative responses in larval zebrafish acutely exposed within a 30 min period. The current results would be beneficial in our understanding of the effects of low Pb levels acutely discharged into an aquatic environment and the life of aquatic organisms.
• Assessing the population-wide exposure to lead pollution in Kabwe, Zambia: an econometric estimation based on survey data.

  Daichi Yamada, Masato Hiwatari, Peter Hangoma, Daiju Narita, Chrispin Mphuka, Bona Chitah, John Yabe, Shouta M M Nakayama, Hokuto Nakata, Kennedy Choongo, Mayumi Ishizuka

  Scientific reports 10 1 15092 - 15092 2020年09月15日 

  This study quantitatively assessed the population-wide lead poisoning conditions in Kabwe, Zambia, a town with severe lead pollution. While existing data have reported concerning blood lead levels (BLLs) of residents in pollution hotspots, the data representing the entire population are lacking. Further, selection bias is a concern. Given the lack of compulsory testing schemes, BLLs have been observed from voluntary participants in blood sampling surveys, but such data can represent higher or lower BLLs than the population average because of factors simultaneously affecting participation and BLLs. To illustrate the lead poisoning conditions of the population, we expanded the focus of our surveys and then econometrically estimated the BLLs of individuals representing the population, including those not participating in blood sampling, using background geographic, demographic, and socioeconomic information. The estimated population mean BLL was 11.9 μg/dL (11.6-12.1, 95% CI), lower than existing data because of our wide focus and correction of selection bias. However, the scale of lead poisoning remained immense and 74.9% of residents had BLLs greater than 5 μg/dL, the standard reference level for lead poisoning. Our estimates provide a deeper understanding of the problem and a foundation for policy intervention designs.
• Immobilization of Lead and Zinc Leached from Mining Residual Materials in Kabwe, Zambia: Possibility of Chemical Immobilization by Dolomite, Calcined Dolomite, and Magnesium Oxide

  Pawit Tangviroon, Kenta Noto, Toshifumi Igarashi, Takeshi Kawashima, Mayumi Ito, Tsutomu Sato, Walubita Mufalo, Meki Chirwa, Imasiku Nyambe, Hokuto Nakata, Shouta Nakayama, Mayumi Ishizuka

  MINERALS 10 9 2020年09月 

  Massive amount of highly contaminated mining residual materials (MRM) has been left unattended and has leached heavy metals, particularly lead (Pb) and zinc (Zn) to the surrounding environments. Thus, the performance of three immobilizers, raw dolomite (RD), calcined dolomite (CD), and magnesium oxide (MO), was evaluated using batch experiments to determine their ability to immobilize Pb and Zn, leached from MRM. The addition of immobilizers increased the leachate pH and decreased the amounts of dissolved Pb and Zn to different extents. The performance of immobilizers to immobilize Pb and Zn followed the following trend: MO > CD > RD. pH played an important role in immobilizing Pb and Zn. Dolomite in RD could slightly raise the pH of the MRM leachate. Therefore, the addition of RD immobilized Pb and Zn via adsorption and co-precipitation, and up to 10% of RD addition did not reduce the concentrations of Pb and Zn to be lower than the effluent standards in Zambia. In contrast, the presence of magnesia in CD and MO significantly contributed to the rise of leachate pH to the value where it was sufficient to precipitate hydroxides of Pb and Zn and decrease their leaching concentrations below the regulated values. Even though MO outperformed CD, by considering the local availability of RD to produce CD, CD could be a potential immobilizer to be implemented in Zambia.
• Blood lead levels and aberrant DNA methylation of the ALAD and p16 gene promoters in children exposed to environmental-lead.

  Yared B Yohannes, Shouta Mm Nakayama, John Yabe, Hokuto Nakata, Haruya Toyomaki, Andrew Kataba, Kaampwe Muzandu, Yoshinori Ikenaka, Kennedy Choongo, Mayumi Ishizuka

  Environmental research 188 109759 - 109759 2020年09月 [査読有り][通常論文]
   

  BACKGROUND: Lead (Pb) is a well-known toxic heavy metal which can have serious public health hazards. As of today, there is no safe threshold for Pb exposure, especially for children. Lead exposure has been associated with adverse health outcomes involving epigenetic mechanisms, such as aberrant DNA methylation. The objective of the present study was to elucidate the associations between blood lead levels (BLLs) and gene-specific promoter DNA methylation status in environmental Pb-exposed children from Kabwe, Zambia. METHODS: A cross-sectional study was conducted using 2 to 10-year-old children from high Pb exposed area (N = 102) and low Pb exposed area (N = 38). We measured BLLs using a LeadCare II analyzer and investigated the methylation status of the ALAD and p16 gene promoters by methylation-specific PCR. RESULTS: The mean BLLs were 23.7 μg/dL and 7.9 μg/dL in high Pb exposed and low Pb exposed children, respectively. Pb exposure was correlated with increased methylation of the ALAD and p16 genes. The promoter methylation rates of ALAD and p16 in high Pb exposed children were 84.3% and 67.7%, and 42.1% and 44.7% in low Pb exposed children, respectively. Significantly increased methylation was found in both genes in high Pb exposed children compared with low Pb exposed children (p < 0.05). Children with methylated ALAD and p16 genes showed an increased risk of Pb poisoning (odd ratio >1) compared to the unmethylated status. CONCLUSIONS: This study for the first time tries to correlate promoter methylation status of the ALAD and p16 genes in environmental Pb-exposed children from Kabwe, Zambia as a representative. The result suggests that Pb exposure increases aberrations in ALAD and p16 gene methylation, which may be involved in the mechanism of Pb toxicity.
• Relationship between blood test values and blood lead (Pb) levels in Black-headed gull (Chroicocephalus ridibundus: Laridae).

  Nana Ushine, Shouta M M Nakayama, Mayumi Ishizuka, Tatsuo Sato, Yoshihiro Kurahashi, Emu Wakayama, Natsuko Sugiura, Shin-Ichi Hayama

  The Journal of veterinary medical science 82 8 1124 - 1129 2020年08月19日 [査読有り][通常論文]
   

  Few studies have evaluated immunosuppression due to lead accumulation below the overt toxicity threshold. If low levels of lead accumulation cause immunosuppression in birds, those birds could become more susceptible to pathogens. We aimed to determine if low levels of lead accumulation lead to immunosuppression in Black-headed gulls (Chroicocephalus ridibundus). Gulls were captured in Tokyo-bay and Mikawa-bay from January to April 2019. Their blood samples were analyzed for eight items. The data were analyzed to evaluate the correlation between lead concentrations and the variables from each bay. Lead was positively correlated with the percentage of heterophils and heterophil and lymphocyte ratio and negatively with lymphocytes. Thus, low lead accumulation levels may induce changes in percentage of the heterophils and lymphocyte.
• Current situation regarding lead exposure in birds in Japan (2015-2018); lead exposure is still occurring.

  Chihiro Ishii, Yoshinori Ikenaka, Shouta M M Nakayama, Takeshi Kuritani, Mitsuhiro Nakagawa, Keisuke Saito, Yukiko Watanabe, Kohei Ogasawara, Manabu Onuma, Atsushi Haga, Mayumi Ishizuka

  The Journal of veterinary medical science 82 8 1118 - 1123 2020年08月19日 [査読有り][通常論文]
   

  Birds of a number of species have died as a result of lead (Pb) poisoning, including many Steller's sea eagles (Haliaeetus pelagicus) and white-tailed sea eagles (Haliaeetus albicilla) in Hokkaido, the northernmost island of Japan. To address this issue, the use of any type of Pb ammunition for hunting of large animals was prohibited in Hokkaido in 2004. However, Pb poisoning is still being reported in this area, and there are few regulations regarding the use of Pb ammunition in other parts of Japan, where it has been reported that eagles and water birds have been exposed to Pb. This study was performed to accurately determine the current level of Pb exposure of birds found dead in the field or dead in the wild bird centers in Japan (June 2015-May 2018) and to identify the sources of Pb. Pb exposure was found to still be occurring in raptors and water birds in various parts of Japan. Twenty-six point five % and 5.9% of the recorded deaths of Steller's sea eagles and white-tailed sea eagles, respectively, were found to have been poisoned by Pb. In addition, Pb isotope ratio analysis showed that both Pb rifle bullets and Pb shot pellets cause Pb exposure in birds, and these endangered eagles are also exposed to Pb in Hokkaido due to the illegal use of Pb ammunition. Changing to Pb-free ammunition, such as copper (Cu) rifle bullets, steel shot pellets, or bismuth shot pellets, will be essential for the conservation of avian species in Japan.
• Detoxification of lead-bearing zinc plant leach residues from Kabwe, Zambia by coupled extraction-cementation method

  Marthias Silwamba, Mayumi Ito, Naoki Hiroyoshi, Carlito Baltazar Tabelin, Tomoki Fukushima, Ilhwan Park, Sanghee Jeon, Toshifumi Igarashi, Tsutomu Sato, Imasiku Nyambe, Meki Chirwa, Kawawa Banda, Hokuto Nakata, Shouta Nakayama, Mayumi Ishizuka

  Journal of Environmental Chemical Engineering 8 4 104197 - 104197 2020年08月 [査読有り][通常論文]
  
• Trophic transfer of pollutants within two intertidal rocky shore ecosystems in different biogeographic regions of South Africa.

  Anja Erasmus, Yoshinori Ikenaka, Shouta M M Nakayama, Mayumi Ishizuka, Nico J Smit, Victor Wepener

  Marine pollution bulletin 157 111309 - 111309 2020年08月 [査読有り][通常論文]
   

  Tsitsikamma and Sheffield Beach are two relatively pristine sites along the South African east coast representing warm temperate and subtropical biogeographic rocky shore intertidal ecosystems, respectively. Stable isotopes (δ15N and δ13C), metals and organochlorine pesticides (OCPs) were measured in 38 intertidal components to study biomagnification or biodilution of metals and OCPs in these marine food webs. Comparison of the four species common to both sites revealed that the highest Al, Fe and OCP concentrations were measured in intertidal organisms from Sheffield Beach and was attributed to diffuse input into the nearshore marine environment sources via estuaries and groundwater. All other metals were higher in intertidal organisms from Tsitsikamma and were attributed to the metal-rich phytoplankton blooms during upwelling events. There was no correlation between metal and OCP accumulation and dietary source (δ13C) or trophic level (δ15N). The application of trophic magnification factors (TMFs) using a relatively short benthic food chain indicated biomagnification for As, Cd, Cu, Se and Zn and biodilution of OCPs at both sites. Since these food chains represent only a small portion of the intertidal ecosystems we found limited evidence of biomagnification or biodilution of metals and OCPs across species. This was attributed to different dietary sources in the same food web and similar trophic levels being occupied by the same species in different food chains. We found that food web composition rather than temperature-based biogeographical distribution influenced trophic transfer of metals and OCPs.
• Comparison of two reducing agents dithiothreitol and tris(3-hydroxypropyl)phosphine for in vitro kinetic assay of vitamin K epoxide reductase.

  Kazuki Takeda, Ayuko Morita, Yoshinori Ikenaka, Shouta M M Nakayama, Mayumi Ishizuka

  Veterinary and animal science 9 100095 - 100095 2020年06月 [査読有り][通常論文]
   

  Vitamin K epoxide reductase (VKOR) is a target enzyme for anticoagulants, such as warfarin, that are used as medicines or rodenticides. Assessing VKOR activity is required to ensure the proper usage of these drugs. Dithiothreitol (DTT) is a typical disulfide reductant that is used as a substrate for in vitro VKOR assays. However, DTT is considered problematic because of its side effects. Tris(3-hydroxypropyl)phosphine (THP) has been found to be a reliable alternative to DTT, as shown by kinetic analyses of the VKOR with them. THP showed significantly lower V max and Km values than those of DTT; however, there was no significant difference in their V max/Km and IC50 for warfarin.
• Factors associated with lead (Pb) exposure on dogs around a Pb mining area, Kabwe, Zambia.

  Haruya Toyomaki, John Yabe, Shouta M M Nakayama, Yared B Yohannes, Kaampwe Muzandu, Allan Liazambi, Yoshinori Ikenaka, Takeshi Kuritani, Mitsuhiro Nakagawa, Mayumi Ishizuka

  Chemosphere 247 125884 - 125884 2020年05月 [査読有り][通常論文]
   

  Lead (Pb)-poisoning is a serious public health concern and dogs have been useful as a sentinel-animal for Pb exposure of humans. In the present study, the blood Pb concentrations (BLC), isotope ratios (208 Pb/206 Pb and 207 Pb/206 Pb), and biochemistry of 120 domestically owned dogs living around a Pb mining area, in Kabwe, Zambia were analyzed to determine factors associated with Pb exposure. The overall mean value of Pb in dog blood in the present study was 271.6 μg/L. The BLC in the dogs from sites near the mine were significantly higher than those in the dogs from a site 4 km from the mine (352.9 ± 205.1 μg/L versus 28.0 ± 13.9 μg/L). BLC significantly decreased with both increasing age of the dogs and distance from the mine. The Pb isotope ratios in the dog that resided near the mine showed values similar to those reported at the galena mine in Kabwe, which is considered to be the source of Pb exposure. In contrast to the high metal exposure that was determined in these dogs, the mean values of most analyzed parameters in the blood biochemical analysis were surprisingly within or close to the standard reference values. Moreover, none of the dogs showed overt signs of Pb-poisoning or other clinical symptoms. The results of analysis of Pb exposure of the dogs obtained in the present study, which are similar to the previously reported results in human in this location, suggest that dogs could be useful as a sentinel animal for Pb exposure of humans in Kabwe.
• Recovery of Lead and Zinc from Zinc Plant Leach Residues by Concurrent Dissolution-Cementation Using Zero-Valent Aluminum in Chloride Medium

  Marthias Silwamba, Mayumi Ito, Naoki Hiroyoshi, Carlito Baltazar Tabelin, Ryota Hashizume, Tomoki Fukushima, Ilhwan Park, Sanghee Jeon, Toshifumi Igarashi, Tsutomu Sato, Meki Chirwa, Kawawa Banda, Imasiku Nyambe, Hokuto Nakata, Shouta Nakayama, Mayumi Ishizuka

  Metals 10 4 531 - 531 2020年04月20日 [査読有り][通常論文]
   

  Zinc plant leach residues (ZPLRs) contain significant amounts of metal compounds of lead (Pb), zinc (Zn), iron (Fe), etc., hence, they are considered as a secondary source of metals. On the other hand, ZPLRs are regarded as hazardous materials because they contain heavy metals that pollute the environment. Resources and environmental concerns of ZPLRs were addressed in this study by removing/recovering Pb and Zn using a concurrent dissolution and cementation technique. To cement the dissolved Pb and Zn in leaching pulp, zero-valent aluminum (ZVAl) was added during ZPLRs leaching in the hydrochloric (HCl)–sodium chloride (NaCl) solution. The resulting cemented metals were agglomerated and separated by sieving. Lead removal increased with increasing both NaCl and HCl concentrations. However, when ZVAl was added, significant Pb removal was achieved at a low concentration. Zinc was not cemented out of the pulp using ZVAl and its recovery from ZPLRs was dependent on the HCl concentration only. By applying a concurrent dissolution and cementation technique, both Pb and Zn were removed using a low concentration of NaCl, and most importantly Pb—the most toxic metal in ZPLRs—was captured and separated before the solid-liquid separation, hence, eliminating the need for extensive washing of the generated residues to remove the inherent residual solution.
• Quantitative elucidation of maternal-to-fetal transfer of neonicotinoid pesticide clothianidin and its metabolites in mice.

  Shuji Ohno, Yoshinori Ikenaka, Kanoko Onaru, Shizuka Kubo, Nanami Sakata, Tetsushi Hirano, Youhei Mantani, Toshifumi Yokoyama, Keisuke Takahashi, Keisuke Kato, Koji Arizono, Takahiro Ichise, Shouta M M Nakayama, Mayumi Ishizuka, Nobuhiko Hoshi

  Toxicology letters 322 32 - 38 2020年04月01日 [査読有り][通常論文]
   

  Neonicotinoids (NNs), a widely used class of systemic pesticides, are regarded as exhibiting selective toxicity in insects. However, NNs are suspected of exerting adverse effects on mammals as well, including humans. To date, only adult male animal models have been subjected to general toxicity studies of NNs; fetuses have yet to be considered in this context. Here, we focused on the NN clothianidin (CLO) for the first quantitative LC-MS/MS analysis of maternal-to-fetal transfer and residual property of once-daily (single or multiple days), orally administered CLO and its metabolites in mice. The results revealed the presence of CLO and its five metabolites at approximately the same respective blood levels in both dams and fetuses. In the dams, CLO showed a peak value 1 h after administration, after which levels rapidly decreased at 3 and 6 h. In the fetuses of each group, levels of CLO were almost the same as those observed in the corresponding dams. The present results clearly demonstrated rapid passage of CLO through the placental barrier. However, metabolite-dependent differences observed in blood pharmacokinetics and residual levels. This is the first quantitative demonstration of the presence of CLO and its metabolites in fetal mouse blood.
• Current trends of blood lead levels, distribution patterns and exposure variations among household members in Kabwe, Zambia.

  John Yabe, Shouta Mm Nakayama, Hokuto Nakata, Haruya Toyomaki, Yared B Yohannes, Kaampwe Muzandu, Andrew Kataba, Golden Zyambo, Masato Hiwatari, Daiju Narita, Daichi Yamada, Peter Hangoma, Nosiku Sipilanyambe Munyinda, Tiza Mufune, Yoshinori Ikenaka, Kennedy Choongo, Mayumi Ishizuka

  Chemosphere 243 125412 - 125412 2020年03月 [査読有り][通常論文]
   

  Childhood lead (Pb) poisoning has devastating effects on neurodevelopment and causes overt clinical signs including convulsions and coma. Health effects including hypertension and various reproductive problems have been reported in adults. Historical Pb mining in Zambia's Kabwe town left a legacy of environmental pollution and childhood Pb poisoning. The current study aimed at establishing the extent of Pb poisoning and exposure differences among family members in Kabwe as well as determining populations at risk and identify children eligible for chelation therapy. Blood samples were collected in July and August 2017 from 1190 household members and Pb was measured using a portable LeadCare-II analyser. Participants included 291 younger children (3-months to 3-years-old), 271 older children (4-9-years-old), 412 mothers and 216 fathers from 13 townships with diverse levels of Pb contamination. The Blood Lead Levels (BLL) ranged from 1.65 to 162  μg/dL, with residents from Kasanda (mean 45.7  μg/dL) recording the highest BLL while Hamududu residents recorded the lowest (mean 3.3  μg/dL). Of the total number of children sampled (n = 562), 23% exceeded the 45  μg/dL, the threshold required for chelation therapy. A few children (5) exceeded the 100  μg/dL whereas none of the parents exceeded the 100  μg/dL value. Children had higher BLL than parents, with peak BLL-recorded at the age of 2-years-old. Lead exposure differences in Kabwe were attributed to distance and direction from the mine, with younger children at highest risk. Exposure levels in parents were equally alarming. For prompt diagnosis and treatment, a portable point-of-care devise such as a LeadCare-II would be preferable in Kabwe.
• In Vivo Accumulation of Plastic-Derived Chemicals into Seabird Tissues.

  Kosuke Tanaka, Yutaka Watanuki, Hideshige Takada, Mayumi Ishizuka, Rei Yamashita, Mami Kazama, Nagako Hiki, Fumika Kashiwada, Kaoruko Mizukawa, Hazuki Mizukawa, David Hyrenbach, Michelle Hester, Yoshinori Ikenaka, Shouta M M Nakayama

  Current biology : CB 30 4 723 - 728 2020年02月24日 [査読有り][通常論文]
   

  Plastic debris is ubiquitous and increasing in the marine environment [1]. A wide range of marine organisms ingest plastic, and its impacts are of growing concern [2]. Seabirds are particularly susceptible to plastic pollution because of high rates of ingestion [3]. Because marine plastics contain an array of hazardous compounds, the chemical impacts of ingestion are concerning. Several studies on wild seabirds suggested accumulation of plastic-derived chemicals in seabird tissues [4-7]. However, to date, the evidence has all been indirect [4-7], and it is unclear whether plastic debris is the source of these pollutants. To obtain direct evidence for the transfer and accumulation of plastic additives in the tissues of seabirds, we conducted an in vivo plastic feeding experiment. Environmentally relevant exposure of plastics compounded with one flame retardant and four ultraviolet stabilizers to streaked shearwater (Calonectris leucomelas) chicks in semi-field conditions resulted in the accumulation of the additives in liver and adipose fat of 91 to 120,000 times the rate from the natural diet. Additional monitoring of six seabird species detected these chemical additives only in those species with high plastic ingestion rates, suggesting that plastic debris can be a major pathway of chemical pollutants into seabirds. These findings provide direct evidence of seabird exposure to plastic additives and emphasize the role of marine debris ingestion as a source of chemical pollution in marine organisms.
• Avian interspecific differences in VKOR activity and inhibition: Insights from amino acid sequence and mRNA expression ratio of VKORC1 and VKORC1L1.

  Shouta M M Nakayama, Ayuko Morita, Yoshinori Ikenaka, Yusuke K Kawai, Kensuke P Watanabe, Chihiro Ishii, Hazuki Mizukawa, Yared B Yohannes, Keisuke Saito, Yukiko Watanabe, Masaki Ito, Natsuo Ohsawa, Mayumi Ishizuka

  Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 228 108635 - 108635 2020年02月 [査読有り][通常論文]
   

  Worldwide use of anticoagulant rodenticides (ARs) for rodents control has frequently led to secondary poisoning of non-target animals, especially raptors. In order to suggest some factors that may help considering the mechanism of the incidents, this study focused on the avian vitamin K 2, 3-epoxide reductase (VKOR) that is the target protein of ARs. We addressed the interspecific differences in VKOR activity and inhibition related to amino acid sequence and mRNA expression of VKORC1 and VKORC1-like1 (VKORC1L1). Poultry have been considered to be more tolerant to ARs than mammals. However, VKOR activity of owls, hawks, falcon and surprisingly, canaries, was lower and inhibited by warfarin more easily than that of chickens and turkeys. The amino acid sequence of VKORC1 and VKORC1L1 implied that the value of Ki for VKOR activity to ARs could depend on the amino acid at position 140 in the TYX warfarin-binding motif in VKORC1, and other amino acid mutations in VKORC1L1. The mRNA expression ratio of VKORC1:VKORC1L1 differed between turkey (8:1) and chicken (2:3) liver. VKORC1L1 has been reported to be resistant to warfarin compared to VKORC1. Hence, both the Ki of specific VKORC1 and VKORC1L1, and the mRNA expression ratio would cause avian interspecific difference of the VKOR inhibition. Our study also suggested the high inhibition of VKOR activities in raptors and surprisingly that in canaries as well. These factors are the most likely to contribute to the high sensitivity to ARs found in raptors.
• 有機および無機土壌改良に応答したザンビアのKabwe鉱山付近で成長したトウモロコシにおける鉛,亜鉛およびカドミウムの蓄積および関連する健康リスク【JST・京大機械翻訳】

  Mwilola Patricia N., Mukumbuta Ikabongo, Mukumbuta Ikabongo, Shitumbanuma Victor, Chishala Benson H., Uchida Yoshitaka, Nakata Hokuto, Nakayama Shouta, Ishizuka Mayumi

  International Journal of Environmental Research and Public Health (Web) 17 23 2020年 

  Health risks due to heavy metal (HM) contamination is of global concern. Despite concerns of high levels of HMs in soils near Kabwe mine in Zambia, edible crop production is common, posing potential health risks. This study assessed the potential of chicken manure (CM), triple superphosphate (TSP) and a blended fertilizer (BF; consisting of Nitrogen, Phosphorous and Potassium (NPK) fertilizer and composted chicken manure) to reduce lead (Pb), zinc (Zn) and cadmium (Cd) in soils and their accumulation in maize grown near the Kabwe mine. Maize was grown to maturity and its HM concentrations and associated health risk indices were calculated. All soil amendments decreased bioavailable soil Pb concentrations by 29-36%, but only CM decreased Zn, while the amendments increased or had no effect on Cd concentrations compared to the control. The amendments reduced Pb (>25%) and Zn concentrations (>18%) in the maize stover and grain. However, Cd concentrations in maize grain increased in the BF and TSP treatments. Bioaccumulation factors showed that Cd had the highest mobility from the soil into maize stover and grain, indicating the need for greater attention on Cd in Kabwe despite its apparently lower soil concentration compared to Pb and Zn. The hazard quotients for Pb and Cd were much greater than one, indicating a high risk of possible exposure to toxic levels by people consuming maize grain grown in this area. This study demonstrated the significant potential of manure and phosphate-based amendments to reduce Pb and Zn, and to some extent Cd, uptake in maize grain and consequently reduce associated health risks.
• デカブロモジフェニルエーテル(BDE-209)の慢性曝露後のネコにおける肝チトクロームP450発現の変化

  KHIDKHAN Kraisiri, MIZUKAWA Hazuki, MIZUKAWA Hazuki, IKENAKA Yoshinori, IKENAKA Yoshinori, NAKAYAMA Shouta M. M., NOMIYAMA Kei, YOKOYAMA Nozomu, ICHII Osamu, ICHII Osamu, TAKIGUCHI Mitsuyoshi, TANABE Shinsuke, ISHIZUKA Mayumi

  Journal of Veterinary Medical Science (Web) 82 7 978 - 982 2020年 [査読有り][通常論文]
   

  The knowledge of cytochrome P450 (CYP) expression involved in chemical exposure are necessary in clinical applications for the medication and prediction of adverse effects. The aim of this study was to evaluate the mRNA expression of CYP1-CYP3 families in cats exposed to BDE-209 for one year. All selected CYP isoforms showed no significant difference in mRNA expressions between control and exposure groups, however, CYP3A12 and CYP3A131 revealed tend to be two times higher in the exposure group compared to control group. The present results indicate that the chronic exposure of BDE209 could not alter CYP expression in the liver of cats. This result considered caused by the deficiency of CYP2B subfamily which is major metabolism enzyme of polybrominated diphenyl ethers (PBDEs) in cat.
• Bioimaging of Pb and STIM1 in mice liver, kidney and brain using Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) and immunohistochemistry.

  Masao Togao, Shouta M M Nakayama, Yoshinori Ikenaka, Hazuki Mizukawa, Yoshiki Makino, Ayano Kubota, Takehisa Matsukawa, Kazuhito Yokoyama, Takafumi Hirata, Mayumi Ishizuka

  Chemosphere 238 124581 - 124581 2020年01月 [査読有り][通常論文]
   

  Lead (Pb) pollution is one of the most serious environmental problems and has attracted worldwide attention. Pb causes hematological, central nervous system, as well as renal toxicity, and so on. Although many investigations about Pb in blood to evaluate pollution status and toxic effects have been reported, there are open question about biological behavior of Pb. In order to reveal any toxicological mechanisms or influences, we focused on the local distribution of Pb in mice organs. Lead acetate (100 mg/L and 1000 mg/L) in drinking water were given to the BALB/c mice (male, seven weeks of age, N = 24) for three weeks. Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) analysis revealed a homogenous distribution of Pb in the liver and inhomogeneous distribution in the kidney and brain. The hippocampus, thalamus, and hypothalamus had higher concentrations than other areas such as the white matter. Surprisingly, in the kidney, Pb tended to accumulate in the medulla rather than the cortex, strongly suggesting that high sensitivity areas and high accumulation areas differ. Moreover, distribution of stromal interacting protein 1 (STIM1) which is candidate gene of Pb pathway to the cells was homogenous in the liver and kidney whereas inhomogeneous in the brain. In contrast to our hypothesis, interestingly, Pb exposure under the current condition did not induce mRNA expressions for any candidate channel or transporter genes. Thus, further study should be conducted to elucidate the local distribution of Pb and other toxic metals, and pathway that Pb takes to the cells.
• Occurrence and concentrations of chemical additives in plastic fragments on a beach on the island of Kauai, Hawaii.

  Kosuke Tanaka, Hideshige Takada, Yoshinori Ikenaka, Shouta M M Nakayama, Mayumi Ishizuka

  Marine pollution bulletin 150 110732 - 110732 2020年01月 [査読有り][通常論文]
   

  In the ocean, plastic debris containing chemical additives is fragmented into smaller pieces that can be ingested by a wide range of organisms, potentially exposing them to additives. However, the levels of additives retained in marine plastic fragments have rarely been assessed. In this study, 141 plastic fragments from a beach in Kauai were analyzed piece-by-piece for 12 compounds, including UV stabilizers and brominated flame retardants. UV stabilizers (UV-326, UV-328, UV-327, and BP-12) were found in 13% of "small" fragments (4-7 mm) with levels of up to 315 μg/g and in 33% of "large" fragments (15-80 mm) with levels of up to 1130 μg/g. This observation suggests that exhaustive leaching of additives does not occur during fragmentation and that significant levels of additives, comparable to those of the original products, can be retained in fragments of marine plastic, indicating their importance as a vector of chemical additive exposure.
• Dichlorodiphenyltrichloroethane (DDT) levels in rat livers collected from a malaria vector control region.

  Kodai Motohira, Yoshinori Ikenaka, Yared Beyene Yohannes, Shouta M M Nakayama, Victor Wepener, Nico J Smit, Johan H J VAN Vuren, Ana Catarina Sousa, Alex Ajeh Enuneku, Emmanuel Temiotan Ogbomida, Mayumi Ishizuka

  The Journal of veterinary medical science 81 11 1575 - 1579 2019年11月14日 [査読有り][通常論文]
   

  Dichlorodiphenyltrichloroethane (DDT) is an organochlorine insecticide that has been used for indoor residual spraying for the control of mosquito-borne diseases including malaria. However, due to its toxicity and environmental persistence, there are concerns about its potential deleterious effects in humans and wildlife. Therefore, the current study aimed to monitor and estimate the level of DDTs in human communities. The accumulation of DDT and its metabolites was evaluated in house rat (as sentinel) livers collected in an area where DDT was sprayed. DDTs were measured using a gas chromatography / Electron Capture Detector. The results revealed high concentrations of DDTs in the rat livers and the levels of DDTs were similar to findings reported from the same area in 2014.
• Effects of the organochlorine p,p'-DDT on MCF-7 cells: Investigating metabolic and immune modulatory transcriptomic changes.

  Lesa A Thompson, Yoshinori Ikenaka, Wageh Sobhy Darwish, Shouta M M Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  Environmental toxicology and pharmacology 72 103249 - 103249 2019年11月 [査読有り][通常論文]
   

  The organochlorine pesticide dichloro-diphenyl-trichloroethane (DDT) is persistent in the environment and leads to adverse human health effects. High levels in breast milk pose a threat to both breast tissue and nursing infants. The objectives of this study were to investigate DDT-induced transcriptomic alterations in enzymes and transporters involved in xenobiotic metabolism, immune responses, oxidative stress markers, and cell growth in a human breast cancer cell line. MCF-7 cells were exposed to both environmentally-relevant and previously-tested concentrations of p,p'-DDT in a short-term experiment. Significant up-regulation of metabolizing enzymes and transporters (ACHE, GSTO1, NQO1 and ABCC2) and oxidative stress markers (CXCL8, HMOX-1, NFE2L2 and TNF) was clearly observed. Conversely, UGT1A6, AHR and cell growth genes (FGF2 and VEGFA) were severely down-regulated. Identification of these genes helps to identify mechanisms of p,p'-DDT action within cells and may be considered as useful biomarkers for exposure to DDT contamination.
• Effects of PCB exposure on serum thyroid hormone levels in dogs and cats.

  Kohki Takaguchi, Hiroyuki Nishikawa, Hazuki Mizukawa, Rumi Tanoue, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Shouta M M Nakayama, Yoshinori Ikenaka, Tatsuya Kunisue, Mayumi Ishizuka, Shinsuke Tanabe, Hisato Iwata, Kei Nomiyama

  The Science of the total environment 688 1172 - 1183 2019年10月20日 [査読有り][通常論文]
   

  Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) might disrupt thyroid function. However, there is no clear evidence of PCB exposure disrupting thyroid hormone (TH) homeostasis in dogs and cats. The present study conducted in vivo experiments to evaluate the effects of a mixture of 12 PCB congeners (CB18, 28, 70, 77, 99, 101, 118, 138, 153, 180, 187 and 202, each congener 0.5 mg/kg BW, i.p. administration) on serum TH levels in male dogs (Canis lupus familiaris) and male cats (Felis silvestris catus). In PCB-exposed dogs, the time courses of higher-chlorinated PCBs and L-thyroxine (T4)-like OH-PCBs (4-OH-CB107 and 4-OH-CB202) concentrations were unchanged or tended to increase, whereas those of lower-chlorinated PCBs and OH-PCBs tended to decrease after 24 h. In PCB-exposed cats, concentrations of PCBs increased until 6 h and then remained unchanged. The levels of lower-chlorinated OH-PCBs including 4'-OH-CB18 increased until 96 h and then decreased. In PCB-exposed dogs, free T4 concentrations were higher than those in the control group at 48 and 96 h after PCB administration and positively correlated with the levels of T4-like OH-PCBs, suggesting competitive binding of T4 and T4-like OH-PCBs to a TH transporter, transthyretin. Serum levels of total T4 and total 3,3',5-triiodo-L-thyronine (T3) in PCB-exposed dogs were lower than in the control group at 24 and 48 h and negatively correlated with PCB concentrations, implying that PCB exposure enhanced TH excretion by increasing TH uptake and TH conjugation enzyme activities in the dog liver. In contrast, no obvious changes in TH levels were observed in PCB-exposed cats. This could be explained by the lower levels of T4-like OH-PCBs and lower hepatic conjugation enzyme activities in cats compared with dogs. Different effects on serum TH levels in PCB-exposed dogs and cats are likely to be attributable to species-specific PCB and TH metabolism.
• Bioaccumulation of persistent organic pollutants and their trophic transfer through the food web: Human health risks to the rural communities reliant on fish from South Africa's largest floodplain

  C.M. Volschenk, R. Gerber, M.T. Mkhonto, Y. Ikenaka, Y.B. Yohannes, S. Nakayama, M. Ishizuka, J.H.J. van Vuren, V. Wepener, N.J. Smit

  Science of The Total Environment 685 1116 - 1126 2019年10月
• How toxic is a non-toxic nanomaterial: Behaviour as an indicator of effect in Danio rerio exposed to nanogold.

  Tarryn L Botha, Sarel J Brand, Yoshinori Ikenaka, Shouta M M Nakayama, Mayumi Ishizuka, Victor Wepener

  Aquatic toxicology (Amsterdam, Netherlands) 215 105287 - 105287 2019年10月 [査読有り][通常論文]
   

  Gold nanoparticles are used as drug delivery vectors based on the assumption that they have low toxicity. Literature has, however, produced conflicting results over the last few years. As such, this study aimed to investigate the toxicological effects of nanogold (nAu) on several indicators that range from subcellular to whole-organism level. Gene regulation, changes in oxidative stress biomarkers and swimming performance were assessed in Danio rerio (zebrafish) following exposures to nAu. Adult zebrafish were exposed in vivo to nAu for 96 h and swimming performance measured post-exposure. Liver tissue was collected for DNA microarray and Real-Time Polymerase Chain Reactions (RT-PCR) analyses to determine changes in gene expression (catalase, superoxide dismutase and metallothioneins) and protein biomarker analyses (catalase, superoxide dismutase, acetylcholine esterase, malondialdehyde, cellular energy allocation and metallothionein) were performed on whole-body samples. Swimming behaviour was assessed in 1.1 L Tecniplast™ tanks for a period of six hours and videos were analysed using Noldus EthoVision software. Critical swimming speed was measured in a Loligo® swimming tunnel. The DNA microarray revealed that fish exposed to 20 mg/L differed most from the control group. At 20 mg/L there was a significant increase in gene expression for all genes analysed but this didn't translate to significant responses in protein biomarker levels except for an increase in protein carbonyl formation. The behaviour results demonstrated significant changes in distance moved, swimming speed, acceleration bouts, zone alterations and time spent within the top zone - responses that are usually observed in fish responding to toxicological stress. Furthermore, the critical swimming speed of exposed fish was decreased significantly compared to the control. Since swimming performance and social interaction among zebrafish is essential to their survival, whole-organism behaviour that suggests a toxicological response after exposure to nAu is in agreement with the genetic responses measured in this study.
• One year exposure to Cd- and Pb-contaminated soil causes metal accumulation and alteration of global DNA methylation in rats.

  Shouta M M Nakayama, Hokuto Nakata, Yoshinori Ikenaka, John Yabe, Balazs Oroszlany, Yared B Yohannes, Nesta Bortey-Sam, Kaampwe Muzandu, Kennedy Choongo, Takeshi Kuritani, Mitsuhiro Nakagawa, Mayumi Ishizuka

  Environmental pollution (Barking, Essex : 1987) 252 Pt B 1267 - 1276 2019年09月 [査読有り][通常論文]
   

  Metal pollution has been associated with anthropogenic activities, such as effluents and emissions from mines. Soil could be exposure route of wild rats to metals, especially in mining areas. The aim of this study was to verify whether soil exposure under environmentally relevant circumstances results in metal accumulation and epigenetic modifications. Wistar rats were divided to three groups: 1) control without soil exposure, 2) low-metal exposure group exposed to soil containing low metal levels (Pb: 75 mg/kg; Cd: 0.4), and 3) high-metal exposure group exposed to soil (Pb: 3750; Cd: 6). After 1 year of exposure, the metal levels, Pb isotopic values, and molecular indicators were measured. Rats in the high-group showed significantly greater concentrations of Pb and Cd in tissues. Higher accumulation factors (tissue/soil) of Cd than Pb were observed in the liver, kidney, brain, and lung, while the factor of Pb was higher in the tibia. The obtained results of metal accumulation ratios (lung/liver) and stable Pb isotope ratios in the tissues indicated that the respiratory exposure would account for an important share of metal absorption into the body. Genome-wide methylation status and DNA methyltransferase (Dnmt 3a/3b) mRNA expressions in testis were higher in the high-group, suggesting that exposure to soil caused metal accumulation and epigenetic alterations in rats.
• Solidification of sand by Pb(II)-tolerant bacteria for capping mine waste to control metallic dust: Case of the abandoned Kabwe Mine, Zambia.

  Wilson Mwandira, Kazunori Nakashima, Satoru Kawasaki, Mayumi Ito, Tsutomu Sato, Toshifumi Igarashi, Meki Chirwa, Kawawa Banda, Imasiku Nyambe, Shouta Nakayama, Hokuto Nakata, Mayumi Ishizuka

  Chemosphere 228 17 - 25 2019年08月 [査読有り][通常論文]
   

  Environmental impacts resulting from historic lead and zinc mining in Kabwe, Zambia affect human health due to the dust generated from the mine waste that contains lead, a known hazardous pollutant. We employed microbially induced calcium carbonate precipitation (MICP), an alternative capping method, to prevent dust generation and reduce the mobility of contaminants. Pb-resistant Oceanobacillus profundus KBZ 1-3 and O. profundus KBZ 2-5 isolated from Kabwe were used to biocement the sand that would act as a cover to prevent dust and water infiltration. Sand biocemented by KBZ 1-3 and KBZ 2-5 had maximum unconfined compressive strength values of 3.2 MPa and 5.5 MPa, respectively. Additionally, biocemented sand exhibited reduced water permeability values of 9.6 × 10-8 m/s and 8.9 × 10-8 m/s for O. profundus KBZ 1-3 and KBZ 2-5, respectively, which could potentially limit the entrance of water and oxygen into the dump, hence reducing the leaching of heavy metals. We propose that these isolates represent an option for bioremediating contaminated waste by preventing both metallic dust from becoming airborne and rainwater from infiltrating into the waste. O. profundus KBZ 1-3 and O. profundus KBZ 2-5 isolated form Kabwe represent a novel species that has, for the first time, been applied in a bioremediation study.
• Zinc and Lead Biosorption by Oceanobacillus Profundus Kbz 3-2: a Bacterial Strain Resistant to Metals Isolated from Metal polluted Soils in Kabwe, Zambia

  Wilson Mwandira, Kazunori Nakashima, Satoru Kawasaki, Mayumi Ito, Tsutomu Sato, Toshifumi Igarashi, Meki Chirwa, Kawawa Banda, Imasiku Nyambe, Shouta Nakayama, Mayumi Ishizuka

  Proceedings of the 14th Asian Congress on Biotechnology (ACB2019) 2019年07月 [査読有り][通常論文]
  
• ネオニコチノイド系殺虫剤と農薬の現状と今後の展望〜毒性学・農学・行政の視点から〜 ネオニコチノイド系殺虫剤の曝露実態の解明と毒性評価

  池中 良徳, 一瀬 貴大, Nimako Collins, 中山 翔太, 平野 哲史, 市川 剛, 加藤 恵介, 高橋 圭介, 長谷川 浩, 平 久美子, 有薗 幸司, 星 信彦, 藤岡 一俊, 石塚 真由美

  The Journal of Toxicological Sciences 44 Suppl. S53 - S53 (一社)日本毒性学会 2019年06月
• Evidence of impacts from DDT in pelican, cormorant, stork, and egret eggs from KwaZulu-Natal, South Africa.

  H Bouwman, Y B Yohannes, S M M Nakayama, K Motohira, M Ishizuka, M S Humphries, V van der Schyff, M du Preez, A Dinkelmann, Y Ikenaka

  Chemosphere 225 647 - 658 2019年06月 

  DDT remains in use for malaria control in South Africa. We quantified DDTs in aquatic bird eggs from the highly biodiverse northern KwaZulu-Natal, a province of South Africa where DDT has been used for more than 80 years for malaria control. Pelican eggs had the highest ΣDDT concentration (7200 ng/g lipid mass; lm), Little Egret eggs had 6900 ΣDDT lm, African Openbill eggs had 3400 ng/g lm ΣDDT, and White-breasted Cormorant had 2400 ng/g lm. All species had non-significantly different mean concentrations of o,p'-DDT, p,p'-DDT, and ΣDDT, but with significant differences for p,p-DDE, o,p'-DDD, p,p'-DDD, %DDT, %DDD, and %lipid. The thinnest pelican eggshell (0.40 mm) had a ΣDDT concentration of 3300 ng/g lm.; the thickest shell (0.96 mm) had the lowest ΣDDT concentration at 29 ng/g lm; a 58% difference. Linear regressions of concentrations with shell thickness for the pelican eggs were significant for p,p'-DDE and p,p'-DDD, indicating risk of reproductive impairment. Compositional profiles indicate different food webs for the different species. DDT concentrations were lower than from another DDT-sprayed locality in South Africa, possible linked to differences in hydrology and rainfall. We conclude that significant ecotoxic threats associated with DDT remain in this area, and possibly threatens birds from less polluted areas. Our findings suggest continued negative human health and environmental impacts from DDT. There is an urgency to move away from DDT as quickly as possible; alternatively, to implement practices that prevent emissions of DDT to the environment while protecting human life.
• Efficacy of biocementation of lead mine waste from the Kabwe Mine site evaluated using Pararhodobacter sp.

  Wilson Mwandira, Kazunori Nakashima, Satoru Kawasaki, Mayumi Ito, Tsutomu Sato, Toshifumi Igarashi, Kawawa Banda, Meki Chirwa, Imasiku Nyambe, Shouta Nakayama, Mayumi Ishizuka

  Environmental science and pollution research international 26 15 15653 - 15664 2019年05月 [査読有り][通常論文]
   

  Biocementation of hazardous waste is used in reducing the mobility of contaminants, but studies on evaluating its efficacy have not been well documented. Therefore, to evaluate the efficacy of this method, physicochemical factors affecting stabilized hazardous products of in situ microbially induced calcium carbonate precipitation (MICP) were determined. The strength and leach resistance were investigated using the bacterium Pararhodobacter sp. Pb-contaminated kiln slag (KS) and leach plant residue (LPR) collected from Kabwe, Zambia, were investigated. Biocemented KS and KS/LPR had leachate Pb concentrations below the detection limit of < 0.001 mg/L, resisted slaking, and had maximum unconfined compressive strengths of 8 MPa for KS and 4 MPa for KS/LPR. Furthermore, biocemented KS and KS/LPR exhibited lower water absorption coefficient values, which could potentially reduce the water transportation of Pb2+. The results of this study show that MICP can reduce Pb2+ mobility in mine wastes. The improved physicochemical properties of the biocemented materials, therefore, indicates that this technique is an effective tool in stabilizing hazardous mine wastes and, consequently, preventing water and soil contamination.
• Characterization of function and genetic feature of UDP-glucuronosyltransferase in avian species

  Yusuke K. Kawai, So Shinya, Yoshinori Ikenaka, Aksorn Saengtienchai, Takamitsu Kondo, Wageh Sobhy Darwish, Shota M.M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 217 5 - 14 2019年03月
• A review: poisoning by anticoagulant rodenticides in non-target animals globally.

  Shouta M M Nakayama, Ayuko Morita, Yoshinori Ikenaka, Hazuki Mizukawa, Mayumi Ishizuka

  The Journal of veterinary medical science 81 2 298 - 313 2019年02月28日 [査読有り][通常論文]
   

  Worldwide use of anticoagulant rodenticides (ARs) for rodents control has frequently led to secondary poisoning of non-target animals, especially raptors. In spite of the occurrence of many incidents of primary or secondary AR-exposure and poisoning of non-target animals, these incidents have been reported only for individual countries, and there has been no comprehensive worldwide study or review. Furthermore, the AR exposure pathway in raptors has not yet been clearly identified. The aim of this review is therefore to comprehensively analyze the global incidence of primary and secondary AR-exposure in non-target animals, and to explore the exposure pathways. We reviewed the published literature, which reported AR residues in the non-target animals between 1998 and 2015, indicated that various raptor species had over 60% AR- detection rate and have a risk of AR poisoning. According to several papers studied on diets of raptor species, although rodents are the most common diets of raptors, some raptor species prey mainly on non-rodents. Therefore, preying on targeted rodents does not necessarily explain all causes of secondary AR-exposure of raptors. Since AR residue-detection was also reported in non-target mammals, birds, reptiles and invertebrates, which are the dominant prey of some raptors, AR residues in these animals, as well as in target rodents, could be the exposure source of ARs to raptors.
• Biotransport of metallic trace elements from marine to terrestrial ecosystems by seabirds

  A. Shoji, K. H. Elliott, S. Aris-Brosou, H. Mizukawa, S. M.M. Nakayama, Y. Ikenaka, M. Ishizuka, T. Kuwae, K. Watanabe, J. Escoruela Gonzalez, Y. Watanuki

  Environmental Toxicology and Chemistry 38 1 106 - 114 2019年01月 

  Physical systems, such as currents and winds, have traditionally been considered responsible for transporting contaminants. Although evidence is mounting that animals play a role in this process through their movements, we still know little about how such contaminant biotransport occurs and the extent of effects at deposition sites. In the present study, we address this question by studying how rhinoceros auklets (Cerorhinca monocerata), a seabird that occurs in immense colonies (∼300 000 pairs at our study site, Teuri Island), affect contaminant levels at their colony and at nearby sites. More specifically, we hypothesize that contaminants are transported and deposited by seabirds at their colony and that these contaminants are passed on locally to the terrestrial ecosystem. To test this hypothesis, we analyzed the concentration of 9 heavy metal and metalloids, as well as δ 13 C and δ 15 N stable isotopes, in bird tissues, plants, and soil, both within and outside of the colony. The results show that rhinoceros auklets transport marine-derived mercury (Hg), possibly from their wintering location, and deposit Hg via their feces at their breeding site, thereby contaminating plants and soils within the breeding colony. The present study confirms not only that animals can transport contaminants from marine to terrestrial ecosystems, potentially over unexpectedly long distances, but also that bird tissues contribute locally to plant contamination. Environ Toxicol Chem 2019;38:106–114. © 2018 SETAC.
• Exposures of children to neonicotinoids in pine wilt disease control areas.

  Yoshinori Ikenaka, Yuichi Miyabara, Takahiro Ichise, Shouta Nakayama, Collins Nimako, Mayumi Ishizuka, Chiharu Tohyama

  Environmental toxicology and chemistry 38 1 71 - 79 2019年01月 [査読有り][通常論文]
   

  Neonicotinoid insecticides that have been on the market since 1992 have been used globally including in Japan. Because they are sprayed over forests and agricultural areas, inadvertent toxicity in nontarget insects (especially honey bees) and humans is a matter of public concern. However, information on exposure levels and potential health impacts of neonicotinoids in children living around sprayed areas is scarce. Thus, we determined neonicotinoid exposure levels in children living in communities where thiacloprid was used to control pine wilt disease. A total of 46 children (23 males and 23 females) were recruited for the present study, and informed written consent was obtained from their guardians. Urine specimens were collected before, during, and after insecticide spraying events; and atmospheric particulate matter was also collected. Concentrations of thiacloprid and 6 other neonicotinoid compounds were determined in urine samples and in atmospheric particulate matter specimens using liquid chromatography-electrospray ionization-tandem mass spectrometry. In urine specimens, thiacloprid concentrations were <0.13 μg/L and were detectable in approximately 30% of all samples. Concentrations of the other neonicotinoids, N-dm-acetamiprid, thiamethoxam, dinotefuran, and clothianidin, were 18.7, 1.92, 72.3, and 6.02 µg/L, respectively. Estimated daily intakes of these neonicotinoids were then calculated from urinary levels; although the estimated daily intakes of the neonicotinoids were lower than current acceptable daily intake values, the children were found to be exposed to multiple neonicotinoids on a daily basis. Environ Toxicol Chem 2019;38:71-79. © 2018 SETAC.
• LC-ESI/MS/MS analysis of neonicotinoids in urine of very low birth weight infants at birth.

  Go Ichikawa, Ryota Kuribayashi, Yoshinori Ikenaka, Takahiro Ichise, Shouta M M Nakayama, Mayumi Ishizuka, Kumiko Taira, Kazutoshi Fujioka, Toshimi Sairenchi, Gen Kobashi, Jean-Marc Bonmatin, Shigemi Yoshihara

  PloS one 14 7 e0219208  2019年 [査読有り][通常論文]
   

  OBJECTIVES: Neonicotinoid insecticides are widely used systemic pesticides with nicotinic acetylcholine receptor agonist activity that are a concern as environmental pollutants. Neonicotinoids in humans and the environment have been widely reported, but few studies have examined their presence in fetuses and newborns. The objective of this study is to determine exposure to neonicotinoids and metabolites in very low birth weight (VLBW) infants. METHODS: An analytical method for seven neonicotinoids and one neonicotinoid metabolite, N-desmethylacetamiprid (DMAP), in human urine using LC-ESI/MS/MS was developed. This method was used for analysis of 57 urine samples collected within 48 hours after birth from VLBW infants of gestational age 23-34 weeks (male/female = 36/21, small for gestational age (SGA)/appropriate gestational age (AGA) = 6/51) who were admitted to the neonatal intensive care unit of Dokkyo Hospital from January 2009 to December 2010. Sixty-five samples collected on postnatal day 14 (M/F = 37/22, SGA/AGA = 7/52) were also analyzed. RESULTS: DMAP, a metabolite of acetamiprid, was detected in 14 urine samples collected at birth (24.6%, median level 0.048 ppb) and in 7 samples collected on postnatal day 14 (11.9%, median level 0.09 ppb). The urinary DMAP detection rate and level were higher in SGA than in AGA infants (both p<0.05). There were no correlations between the DMAP level and infant physique indexes (length, height, and head circumference SD scores). CONCLUSION: These results provide the first evidence worldwide of neonicotinoid exposure in newborn babies in the early phase after birth. The findings suggest a need to examine potential neurodevelopmental toxicity of neonicotinoids and metabolites in human fetuses.
• ポリ塩化ビフェニル曝露に関連したネコのチトクロームP450遺伝子の組織分布と特性化【JST・京大機械翻訳】

  Khidkhan Kraisiri, Mizukawa Hazuki, Mizukawa Hazuki, Ikenaka Yoshinori, Ikenaka Yoshinori, Nakayama Shouta M.M., Nomiyama Kei, Yokoyama Nozomu, Ichii Osamu, Darwish Wageh Sobhy, Darwish Wageh Sobhy, Takiguchi Mitsuyoshi, Tanabe Shinsuke, Ishizuka Mayumi

  Comparative Biochemistry and Physiology. C. Toxicology & Pharmacology 226 108613 - 108613 2019年 [査読有り][通常論文]
   

  Cats have been known to be extremely sensitive to chemical exposures. To understand these model species' sensitivity to chemicals and their toxicities, the expression profiles of xenobiotic-metabolizing enzymes should be studied. Unfortunately, the characterization of cytochrome P450 (CYP), the dominant enzyme in phase I metabolism, in cats has not extensively been studied. Polychlorinated biphenyls (PCBs) are known as CYP inducers in animals, but the information regarding the PCB-induced CYP expression in cats is limited. Therefore, in the present study, we aimed to elucidate the mRNA expression of the CYP1-CYP3 families in the cat tissues and to investigate the CYP mRNA expression related to PCB exposure. In cats, the greatest abundance of CYP1-CYP3 (CYP1A2, CYP2A13, CYP2C41, CYP2D6, CYP2E1, CYP2E2, CYP2F2, CYP2F5, CYP2J2, CYP2U1, and CYP3A132) was expressed in the liver, but some extrahepatic isozymes were found in the kidney (CYP1A1), heart (CYP1B1), lung (CYP2B11 and CYP2S1) and small intestine (CYP3A131). In cats, CYP1A1, CYP1A2 and CYP1B1 were significantly upregulated in the liver as well as in several tissues exposed to PCBs, indicating that these CYPs were distinctly induced by PCBs. The strong correlations between 3,3',4,4'-tetrachlorobiphenyl (CB77) and CYP1A1 and CYP1B1 mRNA expressions were noted, demonstrating that CB77 could be a potent CYP1 inducer. In addition, these CYP isoforms could play an essential role in the PCBs biotransformation, particularly 3-4 Cl-PCBs, because a high hydroxylated metabolite level of 3-4 Cl-OH-PCBs was observed in the liver.
• Characterization and imaging of lead distribution in bones of lead-exposed birds by ICP-MS and LA-ICP-MS.

  Chihiro Ishii, Shouta M M Nakayama, Andrew Kataba, Yoshinori Ikenaka, Keisuke Saito, Yukiko Watanabe, Yoshiki Makino, Takehisa Matsukawa, Ayano Kubota, Kazuhito Yokoyama, Hazuki Mizukawa, Takafumi Hirata, Mayumi Ishizuka

  Chemosphere 212 994 - 1001 2018年12月 [査読有り][通常論文]
   

  Lead (Pb) poisoning in raptors and water birds is a serious problem in many countries. However, only a small fraction of Pb poisoning has been detected in birds. Bone specimens may be useful indices of Pb exposure because bones contain ∼90% of the total Pb body burden. The original purpose of this study was to comprehensively analyze Pb accumulation in various bone types using inductively coupled plasma-mass spectrometry (ICP-MS). Since our results showed that Pb accumulation differed greatly depending on bone type, a secondary objective was defined, aiming to investigate the fine Pb distribution and its relation to bone structure and bone marrow by using laser ablation (LA)-ICP-MS. Our findings suggested that bone samples (1) consisting of trabecular tissue and (2) those that contain bone marrow could accumulate high levels of Pb following acute exposure. The shorter turnover time of trabecular bone can cause a rapid accumulation of Pb, and bone marrow may have an important role for internal exposure of Pb to bone tissue. Pb is accumulated in bones via blood flow, and bone marrow receives blood from outside the bones. In conclusion, bone samples provide valuable information on Pb exposure and could be useful to investigate and understand mortalities related to suspected Pb poisoning.
• Comparison of xenobiotic metabolism in phase I oxidation and phase II conjugation between rats and bird species.

  Aksorn Saengtienchai, Yoshinori Ikenaka, Minami Kawata, Yusuke Kawai, Kazuki Takeda, Takamitsu Kondo, Nesta Bortey-Sam, Shouta M M Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 214 28 - 35 2018年12月 [査読有り][通常論文]
   

  There have been many reports regarding toxic chemicals in birds. Chemicals are mainly metabolized in the liver through phase I oxidation by cytochrome P450 (CYP) and phase II conjugation by conjugated enzymes, such as UDP-glucuronosyltransferase (UGT), sulfotransferase (SULT), glutathione-S-transferase (GST), etc. Xenobiotic metabolism differs among bird species, but little detailed information is available. In the present study, the four-ring polycyclic aromatic hydrocarbon (PAH), pyrene, was used as a model xenobiotic to clarify the characteristics of xenobiotic metabolism in birds compared with laboratory animals by in vivo and in vitro studies. Plasma, bile, and excreta (urine and feces) were collected after oral administration of pyrene and analyzed to clarify xenobiotic metabolism ability in chickens and quails. Interestingly, pyrenediol-glucuronide sulfate (PYDOGS) and pyrenediol-diglucuronide (PYDOGG) were present in chickens and quails but not in rats. In addition, the area under the curve (AUC), maximum plasma concentration (Cmax), and time to maximum plasma concentration (Tmax) of pyrene-1-sulfate (PYOS) were higher than those of the parent molecule, pyrene, while the elimination half-life (t1/2) and mean residence time (MRT) were faster than those of the parent pyrene. With regard to sulfation of 1-hydroxypyrene (PYOH), the maximum velocity (Vmax) and Michaelis constant (Km) of rat liver cytosol were greater than those of chicken and quail liver cytosol. Furthermore, Vmax/Km of UGT activity in rat liver microsomes was also greater than those of chicken and quail liver microsomes. Characterization of xenobiotic metabolism revealed species differences between birds and mammals, raising concerns about exposure to various xenobiotics in the environment.
• First report on OH-PAHs in South African Clarias gariepinus bile from an urban impacted system

  W. Pheiffer, N. Bortey-Sam, Y. Ikenaka, S. M.M. Nakayama, H. Mizukawa, M. Ishizuka, N. J. Smit, R. Pieters

  African Journal of Aquatic Science 43 3 305 - 312 2018年09月25日 

  The concentrations of selected hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) were determined in the bile of the African sharptooth catfish Clarias gariepinus from impoundments in the urban impacted Klip River system in Soweto, South Africa. Fish were sampled from three impoundments (Lenasia, Fleurhof, and Orlando dams) during the early high-flow season (September/October) of 2013. Biliary OH-PAHs were analysed using a high-pressure liquid chromatograph coupled to a tandem mass spectrometer (HPLC-MS/MS). Seven of the thirteen targeted metabolites were present in the fish of Soweto. The ΣOH-PAHs ranged between 0.1 and 1 876 ng ml−1, with greatest ΣOH-PAH mean at Orlando (947 ng ml−1) followed by Fleurhof (371 ng ml−1). The most dominant metabolite in the sampling area was 2–,3–OH fluorene, ranging between not detected and 1 429 ng ml−1, with the greatest mean at Orlando (709 ng ml−1). PAH metabolites quantified in C. gariepinus most likely originated from the sediments. The hepatosomatic index of the C. gariepinus increased proportionally with the biliary OH-PAH concentrations. To the authors’ knowledge this data on biliary OH-PAH for fish is the first for South Africa.
• Characterization, Spatial Variation and Risk Assessment of Heavy Metals and a Metalloid in Surface Soils in Obuasi, Ghana.

  Osei Akoto, Nesta Bortey-Sam, Shouta M M Nakayama, Yoshinori Ikenaka, Elvis Baidoo, Joseph Apau, Jemima Tiwaa Marfo, Mayumi Ishizuka

  Journal of health & pollution 8 19 180902 - 180902 2018年09月 [査読有り][通常論文]
   

  Background: Soil contamination with heavy metals and metalloids has become an increasingly important issue in recent years. Objectives: The present study examines possible contamination of the environment with metals from gold mining activities in Obuasi, Ghana. Methods: Soil samples were collected from commercial and residential areas and tailing dams in Obuasi in order to investigate the extent of lead (Pb), cadmium (Cd), mercury (Hg), copper (Cu), zinc (Zn), cobalt (Co), chromium (Cr), nickel (Ni) and arsenic (As) pollution, create thematic maps showing the extent of heavy metals pollution, identify the sources of pollution, and to assess risks to humans and the surrounding ecological system. Results: Mean concentrations of metals from the study were found in the order of As > Cu > Zn > Cr > Ni > Pb > Co > Hg > Cd. The results showed that all communities were severely polluted with As, and distribution maps highlighted two hot spots at the sulfite treatment plant and Pompura treatment plant tailings dams. Additionally, the levels of Pb, Cu and Zn were elevated around the city center where vehicular traffic is very dense. Principal component analysis indicated that mining activities may have significantly contributed to metal levels in Obuasi soils. The potential ecological risk (RI) indicated that soils in 41% of the communities pose very high risks to the surrounding ecological system, 50% pose considerable risk, and 9% pose a moderate risk. Arsenic and Hg contributed 73 and 15% of the RI, respectively. The average hazard quotient due to soil As exposure was 2.51 ± 1.23 and ingestion of soils in 95% of the communities in the study area could pose non-carcinogenic health risks to children. Moreover, the average cancer risk for children from the communities was 1.13 × 10-3. Based on the United States Environmental Protection Agency (USEPA) recommendation for cancer risk of 10-6 to 10-4, the cancer risk for children (> 10-3) was higher in 45% of the studied communities. Conclusions: The central part of the study area is polluted with Pb, Zn and Cu, and As pollution is severe in all of the studied communities. The RI from all study sites revealed very high risk to the ecological system, including mammals. There could be non-cancer and cancer risks to Obuasi residents due to ingestion of As-contaminated soils, and children are particularly vulnerable. Competing Interests: The author declares no competing financial interests.
• Lead and cadmium excretion in feces and urine of children from polluted townships near a lead-zinc mine in Kabwe, Zambia.

  John Yabe, Shouta M M Nakayama, Yoshinori Ikenaka, Yared B Yohannes, Nesta Bortey-Sam, Abel Nketani Kabalo, John Ntapisha, Hazuki Mizukawa, Takashi Umemura, Mayumi Ishizuka

  Chemosphere 202 48 - 55 2018年07月 [査読有り][通常論文]
   

  Lead (Pb) and cadmium (Cd) are toxic metals that exist ubiquitously in the environment. Children in polluted areas are particularly vulnerable to metal exposure, where clinical signs and symptoms could be nonspecific. Absorbed metals are excreted primarily in urine and reflect exposure from all sources. We analyzed Pb and Cd concentrations in blood, feces and urine of children from polluted townships near a lead-zinc mine in Kabwe, Zambia, to determine concurrent childhood exposure to the metals. Moreover, the study determined the Pb and Cd relationships among urine, feces and blood as well as accessed the potential of urine and fecal analysis for biomonitoring of Pb and Cd exposure in children. Fecal Pb (up to 2252 mg/kg, dry weight) and urine Pb (up to 2914 μg/L) were extremely high. Concentrations of Cd in blood (Cd-B) of up to 7.7 μg/L, fecal (up to 4.49 mg/kg, dry weight) and urine (up to 18.1 μg/L) samples were elevated. metal levels were higher in younger children (0-3 years old) than older children (4-7). Positive correlations were recorded for Pb and Cd among blood, urine and fecal samples whereas negative correlations were recorded with age. These findings indicate children are exposed to both metals at their current home environment. Moreover, urine and feces could be useful for biomonitoring of metals due to their strong relationships with blood levels. There is need to conduct a clinical evaluation of the affected children to fully appreciate the health impact of these metal exposure.
• Investigation of hepatic warfarin metabolism activity in rodenticide-resistant black rats (Rattus rattus) in Tokyo by in situ liver perfusion.

  Kazuki Takeda, Yoshinori Ikenaka, Kazuyuki D Tanaka, Shouta M M Nakayama, Tsutomu Tanikawa, Hazuki Mizukawa, Mayumi Ishizuka

  Pesticide biochemistry and physiology 148 42 - 49 2018年06月 [査読有り][通常論文]
   

  Anti-blood coagulation rodenticides, such as warfarin, have been used all over the world. They inhibit vitamin K epoxide reductase (VKOR), which is necessary for producing several blood clotting factors. This inhibition by rodenticides results in lethal hemorrhage in rodents. However, heavy usage of these agents has led to the appearance of rodenticide-resistant rats. There are two major mechanisms underlying this resistance, i.e., mutation of the target enzyme of warfarin, VKOR, and enhanced metabolism of warfarin. However, there have been few studies regarding the hepatic metabolism of warfarin, which should be related to resistance. To investigate warfarin metabolism in resistant rats, in situ liver perfusion of warfarin was performed with resistant black rats (Rattus rattus) from Tokyo, Japan. Liver perfusion is an in situ methodology that can reveal hepatic function specifically with natural composition of the liver. The results indicated enhanced hepatic warfarin hydroxylation activity compared with sensitive black rats. On the other hand, in an in vitro microsomal warfarin metabolism assay to investigate kinetic parameters of cytochrome P450, which plays a major role in warfarin hydroxylation, the Vmax of resistant rats was slightly but significantly higher compared to the results obtained in the in situ study. These results indicated that another factor like electron donators may also contribute to the enhanced metabolism in addition to high expression of cytochrome P450.
• A glycomics approach to discover novel renal biomarkers in birds by administration of cisplatin and diclofenac to chickens

  C. Ishii, Y. Ikenaka, O. Ichii, S. M.M. Nakayama, S. I. Nishimura, T. Ohashi, M. Tanaka, H. Mizukawa, M. Ishizuka

  Poultry Science 97 5 1722 - 1729 2018年05月 

  Avian species have a unique renal structure and abundant blood flow into the kidneys. Although many birds die due to nephrotoxicity caused by chemicals, there are no early biomarkers for renal lesions. Uric acid level in blood, which is generally used as a renal biomarker, is altered when the kidney function is damaged by over 70%. Therefore, early biomarkers for kidney injury in birds are needed. In humans, glycomics has been at the forefront of biological and medical sciences, and glycans are used as biomarkers of diseases, such as carcinoma. In this study, a glycomics approach was used to screen for renal biomarkers in chicken. First, a chicken model of kidney damage was generated by injection of diclofenac or cisplatin, which cause acute interstitial nephritis (AIN) and acute tubular necrosis (ATN), respectively. The nephrotoxicity levels were determined by a blood chemical test and histopathological analysis. The plasma N-glycans were then analyzed to discover renal biomarkers in birds. Levels of 14 glycans increased between pre- and post administration in kidney-damaged chickens in the diclofenac group, and some of these glycans had the same presumptive composition as those in human renal carcinoma patients. Glycan levels did not change remarkably in the cisplatin group. It is possible that there are changes in glycan expression due to AIN, but they do not reflect ATN. Although further research is needed in other species of birds, glycans are potentially useful biomarkers for AIN in avian species.
• Human Health Risk from Consumption of Marine Fish Contaminated with DDT and Its Metabolites in Maputo Bay, Mozambique.

  L A Thompson, Y Ikenaka, Y B Yohannes, T Ichise, G Ito, N Bortey-Sam, J J van Vuren, V Wepener, N J Smit, W S Darwish, S M M Nakayama, H Mizukawa, M Ishizuka

  Bulletin of environmental contamination and toxicology 100 5 672 - 676 2018年05月 

  Many countries with incidence of malaria, including those surrounding Maputo Bay, use dichloro-diphenyl-trichloroethane (DDT) to reduce mosquitoes. This study is the first to estimate the human health risk associated with consumption of marine fish from Maputo Bay contaminated with DDTs. The median for ∑DDTs was 3.8 ng/g ww (maximum 280.9 ng/g ww). The overall hazard ratio for samples was 1.5 at the 75th percentile concentration and 28.2 at the 95th percentile. These calculations show increased potential cancer risks due to contamination by DDTs, data which will help policy makers perform a risk-benefit analysis of DDT use in malaria control programs in the region.
• Accumulation patterns and risk assessment of metals and metalloid in muscle and offal of free-range chickens, cattle and goat in Benin City, Nigeria.

  Emmanuel Temiotan Ogbomida, Shouta M M Nakayama, Nesta Bortey-Sam, Balazs Oroszlany, Isioma Tongo, Alex Ajeh Enuneku, Ogbeide Ozekeke, Martins Oshioriamhe Ainerua, Iriagbonse Priscillia Fasipe, Lawrence Ikechukwu Ezemonye, Hazuki Mizukawa, Yoshinori Ikenaka, Mayumi Ishizuka

  Ecotoxicology and environmental safety 151 98 - 108 2018年04月30日 [査読有り][通常論文]
   

  The use of free range animals for monitoring environmental health offers opportunities to detect exposure and assess the toxicological effects of pollutants in terrestrial ecosystems. Potential human health risk of dietary intake of metals and metalloid via consumption of offal and muscle of free range chicken, cattle and goats by the urban population in Benin City was evaluated. Muscle, gizzard, liver and kidney samples were analyzed for Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Cd, and Pb concentrations using inductively coupled plasma mass spectrometer (ICP-MS) while Hg was determined using Hg analyzer. Mean concentrations of metals (mg/kg ww) varied significantly depending upon the tissues and animal species. Human health risk estimations for children and adults showed estimated daily intake (EDI) values of tissues below oral reference dose (RfD) threshold for non essential metals Cd, As, Pb and Hg thus strongly indicating no possible health risk via consumption of animal based food. Calculated Hazard quotient (THQ) was less than 1 (< 1) for all the metals analyzed for both adult and children. However, Cd and As had the highest value of THQ suggestive of possible health risk associated with continuous consumption of Cd and As contaminated animal based foods. Hazard Index (HI) for additive effect of metals was higher in chicken liver and gizzard for children and chicken liver for adults. Thus, HI indicated that chicken liver and gizzard may contribute significantly to adult and children dietary exposure to heavy metals. Principal component analysis (PCA) showed a clear species difference in metal accumulation between chickens and the ruminants. This study provides baseline data for future studies and also valuable evidence of anthropogenic impacts necessary to initiate national and international policies for control of heavy metal and metalloid content in food items.
• Association between human exposure to heavy metals/metalloid and occurrences of respiratory diseases, lipid peroxidation and DNA damage in Kumasi, Ghana.

  Nesta Bortey-Sam, Yoshinori Ikenaka, Osei Akoto, Shouta M M Nakayama, Kwadwo A Asante, Elvis Baidoo, Christian Obirikorang, Hazuki Mizukawa, Mayumi Ishizuka

  Environmental pollution (Barking, Essex : 1987) 235 163 - 170 2018年04月 [査読有り][通常論文]
   

  Heavy metals and metalloids contamination in soils, water, food and livers of wild rats have been studied in Kumasi, Ghana and despite the estimated risks to residents, there is no epidemiological study to ascertain these projections. In addition, the World Health Organization and International Agency for Research on Cancer have reported an increase in respiratory diseases and cancers, in Ghana. The study's purpose was therefore to explore the potential associations between metal exposure and occurrences of respiratory diseases, lipid peroxidation and/or DNA damage to different age groups and sexes in Kumasi. Human urine was collected from the general population in urban and control sites in Kumasi and nine metals were measured in each sample. Results showed that although Zn was the most abundant total urinary As concentration was higher in 83% of samples compared to reference values. Urinary concentrations of metals, malondialdehyde (MDA) and 8-hydroxy-2-deoxy-guanosine (8-OHdG) were higher in urban sites compared to the control site. Based on the results obtained, there was no significant correlation between urinary metals and age. However, urinary Cd and MDA were highest in age groups 61-85 and 3-20 years, respectively. Significantly higher levels of urinary Co, As and Cd were detected in female participants. The study revealed that exposure to As was significantly associated with increased odds of asthma (odds ratio (OR) = 2.76; CI: 1.11-6.83) and tachycardia (OR = 3.93; CI: 1.01-15.4). Significant association was observed between urinary metals and MDA and 8-OHdG indicating possibility of lipid peroxidation and/or DNA damage in Kumasi residents.
• Sex and site differences in urinary excretion of conjugated pyrene metabolites in the West African Shorthorn cattle.

  Nesta Bortey-Sam, Yoshinori Ikenaka, Osei Akoto, Shouta M M Nakayama, Jemima T Marfo, Aksorn Saengtienchai, Hazuki Mizukawa, Mayumi Ishizuka

  The Journal of veterinary medical science 80 2 375 - 381 2018年03月02日 [査読有り][通常論文]
   

  Industrialization, economic and population growth rates in Ghana have increased the release of contaminants including polycyclic aromatic hydrocarbons (PAHs) into the environment through which humans and animals are exposed. Cattle is reported to be exposed to high levels of PAHs through feed and inhalation. Once exposed, PAHs are metabolized and excreted in urine, feces or bile. In a previous study, cattle in Ghana was reported to excrete high levels of 1-hydroxypyrene (1-OHPyr) due to high exposure to the parent compound, pyrene. 1-OHPyr is further metabolized to glucuronide and sulfate conjugates. Thus, the aim of this study was to investigate the sex and site differences in urinary excretion of conjugated pyrene metabolites using cattle urine collected from rural and urban sites of the Ashanti region, Ghana. From the results, geometric mean concentration adjusted by specific gravity indicated that 1-OHPyreneGlucuronide (PyG) was the most abundant conjugate followed by PyrenediolSulfate (M3). The sum of conjugated pyrene metabolites and sum of both conjugated and deconjugated pyrene metabolites correlated significantly with PyG, PydiolSulfate (M2) and PydiolSulfate (M3). The study revealed no significant difference in urinary excretion of conjugated pyrene metabolites between rural and urban sites. This indicated that similar to urban sites, cattle in rural sites were exposed to high levels of pyrene. There was no significant difference in urinary concentrations of conjugated pyrene metabolites between sexes.
• β-carotene and retinol reduce benzo[a]pyrene-induced mutagenicity and oxidative stress via transcriptional modulation of xenobiotic metabolizing enzymes in human HepG2 cell line.

  Darwish WS, Ikenaka Y, Nakayama S, Mizukawa H, Thompson LA, Ishizuka M

  Environmental science and pollution research international 25 7 6320 - 6328 2018年03月 [査読有り][通常論文]
   

  Benzo[a]pyrene (B[a]P) is one of the polycyclic aromatic hydrocarbons which is formed due to smoking of foods, incomplete combustion of woods, vehicle exhausts, and cigarettes smokes. B[a]P gets entry into human and animal bodies mainly through their diets. Metabolic activation of B[a]P is required to induce mutagenesis and carcinogenesis in animal and human studies. Carotenoids and retinoids are phytochemicals that if ingested have multiple physiological interferences in the human and animal bodies. In this study, we firstly investigated the protective effects of β-carotene, β-apo-8-carotenal, retinol, and retinoic acid against B[a]P-induced mutagenicity and oxidative stress in human HepG2 cells. Secondly, we tested the hypothesis of modulating xenobiotic metabolizing enzymes (XMEs) by carotenoids and retinoids as a possible mechanism of protection by these micronutrients against B[a]P adverse effects. The obtained results declared that β-carotene and retinol significantly reduced B[a]P-induced mutagenicity and oxidative stress. Tested carotenoids and retinoids reduced B[a]P-induced phase I XMEs and induced B[a]P reduced phase II and III XMEs. Thus, the protective effects of these micronutrients are probably due to their ability of induction of phase II and III enzymes and interference with the induction of phase I enzymes by the promutagen, B[a]P. It is highly recommended to consume foods rich in these micronutrients in the areas of high PAH pollution.
• Contamination by neonicotinoid insecticides and their metabolites in Sri Lankan black tea leaves and Japanese green tea leaves.

  Yoshinori Ikenaka, Kazutoshi Fujioka, Tomonori Kawakami, Takahiro Ichise, Nesta Bortey-Sam, Shouta M M Nakayama, Hazuki Mizukawa, Kumiko Taira, Keisuke Takahashi, Keisuke Kato, Koji Arizono, Mayumi Ishizuka

  Toxicology reports 5 744 - 749 2018年 [査読有り][通常論文]
   

  Tea is one of the world's most popular beverages due to health promoting effects. Despite these, there have been concerns about the adverse effects of tea contamination by neonicotinoid insecticides. Only a handful of studies on neonicotinoid insecticides in tea have been carried out and this study was therefore performed to determine the concentrations of seven neonicotinoid insecticides and 20 metabolites in Japanese green tea leaves, and black tea leaves from Sri Lanka; and assess the Maximum Daily Intake (MDI) of neonicotinoid insecticides. From the results, the seven parent compounds were detected in Japanese tea leaves and beverages. Dinotefuran (3004 ng/g) was found at the highest level in green tea leaves. Ten of the 20 metabolites were detected in Japanese tea products. Dinotefuran-urea (92%) and thiacloprid-amide (89%) were most frequently detected in Japanese tea leaves. Clothianidin-urea (100 ng/g) was found at the highest level in green tea leaves. Neonicotinoid insecticides and metabolites were not detected in Sri Lankan black tea leaves. The concentrations and MDI of neonicotinoid insecticides in tea leaves were below the Maximum Residual Levels (MRLs) and Acceptable Daily Intakes (ADIs), respectively.
• Investigation of mRNA expression changes associated with field exposure to DDTs in chickens from KwaZulu-Natal, South Africa.

  Lesa A Thompson, Yoshinori Ikenaka, Wageh S Darwish, Yared B Yohannes, Johan J van Vuren, Victor Wepener, Nico J Smit, Atnafu G Assefa, Ahmed Tharwat, Walaa Fathy Saad Eldin, Shouta M M Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  PloS one 13 10 e0204400  2018年 [査読有り][通常論文]
   

  The objective of this study was to identify potential mRNA expression changes in chicken livers associated with environmental exposure to dichloro-diphenyl-trichloroethane (DDT) and its metabolites (DDTs). In particular, we focused on genes relating to the immune system and metabolism. We analyzed liver samples from free-ranging chickens in KwaZulu-Natal, South Africa, for contamination by DDTs. This area predominantly uses DDT in its malaria control program, and homes are sprayed annually with the pesticide. Genes relating to the immune system and metabolism were selected as potential genetic biomarkers that could be linked to higher contamination with DDTs. RT-qPCR analysis on 39 samples showed strong correlations between DDTs contamination and mRNA expression for the following genes: AvBD1, AvBD2, AvBD6 and AvBD7 (down-regulated), and CYP17, ELOVL2 and SQLE (up-regulated). This study shows for the first time interesting and significant correlations between genetic material collected from environmentally-exposed chickens and mRNA expression of several genes involved in immunity and metabolism. These findings show the usefulness of analysis on field samples from a region with high levels of environmental contamination in detecting potential biomarkers of exposure. In particular, we observed clear effects from DDT contamination on mRNA expression of genes involved in immune suppression, endocrine-disrupting effects, and lipid dysregulation. These results are of interest in guiding future studies to further elucidate the pathways involved in and clinical importance of toxicity associated with DDT exposure from contaminated environments, to ascertain the health risk to livestock and any subsequent risks to food security for people.
• Concentrations and human health risk assessment of DDT and its metabolites in free-range and commercial chicken products from KwaZulu-Natal, South Africa

  L. A. Thompson, Y. Ikenaka, Y. B. Yohannes, J. J. van Vuren, V. Wepener, N. J. Smit, W. S. Darwish, S. M. M. Nakayama, H. Mizukawa, M. Ishizuka

  Food Additives & Contaminants: Part A 34 11 1959 - 1969 2017年11月02日
• Lead exposure in raptors from Japan and source identification using Pb stable isotope ratios.

  Chihiro Ishii, Shouta M M Nakayama, Yoshinori Ikenaka, Hokuto Nakata, Keisuke Saito, Yukiko Watanabe, Hazuki Mizukawa, Shinsuke Tanabe, Kei Nomiyama, Terutake Hayashi, Mayumi Ishizuka

  Chemosphere 186 367 - 373 2017年11月 [査読有り][通常論文]
   

  Lead (Pb) poisoning is widespread among raptors and water birds. In Japan, fragments of Pb ammunition are still found in endangered eagles although more than 10 years have passed since legislation regarding use of Pb ammunition was introduced. This study was performed to investigate Pb exposure in raptors from various locations in Japan. We measured hepatic and renal Pb concentrations and hepatic Pb isotope ratios of Steller's sea eagles (Haliaeetus pelagicus), white-tailed sea eagles (Haliaeetus albicilla), golden eagles (Aquila chrysaetos), and 13 other species (total 177 individuals) that were found dead, as well as blood samples from three eagles found in a weakened state during 1993-2015 from Hokkaido (northern part), Honshu (the main island), and Shikoku (a southern island) of Japan. In the present study in Hokkaido, one quarter of the sea eagles showed a high Pb concentration, suggesting exposure to abnormally high Pb levels and Pb poisoning. Pb isotope ratios indicated that endangered Steller's sea eagle and white-tailed sea eagle were poisoned by Pb ammunition that was used illegally in Hokkaido. In other areas of Japan, both surveillance and regulations were less extensive than in Hokkaido, but Pb poisoning in raptors was also noted. Therefore, Pb poisoning is still a serious problem in raptors in various areas of Japan due to accidental ingestion of materials containing Pb, especially Pb ammunition.
• Anthropogenic and Naturally Produced Brominated Phenols in Pet Blood and Pet Food in Japan.

  Hazuki Mizukawa, Kei Nomiyama, Susumu Nakatsu, Miyuki Yamamoto, Mayumi Ishizuka, Yoshinori Ikenaka, Shouta M M Nakayama, Shinsuke Tanabe

  Environmental science & technology 51 19 11354 - 11362 2017年10月03日 [査読有り][通常論文]
   

  Present study determined concentrations and residue patterns of bromophenols (BPhs) in whole blood samples of pet cats and pet dogs collected from veterinary hospitals in Japan. BPhs concentrations were higher in cat blood than in dog blood, with statistically insignificant differences (p = 0.07). Among the congeners, 2,4,6-tribromophenol (TBPh) constituted the majority of BPhs (>90%) detected in both species. Analysis of commercial pet food to estimate exposure routes showed that the most abundant congener in all pet food samples was 2,4,6-TBPh, accounting for >99% of total BPhs. This profile is quite similar to the blood samples of the pets, suggesting that diet might be an important exposure route for BPhs in pets. After incubation in polybrominated diphenyl ether (PBDE) mixtures (BDE-47, BDE-99 and BDE-209), 2,4,5-TBPh was found in dog liver microsomes but not in cat liver microsomes, implying species-specific metabolic capacities for PBDEs. Formation of 2,4,5-TBPh occurred by hydroxylation at the 1' carbon atom of the ether bond of BDE-99 is similar to human study reported previously. Hydroxylated PBDEs were not detected in cats or dogs; therefore, diphenyl ether bond cleavage of PBDEs can also be an important metabolic pathway for BPhs formation in cats and dogs.
• Assessment of DDT contamination in house rat as a possible bioindicator in DDT-sprayed areas from Ethiopia and South Africa.

  Yared Beyene Yohannes, Yoshinori Ikenaka, Gengo Ito, Shouta M M Nakayama, Hazuki Mizukawa, Victor Wepener, Nico J Smit, Johan H J Van Vuren, Mayumi Ishizuka

  Environmental science and pollution research international 24 30 23763 - 23770 2017年10月 [査読有り][通常論文]
   

  Ethiopia and South Africa are among the few countries to still implement indoor residual spraying with dichloro-diphenyl-trichloroethane (DDT) for malaria vector control. In this study, we investigated the levels and ecological risks of DDT and its metabolites in liver tissues of house rat, as a sentinel animal, for providing an early warning system for public health and wildlife intervention from Ethiopia and South Africa. The results showed that ΣDDT concentration ranged from 127 to 9155 μg/kg wet weight, and the distribution order of DDT and its metabolites in the analyzed liver samples was p,p'-DDD > p,p'-DDE > p,p'-DDT, o,p'-DDT, and o,p'-DDD. The risk assessment indicated a potential adverse impact on humans, especially for pregnant women and children, because they spend majority of their time in a DDT-sprayed house. The ecological assessment also showed a concern for birds of prey and amphibians like frogs. This study is the first report on DDT contamination in liver tissues of house rats from Ethiopia and South Africa, and henceforth, the data will serve as a reference data for future studies.
• Oxidative stress and respiratory symptoms due to human exposure to polycyclic aromatic hydrocarbons (PAHs) in Kumasi, Ghana.

  Nesta Bortey-Sam, Yoshinori Ikenaka, Osei Akoto, Shouta M M Nakayama, Kwadwo A Asante, Elvis Baidoo, Christian Obirikorang, Aksorn Saengtienchai, Norikazu Isoda, Collins Nimako, Hazuki Mizukawa, Mayumi Ishizuka

  Environmental pollution (Barking, Essex : 1987) 228 311 - 320 2017年09月 [査読有り][通常論文]
   

  Studies of polycyclic aromatic hydrocarbons (PAHs) and its metabolites in PM10, soils, rat livers and cattle urine in Kumasi, Ghana, revealed high concentrations and cancer potency. In addition, WHO and IARC have reported an increase in cancer incidence and respiratory diseases in Ghana. Human urine were therefore collected from urban and control sites to: assess the health effects associated with PAHs exposure using malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OHdG); identify any association between OH-PAHs, MDA, 8-OHdG with age and sex; and determine the relationship between PAHs exposure and occurrence of respiratory diseases. From the results, urinary concentrations of the sum of OH-PAHs (∑OHPAHs) were significantly higher from urban sites compared to the control site. Geometric mean concentrations adjusted by specific gravity, GMSG, indicated 2-OHNaphthalene (2-OHNap) (6.01 ± 4.21 ng/mL) as the most abundant OH-PAH, and exposure could be through the use of naphthalene-containing-mothballs in drinking water purification, insect repellent, freshener in clothes and/or "treatment of various ailments". The study revealed that exposure to naphthalene significantly increases the occurrence of persistent cough (OR = 2.68, CI: 1.43-5.05), persistent headache (OR = 1.82, CI: 1.02-3.26), tachycardia (OR = 3.36, CI: 1.39-8.10) and dyspnea (OR = 3.07, CI: 1.27-7.43) in Kumasi residents. Highest level of urinary 2-OHNap (224 ng/mL) was detected in a female, who reported symptoms of persistent cough, headache, tachycardia, nasal congestion and inflammation, all of which are symptoms of naphthalene exposure according to USEPA. The ∑OHPAHs, 2-OHNap, 2-3-OHFluorenes, and -OHPhenanthrenes showed a significantly positive correlation with MDA and 4-OHPhenanthrene with 8-OHdG, indicating possible lipid peroxidation/cell damage or degenerative disease in some participants. MDA and 8-OHdG were highest in age group 21-60. The present study showed a significant sex difference with higher levels of urinary OH-PAHs in females than males.
• Contamination Levels and Sources of Heavy Metals and a Metalloid in Surface Soils in the Kumasi Metropolis, Ghana.

  Osei Akoto, Nesta Bortey-Sam, Yoshinori Ikenaka, Shouta M M Nakayama, Elvis Baidoo, Yared Beyene Yohannes, Mayumi Ishizuka

  Journal of health & pollution 7 15 28 - 39 2017年09月 [査読有り][通常論文]
   

  Background: Environmental contamination with heavy metals and metalloids due to industrial, smelting and mining activities have become common in large and growing cities. Kumasi is one of the most industrialized cities in Ghana and experiences metal pollution due to recent and past activities. Although metals are naturally abundant in the area, their accumulation in soils could potentially lead to adverse effects on local ecosystems. Objectives: The aims of this study were to determine the distribution, enrichment, geoaccumulation and sources of metals in Kumasi soils and to estimate the contamination factor (CF) and pollution load index (PLI) of these metals in soils. Methods: Concentrations of eight heavy metals and a metalloid were determined in 112 soil samples randomly collected from 31 sampling sites in the area. In addition, 5 soil samples were collected from a pristine site (Kwame Nkrumah University of Science and Technology Botanical Gardens) for data comparison, to determine the local background values for metal concentrations and to evaluate the extent of metal pollution in the study area. Results: Heavy metals such as zinc (Zn), lead (Pb), cadmium (Cd) and chromium (Cr) were enriched in 65, 32, 58 and 93% of the sampling sites, respectively, and geo-accumulation indexes for Cr, Zn, Cd, mercury (Hg) and Pb showed moderate to extreme contamination in 100, 97, 77, 65 and 45% of the sampling sites, respectively. Principal component and cluster analyses revealed that industrial activities including mining were the major sources of metals in Kumasi soils with high metal input in the community of Suame. Distribution maps revealed hotspots of Cd, nickel (Ni), arsenic (As), cobalt (Co), copper (Cu) and Pb in Suame. The highest CFs for Cu, Cd, Ni, As, Co and Pb highlighted anthropogenic inputs in Suame, while Hg was highest in Mbrom, Zn in Suntreso, and Cr in Aboabo. Conclusions: The PLI of metals revealed Suame as the most polluted study site, while Anomangye and Bomso were the least polluted.
• Sediment Metal Contamination in the Kafue River of Zambia and Ecological Risk Assessment.

  Ethel M'kandawire, Kennedy Choongo, John Yabe, Maxwell Mwase, Ngonda Saasa, Shouta M M Nakayama, Nesta Bortey-Sam, Claudia A Blindauer

  Bulletin of environmental contamination and toxicology 99 1 108 - 116 2017年07月 [査読有り][通常論文]
   

  Zambia's Kafue River receives wastes from various sources, resulting in metal pollution. This study determined the degree of contamination of 13 metals (Al, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Cd, Hg and Pb) in Kafue River sediment and the associated ecological risks at six sites in three different seasons. The level of contamination for most metals showed significant site and seasonal differences. The contamination factor and pollution load index indicated that concentrations of most metals particularly copper (Cu), cobalt (Co), manganese (Mn) and arsenic (As) were very high at sites within the Copperbelt mining area. The geoaccumulation index showed an absence of anthropogenic enrichment with Cd and Hg at all the study sites and extreme anthropogenic enrichment with Cu at sites in the Copperbelt mining area. Potential ecological risk showed that Cu and As were likely to cause adverse biological effects to aquatic organisms in the Copperbelt mining region of the Kafue River.
• Uridine Diphosphate-Glucuronosyltransferase (UGT) 2B Subfamily Interspecies Differences in Carnivores.

  Takamitsu Kondo, Yoshinori Ikenaka, Shouta M M Nakayama, Yusuke K Kawai, Hazuki Mizukawa, Yoko Mitani, Kei Nomiyama, Shinsuke Tanabe, Mayumi Ishizuka

  Toxicological sciences : an official journal of the Society of Toxicology 158 1 90 - 100 2017年07月01日 [査読有り][通常論文]
   

  UDP-glucuronosyltransferases (UGTs) are among the most important xenobiotic metabolizing enzymes that conjugate a wide range of chemicals. Previous studies showed that Felidae and Pinnipedia species have very low UGT activities toward some phenolic compounds because of the UGT1A6 pseudogene and small numbers of UGT1A isozymes. In addition to the UGT1As, UGT2Bs isozymes also conjugate various endogenous (eg, estrogens, androgens, and bile acids) and exogenous compounds (opioids, non-steroidal anti-inflammatory drugs, and environmental pollutants). However UGT2B activity and genetic background are unknown in carnivore species. Therefore, this study was performed to elucidate the species differences of UGT2Bs. Using typical substrates for UGT2Bs, UGT activity was measured in vitro. In addition, UGT2B genetic features are analyzed in silico. Results of UGT activity measurement indicate marked species differences between dogs and other carnivores (cats, Northern fur seals, Steller sea lions, Harbor seals, and Caspian seals). Dogs have very high Vmax/Km toward estradiol (17-glucuronide), estrone, lorazepam, oxazepam, and temazepam. Conversely, cats and pinniped species (especially Caspian seals and Harbor seals) have very low activities toward these substrates. The results of genetic synteny analysis indicate that Felidae and pinniped species have very small numbers of UGT2B isozymes (one or none) compared with dogs, rodents, and humans. Furthermore, Felidae species have the same nonsense mutation in UGT2B, which suggests that Felidae UGT2B31-like is also a pseudogene in addition to UGT1A6. These findings of lower activity of UGT2B suggest that Felidae and some pinniped species have very low UGT activity toward a wide range of chemicals. These results are important for Felidae and Pinnipedia species that are frequently exposed to drugs and environmental pollutants.
• Contamination status and accumulation characteristics of heavy metals and arsenic in five seabird species from the central Bering Sea.

  Chihiro Ishii, Yoshinori Ikenaka, Shouta M M Nakayama, Hazuki Mizukawa, Yared Beyene Yohannes, Yutaka Watanuki, Masaaki Fukuwaka, Mayumi Ishizuka

  The Journal of veterinary medical science 79 4 807 - 814 2017年04月20日 [査読有り][通常論文]
   

  Seabirds are marine top predators and accumulate high levels of metals and metalloids in their tissues. Contamination by metals in the highly productive offshore region has become a matter of public concern. It is home to 80% of the seabird population in the U.S.A., 95% of northern fur seals (Callorhinus ursinus), and major populations of Steller sea lions (Eumetopias jubatus), walruses (Odobenus rosmarus) and whales. Here, the concentrations of eight heavy metals (Hg, Cd, Cr, Co, Ni, Cu, Zn and Pb) and a metalloid (As) in the liver and kidneys of the northern fulmar (Fulmarus glacialis), thick-billed murre (Uria lomvia), short-tailed shearwater (Puffinus tenuirostris), tufted puffin (Fratercula cirrhata) and horned puffin (Fratercula corniculata) collected in the Bering Sea were measured. As proxies of trophic level and habitat, nitrogen (δ15N) and carbon (δ13C) stable isotope ratios of breast muscles were also measured. Hepatic Hg concentration was high in northern fulmar, whereas Cd level was high in tufted puffin and northern fulmar. The Hg concentration and δ15N value were positively correlated across individual birds, suggesting that Hg uptake was linked to the trophic status of consumed prey. Furthermore, Hg concentration in our study was higher than those of the same species of seabirds collected in 1990.
• Organochlorine pesticide contamination of foods in Africa: incidence and public health significance.

  Lesa A Thompson, Wageh Sobhy Darwish, Yoshinori Ikenaka, Shouta M M Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  The Journal of veterinary medical science 79 4 751 - 764 2017年04月08日 [査読有り][通常論文]
   

  Organochlorine pesticides (OCPs) have been used worldwide, particularly in Africa, for several decades. Although many are banned, several African countries still use OCPs especially for the prevention and control of malaria. OCPs are characterized by their bio-accumulation in the environment, especially in the food chain, where they find their way into the human body. Despite no clear epidemiological studies confirming hazardous effects of these chemicals on human health, many studies have reported positive associations between the use of OCPs and neurological and reproductive disorders, and cancer risk. There is a clear gap in published reports on OCPs in Africa and their potential health hazards. Thus, the aim of this review is to summarize the incidence of OCP contamination in various foods in Africa, to demonstrate the potential transmission of these chemicals to people and to discuss their possible health hazards.
• Trace Element Contamination in Tissues of Four Bird Species from the Rift Valley Region, Ethiopia.

  Yared Beyene Yohannes, Yoshinori Ikenaka, Shouta M M Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  Bulletin of environmental contamination and toxicology 98 2 172 - 177 2017年02月 [査読有り][通常論文]
   

  Concentrations of ten trace elements (Hg, As, Cd, Pb, Co, Cr, Cu, Ni, Se and Zn) were determined in different tissues (liver, kidney, muscle, heart and brain) of African sacred ibis (Threskiornis aethiopicus), Hamerkop (Scopus umbretta), marabou stork (Leptoptilos crumeniferus) and great white pelican (Pelecanus onocrotalus) inhabiting the Ethiopian Rift Valley region. There were differences in trace element patterns among the bird species. Significantly (p < 0.05) higher concentrations of Cd (5.53 µg/g dw ± 2.94) in kidney and Hg (0.75 µg/g ww ± 0.30) in liver were observed in the great white pelican compared to the other species, and liver concentrations of these two elements showed positive correlations with trophic level. Concentrations of toxic elements (As, Cd, Pb and Hg) in liver were below their respective toxicological thresholds, indicating that the data may provide baseline information for future studies.
• Monitoring Lead (Pb) Pollution and Identifying Pb Pollution Sources in Japan Using Stable Pb Isotope Analysis with Kidneys of Wild Rats.

  Hokuto Nakata, Shouta M M Nakayama, Balazs Oroszlany, Yoshinori Ikenaka, Hazuki Mizukawa, Kazuyuki Tanaka, Tsunehito Harunari, Tsutomu Tanikawa, Wageh Sobhy Darwish, Yared B Yohannes, Aksorn Saengtienchai, Mayumi Ishizuka

  International journal of environmental research and public health 14 1 2017年01月10日 [査読有り][通常論文]
   

  Although Japan has been considered to have little lead (Pb) pollution in modern times, the actual pollution situation is unclear. The present study aims to investigate the extent of Pb pollution and to identify the pollution sources in Japan using stable Pb isotope analysis with kidneys of wild rats. Wild brown (Rattus norvegicus, n = 43) and black (R. rattus, n = 98) rats were trapped from various sites in Japan. Mean Pb concentrations in the kidneys of rats from Okinawa (15.58 mg/kg, dry weight), Aichi (10.83), Niigata (10.62), Fukuoka (8.09), Ibaraki (5.06), Kyoto (4.58), Osaka (4.57), Kanagawa (3.42), and Tokyo (3.40) were above the threshold (2.50) for histological kidney changes. Similarly, compared with the previous report, it was regarded that even structural and functional kidney damage as well as neurotoxicity have spread among rats in Japan. Additionally, the possibility of human exposure to a high level of Pb was assumed. In regard to stable Pb isotope analysis, distinctive values of stable Pb isotope ratios (Pb-IRs) were detected in some kidney samples with Pb levels above 5.0 mg/kg. This result indicated that composite factors are involved in Pb pollution. However, the identification of a concrete pollution source has not been accomplished due to limited differences among previously reported values of Pb isotope composition in circulating Pb products. Namely, the current study established the limit of Pb isotope analysis for source identification. Further detailed research about monitoring Pb pollution in Japan and the demonstration of a novel method to identify Pb sources are needed.
• Spatial and temporal profile of cisplatin delivery by ultrasound-assisted intravesical chemotherapy in a bladder cancer model.

  Noboru Sasaki, Kazuhiro Ishi, Nobuki Kudo, Shouta M M Nakayama, Kensuke Nakamura, Keitaro Morishita, Hiroshi Ohta, Mayumi Ishizuka, Mitsuyoshi Takiguchi

  PloS one 12 11 e0188093  2017年 [査読有り][通常論文]
   

  Non-muscle invasive bladder cancer is one of the most common tumors of the urinary tract. Despite the current multimodal therapy, recurrence and progression of disease have been challenging problems. We hereby introduced a new approach, ultrasound-assisted intravesical chemotherapy, intravesical instillation of chemotherapeutic agents and microbubbles followed by ultrasound exposure. We investigated the feasibility of the treatment for non-muscle invasive bladder cancer. In order to evaluate intracellular delivery and cytotoxic effect as a function to the thickness, we performed all experiments using a bladder cancer mimicking 3D culture model. Ultrasound-triggered microbubble cavitation increased both the intracellular platinum concentration and the cytotoxic effect of cisplatin at the thickness of 70 and 122 μm of the culture model. The duration of enhanced cytotoxic effect of cisplatin by ultrasound-triggered microbubble cavitation was approximately 1 hr. Based on the distance and duration of delivery, we further tested the feasibility of repetition of the treatment. Triple treatment increased the effective distance by 1.6-fold. Our results clearly showed spatial and temporal profile of delivery by ultrasound-triggered microbubble cavitation in a tumor-mimicking structure. Furthermore, we demonstrated that the increase in intracellular concentration results in the enhancement of the cytotoxic effect in a structure with the certain thickness. Repetition of ultrasound exposure would be treatment of choice in future clinical application. Our results suggest ultrasound-triggered microbubble cavitation can be repeatable and is promising for the local control of non-muscle invasive bladder cancer.
• Monitoring Lead (Pb) Pollution and Identifying Pb Pollution Sources in Japan Using Stable Pb Isotope Analysis with Kidneys of Wild Rats

  Hokuto Nakata, Shouta M. M. Nakayama, Balazs Oroszlany, Yoshinori Ikenaka, Hazuki Mizukawa, Kazuyuki Tanaka, Tsunehito Harunari, Tsutomu Tanikawa, Wageh Sobhy Darwish, Yared B. Yohannes, Aksorn Saengtienchai, Mayumi Ishizuka

  INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 14 1 2017年01月 [査読有り][通常論文]
   

  Although Japan has been considered to have little lead (Pb) pollution in modern times, the actual pollution situation is unclear. The present study aims to investigate the extent of Pb pollution and to identify the pollution sources in Japan using stable Pb isotope analysis with kidneys of wild rats. Wild brown (Rattus norvegicus, n = 43) and black (R. rattus, n = 98) rats were trapped from various sites in Japan. Mean Pb concentrations in the kidneys of rats from Okinawa (15.58 mg/kg, dry weight), Aichi (10.83), Niigata (10.62), Fukuoka (8.09), Ibaraki (5.06), Kyoto (4.58), Osaka (4.57), Kanagawa (3.42), and Tokyo (3.40) were above the threshold (2.50) for histological kidney changes. Similarly, compared with the previous report, it was regarded that even structural and functional kidney damage as well as neurotoxicity have spread among rats in Japan. Additionally, the possibility of human exposure to a high level of Pb was assumed. In regard to stable Pb isotope analysis, distinctive values of stable Pb isotope ratios (Pb-IRs) were detected in some kidney samples with Pb levels above 5.0 mg/kg. This result indicated that composite factors are involved in Pb pollution. However, the identification of a concrete pollution source has not been accomplished due to limited differences among previously reported values of Pb isotope composition in circulating Pb products. Namely, the current study established the limit of Pb isotope analysis for source identification. Further detailed research about monitoring Pb pollution in Japan and the demonstration of a novel method to identify Pb sources are needed.
• 非実験動物における化学物質代謝能の特徴と種差

  水川 葉月, 池中 良徳, 筧 麻友, 中山 翔太, 石塚 真由美

  薬学雑誌. 乙号 137 3 257 - 263 公益社団法人 日本薬学会 2017年 [査読有り][通常論文]
   

  The ability to metabolize xenobiotics in organisms has a wide degree of variation among organisms. This is caused by differences in the pattern of xenobiotic bioaccumulation among organisms, which affects their tolerance. It has been reported in the veterinary field that glucuronidation (UGT) activity in cats, acetylation activity in dogs and sulfation (SULT) activity in pigs are sub-vital in these species, respectively, and require close attention when prescribing the medicine. On the other hand, information about species differences in xenobiotics metabolism remains insufficient, especially in non-experimental animals. In the present study, we tried to elucidate xenobiotic metabolism ability, especially in phase II UGT conjugation of various non-experimental animals, by using newly constructed in vivo, in vitro and genomic techniques. The results indicated that marine mammals (Steller sea lion, northern fur seal, and Caspian seal) showed UGT activity as low as that in cats, which was significantly lower than in rats and dogs. Furthermore, UGT1A6 pseudogenes were found in the Steller sea lion and Northern fur seal; all Otariidae species are thought to have the UGT1A6 pseudogene as well. Environmental pollutants and drugs conjugated by UGT are increasing dramatically in the modern world, and their dispersal into the environment can be of great consequence to Carnivora species, whose low xenobiotic glucuronidation capacity makes them highly sensitive to these compounds.
  
• DDTs and other organochlorine pesticides in tissues of four bird species from the Rift Valley region, Ethiopia.

  Yared Beyene Yohannes, Yoshinori Ikenaka, Shouta M M Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  The Science of the total environment 574 1389 - 1395 2017年01月01日 [査読有り][通常論文]
   

  Despite the presence of a wide variety and number of birds, there is exceedingly little data on organochlorine pesticide (OCP) residues in birds inhabiting in Africa. In the present study, concentrations of dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexanes, drins, cyclodienes, and hexachlorobenzene were measured in liver, kidney, heart and brain of 4 bird species from the Rift Valley region, Ethiopia. Indoor residual spraying of DDT for malaria vector control, and indiscriminate and illegal use of pesticides underline the relevance of this study. Levels of ΣOCPs ranged from 1.87 to 4586ng/g wet weight, and the scavenger bird species Leptoptilos crumeniferus had the highest level in liver. In all tissues, contamination profiles of OCPs within the species were similar, with DDTs≫other OCPs. Among the DDTs, p,p'-DDE was the most abundant compound and had significantly a higher burden in all tissues. The risk characterization demonstrated potential risks to the studied birds associated with DDE exposure. Maximum hepatic levels of p,p'-DDE exceeded the levels reported to trigger adverse effects. The detection of p,p'-DDT in all bird tissues suggests the release of fresh DDT to the environment. This is the first study to assay OCPs in different tissues of birds from the Ethiopian Rift Valley region, and henceforth the data will serve as a reference data for future studies.
• The African hedgehog (Atelerix albiventris): Low phase I and phase II metabolism activities

  Aksorn Saengtienchai, Yoshinori Ikenaka, Nesta Bortey-Sam, Usuma Jermnark, Hazuki Mizukawa, Yusuke K. Kawai, Shouta M. M. Nakayama, Mayumi Ishizuka

  COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY 190 38 - 47 2016年12月 [査読有り][通常論文]
   

  The African hedgehog, Atelerix albiventris, is a spiny mammal that has become popular as an exotic pet in many countries. To elucidate the ability of hedgehogs to metabolize xenobiotics, the animals were exposed to polycyclic aromatic hydrocarbon, pyrene. The in vivo exposure study indicated that pyrene was biotransformed to glucuronide and sulfate conjugates, such as pyrene-l-glucuronide, pyrene-1-sulfate, and pyrenediol-sulfate, and excreted in the urine. Pyrene-l-glucuronide was the main metabolite, and limited sulfate conjugate excretion was observed. The main products excreted in feces were 1-hydroxypyrene and pyrene. Based on the results of the in vivo exposure study, in vitro enzymatic kinetic experiments were performed using various substrates and compared to rats and pigs. The enzyme efficiencies of cytochrome P450 (CYP)-mediated ethoxyresorufin 0-deethylase activity and warfarin 4 '-, 6-, and 8-hydroxylation activity in hedgehogs were lower than those of rats. Furthermore, UDP-glucuronosyltransferase activity in hedgehogs also had a lower Km value than that in pigs. Interestingly, the enzyme efficiencies of sulfation activity toward 1-hydroxypyrene and beta-estradiol in hedgehogs were significantly lower than those in pigs. These observations suggested that phenol and estrogen sulfotransferases may have limited roles in xenobiotic metabolism in hedgehogs. (C) 2016 Elsevier Inc. All rights reserved.
• Novel revelation of warfarin resistant mechanism in roof rats (Rattus rattus) using pharmacokinetic/pharmacodynamic analysis

  Kazuki Takeda, Yoshinori Ikenaka, Tsutomu Tanikawa, Kazuyuki D. Tanaka, Shouta M. M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY 134 1 - 7 2016年11月 [査読有り][通常論文]
   

  Roof rats (Rattus rattus) live mainly in human habitats. Heavy use of rodenticides, such as warfarin, has led to the development of drug resistance, making pest control difficult. There have been many reports regarding mutations of vitamin K epoxide reductase (VKOR), the target enzyme of warfarin, in resistant rats. However, it has been suggested there are other mechanisms of warfarin resistance. To confirm these possibilities, closed colonies of warfarin-susceptible roof rats (S) and resistant rats from Tokyo (R) were established, and the pharmacokinetics/ pharmacodynamics of warfarin in rats from both colonies was investigated. R rats had low levels of warfarin in serum and high clearance activity. These rats can rapidly metabolize warfarin by hydroxylation. The levels of accumulation in the organs were lower than those of S rats. R rats administered warfarin showed high expression levels of CYP2B, 2C, and 3A, which play roles in warfarin hydroxylation, and may explain the high clearance ability of R rats. The mechanism of warfarin resistance in roof rats from Tokyo involved not only mutation of VKOR but also high clearance ability due to high levels of CYP2B, 2C and 3A expression possibly induced by warfarin. (C) 2016 Elsevier Inc. All rights reserved.
• Excretion of polycyclic aromatic hydrocarbon metabolites (OH-PAHs) in cattle urine in Ghana

  Nesta Bortey-Sam, Yoshinori Ikenaka, Osei Akoto, Shouta M. M. Nakayama, Jemima Marfo, Aksorn Saengtienchai, Hazuki Mizukawa, Mayumi Ishizuka

  ENVIRONMENTAL POLLUTION 218 331 - 337 2016年11月 [査読有り][通常論文]
   

  Previous studies of polycyclic aromatic hydrocarbons (PAHs) in particulate matter, soils and livers of wild rats indicated that the city centre of Kumasi, Ghana has been severely polluted with high cancer potency. Cattle urine were therefore collected from Kumasi (urban) and Offinso (rural), Ghana: to determine concentrations of urinary PAH metabolites (OH-PAHs); and find their association with sex; and to estimate exposure of cattle to PAHs from the different sites. From the results, geometric mean concentrations (adjusted by specific gravity), GM(SG), showed that 2-OHNaphthalene (2-OHNap) was the most abundant OH-PAH in cattle urine from all study sites, and naphthalene-containing-mothballs might have contributed significantly to the levels. There was no significant difference between urinary OH-PAHs concentrations in cattle from urban and rural sites except for 2-OHPhe and 4-OHPhe, and similar to urban areas, rural sites could also be polluted with PAHs. GMSG of 2-OHNap in cattle urine in Kokote (21.9 +/- 6.51 ng/mL; a rural area), was significantly higher compared to the other sites followed by Oforikrom (4.15 +/- 4.37 ng/mL; urban). The GMSG concentration (ng/mL) of the sum of OH-PAHs decreased in the order, Kokote (44.7) > Oforikrom (7.87) > Saboa (6.98) > Santasi (6.68) > and Twumasen Estate (5.23). The high concentrations of urinary 2-OHNap, 2-OHPhe, 3-OHPhe and 4-OHPhe in Kokote indicated high PAHs exposure to cattle in this area or different/specific source of PAHs exposure. GMSG of 2-OHNap was significantly higher in male cattle compared to females while 1-9-OHPhe was significantly higher in females. (C) 2016 Published by Elsevier Ltd.
• Characterization of equine cytochrome P450: role of CYP3A in the metabolism of diazepam

  S. M. M. Nakayama, Y. Ikenaka, A. Hayami, H. Mizukawa, W. S. Darwish, K. P. Watanabe, Y. K. Kawai, M. Ishizuka

  JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS 39 5 478 - 487 2016年10月 [査読有り][通常論文]
   

  Research on drug metabolism and pharmacokinetics in large animal species including the horse is scarce because of the challenges in conducting in vivo studies. The metabolic reactions catalyzed by cytochrome P450s (CYPs) are central to drug pharmacokinetics. This study elucidated the characteristics of equine CYPs using diazepam (DZP) as a model compound as this drug is widely used as an anesthetic and sedative in horses, and is principally metabolized by CYPs. Diazepam metabolic activities were measured in vitro using horse and rat liver microsomes to clarify the species differences in enzyme kinetic parameters of each metabolite (temazepam [TMZ], nordiazepam [NDZ], p-hydroxydiazepam [p-OH-DZP], and oxazepam [OXZ]). In both species microsomes, TMZ was the major metabolite, but the formation rate of p-OH-DZP was significantly less in the horse. Inhibition assays with a CYP-specific inhibitors and antibody suggested that CYP3A was the main enzyme responsible for DZP metabolism in horse. Four recombinant equine CYP3A isoforms expressed in Cos-7 cells showed that CYP3A96, CYP3A94, and CYP3A89 were important for TMZ formation, whereas CYP3A97 exhibited more limited activity. Phylogenetic analysis suggested diversification of CYP3As in each mammalian order. Further study is needed to elucidate functional characteristics of each equine CYP3A isoform for effective use of diazepam in horses.
• ポリ塩化ビフェニル(PCBs)のin vivo暴露によるネコの異物代謝解明と甲状腺ホルモンへの影響評価

  水川 葉月, 前原 美咲, 横山 望, 市居 修, 滝口 満喜, 野見山 桂, 西川 博之, 池中 良徳, 中山 翔太, 高口 倖暉, 田辺 信介, 石塚 真由美

  The Journal of Toxicological Sciences 41 Suppl. S215 - S215 (一社)日本毒性学会 2016年06月 [査読有り][通常論文]
  
• Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats

  Yoshihiro Nishiyama, Shouta M. M. Nakayama, Kensuke P. Watanabe, Yusuke K. Kawai, Marumi Ohno, Yoshinori Ikenaka, Mayumi Ishizuka

  JOURNAL OF VETERINARY MEDICAL SCIENCE 78 4 675 - 680 2016年04月 [査読有り][通常論文]
   

  Rat cytochrome P450 (CYP) exhibits inter-strain differences, but their analysis has been scattered across studies under different conditions. To identify these strain differences in CYP more comprehensively, mRNA expression, protein expression and metabolic activity among Wistar (WI), Sprague Dawley (SD), Dark Agouti (DA) and Brown Norway (BN) rats were compared. The mRNA level and enzymatic activity of CYP1A1 were highest in SD rats. The rank order of Cyp3a2 mRNA expression mirrored its protein expression, i.e., DA>BN>SD>WI, and was similar to the CYP3A2-dependent warfarin metabolic activity, i.e., DA>SD>BN>WI. These results suggest that the strain differences in CYP3A2 enzymatic activity are caused by differences in mRNA expression. Cyp2b1 mRNA levels, which were higher in DA rats, did not correlate with its protein expression or enzymatic activity. This suggests that the strain differences in enzymatic activity are not related to Cyp2b1 mRNA expression. In conclusion, WI rats tended to have the lowest CYP1A1, 2B1 and 3A2 mRNA expression, protein expression and enzymatic activity among the strains. In addition, SD rats had the highest CYP1A1 mRNA expression and activity, while DA rats had higher CYP2B1 and CYP3A2 mRNA and protein expression. These inter-strain differences in CYP could influence pharmacokinetic considerations in preclinical toxicological studies.
• Bioaccumulation and human health risk assessment of DDT and other organochlorine pesticides in an apex aquatic predator from a premier conservation area

  Ruan Gerber, Nico J. Smit, Johan H. J. Van Vuren, Shouta M. M. Nakayama, Yared B. Yohannes, Yoshinori Ikenaka, Mayumi Ishizuka, Victor Wepener

  SCIENCE OF THE TOTAL ENVIRONMENT 550 522 - 533 2016年04月 [査読有り][通常論文]
   

  With the second highest gross domestic product in Africa, South Africa is known to have a high pesticide usage, including the highly persistent and banned group of organochlorine pesticides (OCPs). South Africa is also one of few countries to still actively spray DDT as malaria vector control. The aim of the study was to determine the degree to which aquatic biota in selected rivers of the world renowned Kruger National Park (KNP) arc exposed to by use of OCPs in the catchments outside the KNP and how this exposure relates to human health. Tigerfish (Hydrocynus vittatus) arc economically important apex predators and was selected as bioindicator for this study. Fish were sampled from the KNP sections of the Luvuvhu, Letaba and Olifants rivers during the high and low flow periods from 2010 to 2011 within the KNP and 19 OCPs were determined in muscle tissue using GC-ECD techniques. Significant flow related and spatial OCP bioaccumulation was observed. Tigerfish from the Luvuvhu River displayed the highest OCP bioaccumulation. Concentrations of the majority of the OCPs including the DDTs were the highest levels ever recorded from South African freshwater systems and in many cases the concentrations were higher than most contaminated areas from around the world. The concentrations found in H. vittatus muscle also exceeded maximum residue levels in edible fat as set by the European Union. The health risk assessment also demonstrated that the levels of OCPs pose very high cancer risks to the local populations consuming tigerfish, as high as 2 in 10 increased risk factor. This is of concern not only when managing the water resources of the conservation area but also for surrounding communities consuming freshwater fish. Contaminants enter the park from outside the borders and pose potential risks to the mandated conservation of aquatic biota within the KNP. (C) 2016 Elsevier B.V. All rights reserved.
• Distribution and health risk assessment of organochlorine pesticides (OCPs) residue in edible cattle tissues from northeastern part of Egypt: High accumulation level of OCPs in tongue

  Abdallah Fikry A. Mahmoud, Yoshinori Ikenaka, Yared B. Yohannes, Wageh S. Darwish, Elsaid A. Eldaly, Alaa Eldin M. A. Morshdy, Shouta M. M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  CHEMOSPHERE 144 1365 - 1371 2016年02月 [査読有り][通常論文]
   

  Food consumption is an important route of human exposure to organochlorine pesticides (OCPs). In order to assess the potential human health risks associated with OCPs, edible cattle tissues (liver, kidney and tongue) were collected from three slaughter houses in Mansoura, Zagazig and Ismailia cities, Egypt. Levels of 22 OCPs such as hexachlorocyclohexanes (HCHs), dichlorodiphenyltrichloroethanes (DDTs), aldrin, dieldrin and endrin (Drins), chlordanes (CHLs), heptachlors (HPTs) and hexachlorobenzene (HCB) residues were investigated. Among the investigated OCPs, HCHs represented the most dominant group with high proportions of gamma-HCH isomer (53-91% of total HCHs). Mansoura city had the highest OCPs contamination load ranged from 0.1 to 2827 ng g(-1) lw (lipid weight). Surprisingly, tongue samples collected from Mansoura showed the highest concentration of HCHs (448 ng g(-1) lw) in comparison to liver (152 ng g(-1) lw) and kidney (266 ng g(-1) lw). Generally, contamination pattern of OCPs was in the order of HCHs > Drins > CHLs > DDTs congruent to HCB and HPTs. Estimated daily intakes (EDIs) through dietary consumption of cattle tissues were lower than the recommended acceptable daily intakes (ADIs) established by FAO/WHO. However, the hazard ratios (HRs) based on cancer risk were greater than 1.0 for HCHs based on the average and 95th centile concentrations, indicating carcinogenic effects to consumers through cattle tissues consumption. (C) 2015 Elsevier Ltd. All rights reserved.
• β-carotene and retinol contents in the meat of herbivorous ungulates with a special reference to their public health importance.

  Darwish WS, Ikenaka Y, Morshdy AE, Eldesoky KI, Nakayama S, Mizukawa H, Ishizuka M

  The Journal of veterinary medical science 78 2 351 - 354 2016年02月 [査読有り][通常論文]
   

  The aim of this study was to estimate total carotenoids, beta-carotene and retinol concentrations in the livers and muscles of some ungulates (cattle, buffalo, sheep, goats and horses) in comparison with the Wistar rats as a control. Cattle and horses had the highest contents of total carotenoids and beta-carotene. Unexpectedly, sheep was the highest accumulator of retinol with a mean concentration of 203 +/- 23.34 mu g/g, while the least accumulator was buffalo, having a mean value of 58.28 +/- 13.77 mu g/g. Livers had higher contents of the examined phytochemicals than muscles. Consumption of these tissues may provide human with some needs from these important phytochemicals, though ingestion of livers, especially that of the sheep, is not advisable for the pregnant women.
• Reliability of stable Pb isotopes to identify Pb sources and verifying biological fractionation of Pb isotopes in goats and chickens

  Hokuto Nakata, Shouta M. M. Nakayama, John Yabe, Allan Liazambi, Hazuki Mizukawa, Wageh Sobhy Darwish, Yoshinori Ikenaka, Mayumi Ishizuka

  ENVIRONMENTAL POLLUTION 208 Pt.B 395 - 403 2016年01月 [査読有り][通常論文]
   

  Stable Pb isotope ratios (Pb-IRs) have been recognized as an efficient tool for identifying sources. This study carried out at Kabwe mining area, Zambia, to elucidate the presence or absence of Pb isotope fractionation in goat and chicken, to evaluate the reliability of identifying Pb pollution sources via analysis of Pb-IRs, and to assess whether a threshold for blood Pb levels (Pb-B) for biological fractionation was present The variation of Pb-IRs in goat decreased with an increase in Pb-B and were fixed at certain values close to those of the dominant source of Pb exposure at Pb-B > 5 mu g/dL. However, chickens did not show a clear relationship for Pb-IRs against Pb-B, or a fractionation threshold. Given these, the biological fractionation of Pb isotopes should not occur in chickens but in goats, and the threshold for triggering biological fractionation is at around 5 mu g/dL of Pb-B in goats. (C) 2015 Elsevier Ltd. All rights reserved.
• Constitutive Effects of Lead on Aryl Hydrocarbon Receptor Gene Battery and Protection by β-carotene and Ascorbic Acid in Human HepG2 Cells.

  Darwish WS, Ikenaka Y, Nakayama SM, Mizukawa H, Ishizuka M

  Journal of food science 81 1 T275 - T281 2016年01月 [査読有り][通常論文]
   

  Lead (Pb) is an environmental pollutant that can get entry into human body through contaminated foods, drinks, and inhaled air leading to severe biological consequences, and has been responsible for many deaths worldwide. The objectives of this study were 1st to investigate the modulatory effects of environmentally relevant concentrations of Pb on AhR gene battery, which is controlling xenobiotics metabolism. 2nd, trials to reduce Pb-induced adverse effects were done using some phytochemicals like beta-carotene or ascorbic acid. Human hepatoma (HepG2) cell lines were exposed to a wide range of Pb concentrations varying from physiological to toxic levels (0 to 10 mg/L) for 24 h. High Pb concentrations (1 to 10 mg/L) significantly reduced phase I (CYP1A1 and 1A2) and phase II (UGT1A6 and NQO1) xenobiotic metabolizing enzyme mRNA expression in a mechanistic manner through the AhR regulation pathway. Additionally, these Pb concentrations induced oxidative stress in HepG2 cells in terms of production of reactive oxygen species (ROS) and induced heme oxygenase-1 mRNA expression in a concentration-dependent phenomenon. Coexposure of HepG2 cells to physiological concentrations of some micronutrients, like beta-carotene (10 mu M) or ascorbic acid (0.1 mM), along with Pb (1 mg/L) for 24 h significantly reduced the levels of ROS production and recovered AhR mRNA expression into the normal levels. Thus, consumption of foods rich in these micronutrients may help to reduce the adverse effects of lead in areas with high levels of pollution.
• Organohalogen Compounds in Pet Dog and Cat: Do Pets Biotransform Natural Brominated Products in Food to Harmful Hydroxlated Substances?

  Hazuki Mizukawa, Kei Nomiyama, Susumu Nakatsu, Hisato Iwata, Jean Yoo, Akira Kubota, Miyuki Yamamoto, Mayumi Ishizuka, Yoshinori Ikenaka, Shouta M. M. Nakayama, Tatsuya Kunisue, Shinsuke Tanabe

  ENVIRONMENTAL SCIENCE & TECHNOLOGY 50 1 444 - 452 2016年01月 [査読有り][通常論文]
   

  There are growing concerns about the increase in hyperthyroidism in pet cats due to exposure to organo-halogen contaminants and their hydroxylated metabolites. This study investigated the blood contaminants polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) and their hydroxylated and methoxylated derivatives (OH-PCBs, OH-PBDEs, and MeO-PBDEs), in pet dogs and cats. We also measured the residue levels of these compounds in commercially available pet foods. Chemical analyses of PCBs and OH-PCBs showed that the OH-PCB levels were 1 to 2 orders of magnitude lower in cat and dog food products than in their blood, suggesting that the origin of OH-PCBs in pet dogs and cats is PCBs ingested with their food. The major congeners of OH-/MeO-PBDEs identified in both pet food products and blood were natural products (60H-/MeO-BDE47 and 2'OH-/MeO-BDE68) from marine organisms. In particular, higher concentrations of 60H-BDE47 than 2'OH-BDE68 and two MeO-PBDE congeners were observed in the cat blood, although MeO-BDEs were dominant in cat foods, suggesting the efficient biotransformation of 60H-BDE47 from 6MeO-BDE47 in cats. We performed in vitro demethylation experiments to confirm the biotransformation of MeO-PBDEs to OH-PBDEs using liver microsomes. The results showed that 6MeO-BDE47 and 2'MeO-BDE68 were demethylated to 60H-BDE47 and 2'OH-BDE68 in both animals, whereas no hydroxylated metabolite from BDE47 was detected. The present study suggests that pet cats are exposed to MeO-PBDEs through cat food products containing fish flavors and that the OH-PBDEs in cat blood are derived from the CYP-dependent demethylation of naturally occurring MeO-PBDE congeners, not from the hydroxylation of PBDEs.
• Application of a Sediment Quality Index for the assessment and monitoring of metals and organochlorines in a premier conservation area

  Ruan Gerber, Nico J. Smit, Johan H. J. van Vuren, Shouta M. M. Nakayama, Yared B. Yohannes, Yoshinori Ikenaka, Mayumi Ishizuka, Victor Wepener

  ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH 22 24 19971 - 19989 2015年12月 [査読有り][通常論文]
   

  The physical and chemical characteristics of surface sediments from a leading conservation area, namely the Kruger National Park, were determined in order to identify potential stressors in the systems that may contribute to overall deterioration in sediment quality within the reserve, leading to potential threats to the aquatic biota conserved within these stretches of river. Sediment samples were collected during four surveys (two low flow and two high flow) from 2009 to 2011. Samples were analysed for organic content, grain size determination, metals and various organochlorine pesticides. Results indicated that the Olifants River sediments did not show any great improvement over the years and point towards the continued input of pollutants into this system. Sediment quality in the Luvuvhu and Letaba Rivers is better than that of sediments from the Olifants River in terms of metals, but metal concentrations are still comparable and point towards anthropogenic inputs of metals into these rivers. Even though the data indicate that these systems are being contaminated with both metals and organochlorine pesticides (OCPs), levels were still below contaminated sediments from around the globe. Sediment Quality Index scores showed that the sediment quality of these rivers is in a relatively good state. High metal concentrations were the drivers behind lowered sediment quality, and in some cases certain OCPs played a role. Both metals and OCP concentrations were highly correlated with finer grain sizes. Sediment assessments are not routinely applied in South Africa resulting in very little reference or background data available for the area. The metal concentrations for the study area were generally lower than those for other studies in more polluted regions. The study also contributes to the available knowledge on surrounding metal pollution in riverine sediments in South Africa.
• Accumulation properties of inorganic mercury and organic mercury in the red-crowned crane Grus japonensis in east Hokkaido, Japan

  Hiroki Teraoka, Erika Okamoto, Moe Kudo, Shouta M. M. Nakayama, Yoshinori Ikenaka, Mayumi Ishizuka, Tetsuya Endo, Takio Kitazawa, Takeo Hiraga

  ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 122 557 - 564 2015年12月 [査読有り][通常論文]
   

  The red-crowned (Japanese) crane Grus japonensis is native to east Hokkaido, Japan, in contrast to the East Asia mainland. Previously, we reported that red-crowned cranes in Hokkaido were highly contaminated with mercury in the 1990s and that the contamination rapidly decreased to a moderate level in the 2000s. In the present study, we determined levels of organic mercury (O-Hg) in the liver and kidney of cranes in east Hokkaido in comparison with levels of total mercury (T-Hg). T-Hg levels in the kidneys were higher than those in the livers in adults but not in subadults and juveniles; however, the reverse was the case for O-Hg even for adults. The ratio of O-Hg to T-Hg in both the liver and kidney decreased as T-Hg increased in the three developmental stages. While the ratios of O-Hg to T-Hg in the liver and kidney of adults were significantly lower than those of juveniles, the ratios were similar for adults and juveniles in a lower range of T-Hg. The ratio of selenium (Se) to T-Hg decreased as T-Hg increased in both the liver and kidney, irrespective of stages. Mercury burdens in feathers were about 59% and 67% of the total body burdens for juveniles and adults, respectively. Furthermore, ratios of carbon and nitrogen stable isotopes to T-Hg varied greatly, with no relation to mercury level in the liver. The results suggest slow accumulation of inorganic mercury in the kidney of red-crowned cranes in east Hokkaido, Japan. (C) 2015 Elsevier Inc. All rights reserved.
• Relationship between Urinary N-Desmethyl-Acetamiprid and Typical Symptoms including Neurological Findings: A Prevalence Case-Control Study

  Jemima Tiwaa Mario, Kazutoshi Fujioka, Yoshinori Ikenaka, Shouta M. M. Nakayama, Hazuki Mizukawa, Yoshiko Aoyama, Mayumi Ishizuka, Kumiko Taira

  PLOS ONE 10 11 e0142172  2015年11月 [査読有り][通常論文]
   

  Neonicotinoid insecticides are nicotinic acetylcholine receptor agonists used worldwide. Their environmental health effects including neurotoxicity are of concern. We previously determined a metabolite of acetamiprid, N-desmethyl-acetamiprid in the urine of a patient, who exhibited some typical symptoms including neurological findings. We sought to investigate the association between urinary N-desmethyl-acetamiprid and the symptoms by a prevalence case-control study. Spot urine samples were collected from 35 symptomatic patients of unknown origin and 50 non-symptomatic volunteers (non-symptomatic group, NSG, 4-87 year-old). Patients with recent memory loss, finger tremor, and more than five of six symptoms (headache, general fatigue, palpitation/chest pain, abdominal pain, muscle pain/weakness/spasm, and cough) were in the typical symptomatic group (TSG, n = 19, 5-69 year-old); the rest were in the atypical symptomatic group (ASG, n = 16, 5-78 year-old). N-desmethyl-acetamiprid and six neonicotinoids in the urine were quantified by liquid chromatography-tandem mass spectrometry. The detection of N-desmethyl-acetamiprid was the most frequent and highest in TSG (47.4%, 6.0 ppb (frequency, maximum)), followed by in ASG (12.5%, 4.4 ppb) and in NSG (6.0%, 2.2 ppb), however acetamiprid was not detected. Thiamethoxam was detected in TSG (31.6%, 1.4 ppb), in ASG (6.3%, 1.9 ppb), but not in NSG. Nitenpyram was detected in TSG (10.5%, 1.2 ppb), in ASG (6.3%, not quantified) and in NSG (2.0%, not quantified). Clothianidin was only detected in ASG (6.3%, not quantified), and in NSG (2.0%, 1.6 ppb). Thiacloprid was detected in ASG (6.3%, 0.1 ppb). The cases in TSG with detection of N-desmethyl-acetamiprid and thiamethoxam were aged 5 to 62 years and 13 to 62 years, respectively. Detection of N-desmethyl-acetamiprid was associated with increased prevalence of the symptoms (odds ratio: 14, 95% confidence interval: 3.5-57). Urinary N-desmethyl-acetamiprid can be used as a biomarker for environmental exposure to acetamiprid. Further multi-centered clinical research in larger patients groups with more metabolites analysis is needed.
• Mutagenicity of modelled-heat-treated meat extracts: Mutagenicity assay, analysis and mechanism of mutagenesis

  Wageh Sobhy Darwish, Yoshinori Ikenaka, Shouta Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  JAPANESE JOURNAL OF VETERINARY RESEARCH 63 4 173 - 182 2015年11月 [査読有り][通常論文]
   

  Cooking of meat usually aims in producing microbiologically safe food suitable for human consumption. However, doing so at such high temperatures may produce some cooking toxicants or mutagens. The objectives of this study were to investigate the mutagenicity of modelled-heat-treated meat after different cooking methods (boiling, pan-frying and charcoal grilling) using Ames Salmonella typhimurium mutagenicity assay. In addition, the content of benzo[a]pyrene (B[a]P) in the meat extracts prepared under different cooking methods were measured using HPLC. In a trial to investigate the causes behind the mutagenicity of different meat extracts, HepG2 cell line was exposed to different modelled-heat-treated meat extracts. mRNA expression levels of various phase I and II xenobiotic metabolizing enzymes (XMEs) were examined using real time PCR. The results obtained declared that pan-fried and charcoal grilled-meat extracts significantly induced production of histidine+ revertants in the Ames mutagenicity assay. Grilled-meat extracts had the highest residual concentrations of B[a]P followed by pan-fried-meat, boiled meat and raw meat extracts, respectively. Induction of XMEs especially CYP1A1, CYP1A2 and NQO1 may contribute to the mutagenic ability of these extracts. It is highly advisable to control cooking temperature, time and method in order to reduce cooked-meat mutagens.
• Cytochrome P450-mediated warfarin metabolic ability is not a critical determinant of warfarin sensitivity in avian species: In vitro assays in several birds and in vivo assays in chicken

  Kensuke P. Watanabe, Minami Kawata, Yoshinori Ikenaka, Shouta M. M. Nakayama, Chihiro Ishii, Wageh Sobhi Darwish, Aksorn Saengtienchai, Hazuki Mizukawa, Mayumi Ishizuka

  ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY 34 10 2328 - 2334 2015年10月 [査読有り][通常論文]
   

  Coumarin-derivative anticoagulant rodenticides used for rodent control are posing a serious risk to wild bird populations. For warfarin, a classic coumarin derivative, chickens have a high median lethal dose (LD50), whereas mammalian species generally have much lower LD50. Large interspecies differences in sensitivity to warfarin are to be expected. The authors previously reported substantial differences in warfarin metabolism among avian species; however, the actual in vivo pharmacokinetics have yet to be elucidated, even in the chicken. In the present study, the authors sought to provide an in-depth characterization of warfarin metabolism in birds using in vivo and in vitro approaches. A kinetic analysis of warfarin metabolism was performed using liver microsomes of 4 avian species, and the metabolic abilities of the chicken and crow were much higher in comparison with those of the mallard and ostrich. Analysis of in vivo metabolites from chickens showed that excretions predominantly consisted of 4-hydroxywarfarin, which was consistent with the in vitro results. Pharmacokinetic analysis suggested that chickens have an unexpectedly long half-life despite showing high metabolic ability in vitro. The results suggest that the half-life of warfarin in other bird species could be longer than that in the chicken and that warfarin metabolism may not be a critical determinant of species differences with respect to warfarin sensitivity. Environ Toxicol Chem 2015;34:2328-2334. (c) 2015 SETAC
• Metal extent in blood of livestock from Dandora dumping site, Kenya: Source identification of Pb exposure by stable isotope analysis

  Hokuto Nakata, Shouta M. M. Nakayama, Yoshinori Ikenaka, Hazuki Mizukawa, Chihiro Ishii, Yared B. Yohannes, Satoru Konnai, Wageh Sobhy Darwish, Mayumi Ishizuka

  ENVIRONMENTAL POLLUTION 205 8 - 15 2015年10月 [査読有り][通常論文]
   

  Nairobi city in Kenya produces 2000 tons/day of garbage, and most of it is dumped onto the Dandora dumping site, home to a quarter-million residents. This study was conducted (1) to assess the contamination levels of nine metals and a metalloid (arsenic) in the blood of pigs, goats, sheep and cattle from Dandora, and (2) to identify a possible source of lead (Pb) pollution. Cadmium (Cd, 0.17-435 mu g/kg, dry-wt) and Pb (90-2710 mu g/kg) levels in blood were generally high, suggesting human exposure to Cd through livestock consumption and Pb poisoning among pigs (2600 mu g/kg) and cattle (354 mu g/kg). Results of Pb isotope ratios indicated that the major exposure route might differ among species. Our results also suggested a possibility that the residents in Dandora have been exposed to the metals through livestock consumption. (C) 2015 Elsevier Ltd. All rights reserved.
• Characterization and tissue distribution of conjugated metabolites of pyrene in the rat

  Aksorn Saengtienchai, Yoshinori Ikenaka, Wageh Sobhy Darwish, Shouta M. M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  JOURNAL OF VETERINARY MEDICAL SCIENCE 77 10 1261 - 1267 2015年10月 [査読有り][通常論文]
   

  Pyrene (PY) is a polycyclic aromatic hydrocarbon (PAH) that is often used as a biomarker for human and wildlife exposure to PAHs. As the metabolites of PAHs, similar to their parent compounds, pose public health risks, it is necessary to study their characteristics and tissue-specific distribution. The present study was performed to experimentally characterize PY metabolites and analyze the tissue-specific distribution of the conjugated metabolites after oral administration of PY to rats. PY metabolites, such as pyrenediol-disulfate (PYdiol-diS), pyrenediol-sulfate (PYdiol-S), pyrene-1-sufate (PYOS), pyrene-l-glucuronide (PYOG) and 1-hydroxypyrene (PYOH), were detected in rat urine. Although glucuronide conjugate was the predominant metabolite, the metabolite composition varied among tissues. Interestingly, the proportion of PYOH was high in the large intestine. Furthermore, PYOH was the only PY metabolite detected in feces.
• Uridine Diphosphate-Glucuronosyltransferase (UGT) Xenobiotic Metabolizing Activity and Genetic Evolution in Pinniped Species

  Mayu Kakehi, Yoshinori Ikenaka, Shouta M. M. Nakayama, Yusuke K. Kawai, Kensuke P. Watanabe, Hazuki Mizukawa, Kei Nomiyama, Shinsuke Tanabe, Mayumi Ishizuka

  TOXICOLOGICAL SCIENCES 147 2 360 - 369 2015年10月 [査読有り][通常論文]
   

  There are various interspecies differences in xenobiotic-metabolizing enzymes. It is known that cats show slow glucuronidation of drugs such as acetaminophen and strong side effects due to the UGT1A6 pseudogene. Recently, the UGT1A6 pseudogene was found in the Northern elephant seal and Otariidae was suggested to be UGT1A6-deficient. From the results of measurements of uridine diphosphate-glucuronosyltransferase (UGT) activity using liver microsomes, the Steller sea lion, Northern fur seal, and Caspian seal showed UGT activity toward 1-hydroxypyrene and acetaminophen as low as in cats, which was significantly lower than in rat and dog. Furthermore, UGT1A6 pseudogenes were found in Steller sea lion and Northern fur seal, and all Otariidae species were suggested to have the UGT1A6 pseudogene. The UGT1 family genes appear to have undergone birth-and-death evolution based on a phylogenetic and synteny analysis of the UGT1 family in mammals including Carnivora. UGT1A2-1A5 and UGT1A7-1A10 are paralogous genes to UGT1A1 and UGTA6, respectively, and their numbers were lower in cat, ferret and Pacific walrus than in human, rat, and dog. Felidae and Pinnipedia, which are less exposed to natural xenobiotics such as plant-derived toxins due to their carnivorous diet, have experienced fewer gene duplications of xenobiotic-metabolizing UGT genes, and even possess UGT1A6 pseudogenes. Artificial environmental pollutants and drugs conjugated by UGT are increasing dramatically, and their elimination to the environment can be of great consequence to cat and Pinnipedia species, whose low xenobiotic glucuronidation capacity makes them highly sensitive to these compounds.
• Ecological Risk of Heavy Metals and a Metalloid in Agricultural Soils in Tarkwa, Ghana

  Nesta Bortey-Sam, Shouta M. M. Nakayama, Osei Akoto, Yoshinori Ikenaka, Elvis Baidoo, Hazuki Mizukawa, Mayumi Ishizuka

  INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 12 9 11448 - 11465 2015年09月 [査読有り][通常論文]
   

  Heavy metals and a metalloid in agricultural soils in 19 communities in Tarkwa were analyzed to assess the potential ecological risk. A total of 147 soil samples were collected in June, 2012 and analyzed for As, Cd, Co, Cr, Cu, Hg, Ni, Pb and Zn. Mean concentrations (mg/kg dw) of heavy metals in the communities decreased in order of Zn (39) ? Cr (21) ? Pb (7.2) ? Cu (6.2) ? As (4.4) ? Ni (3.7) ? Co (1.8) ? Hg (0.32) ? Cd (0.050). Correlations among heavy metals and soil properties indicated that soil organic matter could have substantial influence on the total contents of these metals in soil. From the results, integrated pollution (C-deg) in some communities such as, Wangarakrom (11), Badukrom (13) and T-Tamso (17) indicated high pollution with toxic metals, especially from As and Hg. Potential ecological risk (RI) indices indicated low (Mile 7) to high risks (Wangarakrom; Badukrom) of metals. Based on pollution coefficient (C-f(i)), C-deg, monomial ecological risk (E-r(i)) and RI, the investigated soils fall within low to high contamination and risk of heavy metals to the ecological system especially plants, soil invertebrates and/or mammalian wildlife. This represented moderate potential ecological risk in the study area, and mining activities have played a significant role.
• Accumulation of Heavy Metals and Metalloid in Foodstuffs from Agricultural Soils around Tarkwa Area in Ghana, and Associated Human Health Risks

  Nesta Bortey-Sam, Shouta M. M. Nakayama, Osei Akoto, Yoshinori Ikenaka, Julius N. Fobil, Elvis Baidoo, Hazuki Mizukawa, Mayumi Ishizuka

  INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 12 8 8811 - 8827 2015年08月 [査読有り][通常論文]
   

  This study was carried out to assess the extent of heavy metals and metalloid accumulation from agricultural soils to foodstuffs (viz, M. esculenta (cassava) and Musa paradisiaca (plantain)) around thirteen neighboring communities within Tarkwa, Ghana; and to estimate the human health risk associated with consumption of these foodstuffs. Concentrations of As, Cd, Co, Cr, Cu, Ni, Pb, and Zn were measured with an inductively coupled plasma-mass spectrometer and mercury analysis was done using a mercury analyzer. From the results, 30% of cassava samples collected, contained higher concentrations of Pb when compared to Codex Alimentarius Commission standard values. Bioconcentration factor indicated that Ni had higher capacity of absorption into food crops from soil than the other heavy metals. For both children and adults, the target hazard quotient (THQ) of Pb in cassava in communities such as Techiman, Wangarakrom, Samahu, and Tebe (only children) were greater than 1, which is defined as an acceptable risk value. This indicated that residents could be exposed to significant health risks associated with cassava consumption.
• Levels, potential sources and human health risk of polycyclic aromatic hydrocarbons (PAHs) in particulate matter (PM10) in Kumasi, Ghana

  Nesta Bortey-Sam, Yoshinori Ikenaka, Osei Akoto, Shouta M. M. Nakayama, Yared Beyene Yohannes, Elvis Baidoo, Hazuki Mizukawa, Mayumi Ishizuka

  ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH 22 13 9658 - 9667 2015年07月 [査読有り][通常論文]
   

  Airborne particulate samples were collected on quartz filters to determine the concentrations, sources and health risks of polycyclic aromatic hydrocarbons (PAHs) in air in Kumasi, Ghana. A total of 32 air samples were collected in Kwame Nkrumah University of Science and Technology (KNUST) campus (pristine site) and city centre (CC). Samples were extracted with 1:2v/v acetone/hexane mixture prior to GC-MS analyses. The sum of concentrations of 17 PAHs in air ranged from 0.51 to 16 (KNUST) and 19-38 ng/m(3) (CC). The concentration of benzo[a]pyrene, BaP, ranged from below detection limit to 0.08 ng/m(3) (KNUST) and 1.6 to 5.6 ng/m(3) (CC). Chemical mass balance model showed that PAHs in air in Kumasi were mainly from fuel combustion. The total BaP equivalent concentration (BaPeq) in CC was 18 times higher compared to KNUST; based on the European Legislation and Swedish and UK Standards for BaP in air, CC could be classified as highly polluted. Estimated carcinogenicity of PAHs in terms of BaPeq indicated that BaP was the principal PAH contributor in CC (70 %). Health risk to adults and children associated with PAH inhalation was assessed by taking into account the lifetime average daily dose and corresponding incremental lifetime cancer risk (ILCR). The ILCR was within the acceptable range (10(-6) to 10(-4)), indicating low health risk to residents.
• Health risk assessment of heavy metals and metalloid in drinking water from communities near gold mines in Tarkwa, Ghana

  Nesta Bortey-Sam, Shouta M. M. Nakayama, Yoshinori Ikenaka, Osei Akoto, Elvis Baidoo, Hazuki Mizukawa, Mayumi Ishizuka

  ENVIRONMENTAL MONITORING AND ASSESSMENT 187 7 1 - 12 2015年07月 [査読有り][通常論文]
   

  Concentrations of heavy metals and metalloid in borehole drinking water from 18 communities in Tarkwa, Ghana, were measured to assess the health risk associated with its consumption. Mean concentrations of heavy metals (mu g/L) exceeded recommended values in some communities. If we take into consideration the additive effect of heavy metals and metalloid, then oral hazard index (HI) results raise concerns about the noncarcinogenic adverse health effects of drinking groundwater in Huniso. According to the US Environmental Protection Agency's (USEPA) guidelines, HI values indicating noncarcinogenic health risk for adults and children in Huniso were 0.781 (low risk) and 1.08 (medium risk), respectively. The cancer risk due to cadmium (Cd) exposure in adults and children in the sampled communities was very low. However, the average risk values of arsenic (As) for adults and children through drinking borehole water in the communities indicated medium cancer risk, but high cancer risk in some communities such as Samahu and Mile 7. Based on the USEPA assessment, the average cancer risk values of As for adults (3.65E-05) and children (5.08E-05) indicated three (adults) and five (children) cases of neoplasm in a hundred thousand inhabitants. The results of this study showed that residents in Tarkwa who use and drink water from boreholes could be at serious risk from exposure to these heavy metals and metalloid.
• Metabolic Activation of Heterocyclic Amines and Expression of Xenobiotic-Metabolizing Enzymes in the Gastrointestinal Tract of Rats

  Wageh S. Darwish, Shouta M. M. Nakayama, Yuumi Itotani, Marumi Ohno, Yoshinori Ikenaka, Mayumi Ishizuka

  JOURNAL OF FOOD SCIENCE 80 7 T1627 - T1632 2015年07月 [査読有り][通常論文]
   

  Heterocyclic amines get entry into human body mainly through ingestion of pan-fried meats cooked at high temperatures. Exposure of the gastrointestinal tract (GIT) to ingested xenobiotics prior to delivery to the liver may lead to metabolic activation, which may explain the high incidence of GIT carcinogenesis. Therefore, this study investigated the mutagenic activation of 2 heterocyclic amines, 2-aminoanthracene (2-AA) and 3-amino-1-methyl-5H-prydo[4,3-b]indole (Trp-P-2), in the GIT of rats. In addition, the constitutive mRNA expression profiles of xenobiotic-metabolizing enzymes (XMEs) in the GIT of rats were examined. Metabolic activation of 2-AA was detected in all GIT tissues except the duodenum and rectum, and it was detected at high levels in the ileum and cecum. Furthermore, we revealed high metabolic activation of 2-AA and Trp-P-2 in the jejunum. The mRNA expression of phase I and II enzymes in rat GIT corresponded with their mutagenic activation ability. In conclusion, our results suggest that different expression levels of XME among GIT tissues may contribute to the tissue-specific differences in metabolic activation of xenobiotics such as heterocyclic amines in rats. Practical Application This study declares mutagenic activation of 2 heterocyclic amines namely 2-aminoanthracene (2-AA) and 3-amino-1-methyl-5H-prydo[4,3-b]indole (Trp-P-2), in the gastrointestinal tract (GIT) of rats. In addition, results obtained in this study suggest that GIT tissue-specific expression of xenobiotic metabolizing enzymes may contribute to the tissue-specific mutagenesis/carcinogenesis.
• Are red gourami (Colisa labiosa) low xenobiotic metabolizers? Elucidation of in vivo pharmacokinetics of pyrene as a model substrate

  Yoshinori Ikenaka, Shouta M. M. Nakayama, Mami Oguri, Aksorn Saengtienchai, Hazuki Mizukawa, Jun Kobayashi, Wageh Sobhy Darwish, Mayumi Ishizuka

  ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 39 3 1148 - 1153 2015年05月 [査読有り][通常論文]
   

  Red gourami (Colisa labiosa) have previously been shown to have low levels of pyrene-metabolizing activity. In this study, other pharmacokinetic factors of pyrene in C. labiosa were compared to those in Japanese medaka (Oryzias latipes). Results indicated that the two species labiosa absorbed pyrene in similar amounts. However, excretion of pyrene metabolites from C. labiosa over an 8-day period was lower than those from O. latipes. These findings show that C. labiosa has low ability to metabolize pyrene and to excrete pyrene and its metabolites from the body, and is therefore considered an accumulator of these chemicals. C. labiosa has unique characteristics with regard to pyrene pharmacokinetics. Knowledge about interspecies differences in pharmacokinetics is crucial in determining the endangered species to xenobiotic exposure. (C) 2015 Elsevier B.V. All rights reserved.
• Partial cloning of CYP2C23a genes and hepatic protein expression in eight representative avian species

  K. P. Watanabe, Y. K. Kawai, S. M. M. Nakayama, Y. Ikenaka, H. Mizukawa, N. Takaesu, M. Ito, S. -I. Ikushiro, T. Sakaki, M. Ishizuka

  JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS 38 2 190 - 195 2015年04月 [査読有り][通常論文]
   

  Large interspecies differences in avian xenobiotic metabolism have been revealed by microsome-based studies, but specific enzyme isoforms in different bird species have not yet been compared. We have previously shown that CYP2C23 genes are the most induced CYP isoforms in chicken liver. In this study, we collected partial CYP2C23a gene sequences from eight avian species (ostrich, blue-eared pheasant, snowy owl, great-horned owl, Chilean flamingo, peregrin falcon, Humboldt penguin, and black-crowned night heron) selected to cover the whole avian lineage: Paleognathae, Galloanserae, and Neoaves. Genetic analysis showed that CYP2C23 genes of Galloanserae species (chicken and blue-eared pheasant) had unique characteristics. We found some duplicated genes (CYP2C23a and CYP2C23b) and two missing amino acid residues in Galloanserae compared to the other two lineages. The genes have lower homology than in other avian lineages, which suggests Galloanserae-specific rapid evolutionary changes. These genetic features suggested that the Galloanserae are not the most representative avian species, considering that the Neoaves comprise more than 95% of birds. Moreover, we succeeded in synthesizing an antipeptide polyclonal antibody against the region of CYP2C23 protein conserved in avians. However, comparative quantitation of CYP2C23 proteins in livers from six species showed that expression levels of these proteins differed no more than fourfold. Further study is needed to clarify the function of avian CYP2C23 proteins.
• Lead poisoning in children from townships in the vicinity of a lead-zinc mine in Kabwe, Zambia

  John Yabe, Shouta M. M. Nakayama, Yoshinori Ikenaka, Yared B. Yohannes, Nesta Bortey-Sam, Balazs Oroszlany, Kaampwe Muzandu, Kennedy Choongo, Abel Nketani Kabalo, John Ntapisha, Aaron Mweene, Takashi Umemura, Mayumi Ishizuka

  CHEMOSPHERE 119 941 - 947 2015年01月 [査読有り][通常論文]
   

  Childhood lead poisoning is a serious public health concern worldwide. Blood lead levels exceeding 5 mu g dL(-1) are considered elevated. In Kabwe, the capital of Zambia's Central Province, extensive Pb contamination of township soils in the vicinity of a Pb-Zn mine and posing serious health risk to children has been reported. We investigated BLLs in children under the age of 7 years in townships around the mine; where blood samples were collected and analyzed using an ICP-MS. All of the sampled children had BLLs exceeding 5 mu g dL(-1). Children in these areas could be at serious risk of Pb toxicity as 18% of the sampled children in Chowa, 57% (Kasanda) and 25% (Makululu) had BLLs exceeding 65 mu g dL(-1). Eight children had BLLs exceeding 150 mu g dL(-1) with the maximum being 427.8 mu g dL(-1). We recommend that medical intervention be commenced in the children with BLL exceeding 45 mu g dL(-1). (C) 2014 Elsevier Ltd. All rights reserved.
• Human health risks from metals and metalloid via consumption of food animals near gold mines in Tarkwa, Ghana: Estimation of the daily intakes and target hazard quotients (THQs)

  Nesta Bortey-Sam, Shouta M. M. Nakayama, Yoshinori Ikenaka, Osei Akoto, Elvis Baidoo, Yared Beyene Yohannes, Hazuki Mizukawa, Mayumi Ishizuka

  ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 111 160 - 167 2015年01月 [査読有り][通常論文]
   

  Heavy metal and metalloid contamination in food resulting from mining is of major concern due to the potential risk involved. Food consumption is the most likely route of human exposure to metals. This study was therefore to assess metals in different organs and different animal species near gold mines used for human consumption (free-range chicken, goat and sheep) in Tarkwa, Ghana, and to estimate the daily intake and health risk. The concentrations of Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Cd, and Pb were measured with an inductively coupled plasma-mass spectrometer and Hg analysis was done using the mercury analyzer. Principal component analysis of the results showed a clear separation between chicken, grouped on one side, and the ruminants clustered on another side in both offal and muscle. Interestingly, As, Cd, Hg, Mn and Pb made one cluster in the offal of chicken. Chicken muscle also showed similar distribution with As, Hg and Pb clustered together. The daily intake of metals (mu g/kg body weight/day) were in the following ranges; As [0.002 (kidneys of goat and sheep)-0.19 (chicken gizzard)], Cd [0.003 (chicken muscle)-0.55 (chicken liver)], Hg [0.002 (goat muscle)-0.29 (chicken liver)], Pb [0.01 (muscles and kidneys of goat and sheep)-0.96 (chicken gizzard)] and Mn [0.13 (goat kidney)-8.92 (sheep liver)]. From the results, daily intakes of As, Cd, Hg, Pb and Mn in these food animals were low compared to the provisional tolerable daily intake guidelines. The THQs although less than one, indicated that contributions of chicken gizzard and liver to toxic metal exposure in adults and especially children could be significant. (C) 2014 Published by Elsevier Inc.
• Occurrence, distribution, sources and toxic potential of polycyclic aromatic hydrocarbons (PAHs) in surface soils from the Kumasi Metropolis, Ghana

  Nesta Bortey-Sam, Yoshinori Ikenaka, Shouta M. M. Nakayama, Osei Akoto, Yared Beyene Yohannes, Elvis Baidoo, Hazuki Mizukawa, Mayumi Ishizuka

  SCIENCE OF THE TOTAL ENVIRONMENT 496 471 - 478 2014年10月 [査読有り][通常論文]
   

  As a developing country, the economic and population growth rates in Ghana over the past few years have seen a tremendous increase. The growing rate of industrialization is gradually leading to contamination and deterioration of the environment and pollution is likely to reach disturbing levels. Surface soil samples were collected randomly from 36 communities in the Kumasi Metropolis, Ghana, to determine the concentrations, distribution, sources and toxic potential of emission of polycyclic aromatic hydrocarbons (PAHs) since no such comprehensive study had been conducted. The mean concentration of total PAHs in the surface soils in each community ranged from 14.78 at Ahinsan to 2084 ng/g dry weight at Adum with an average of 442.5 +/- 527.2 ng/g dry weight. Diagnostic ratios and chemical mass balance models of the results showed that PAHs in surface soil samples from the study area were mainly from fuel combustion. Carcinogenic potency of PAH load from the city centre was approximately 150 times higher as compared to a pristine site, Kwame Nkrumah University of Science and Technology's Botanical Garden. BaP, a human carcinogen, contributed 70% of the total PAHs toxicity level from the city centre of Kumasi. (C) 2014 Elsevier B.V. All rights reserved.
• TCDD‑induced chick cardiotoxicity is abolished by a selective cyclooxygenase‑2 (COX‑2) inhibitor NS398.

  Fujisawa N, Nakayama SM, Ikenaka Y, Ishizuka M

  Archives of toxicology 88 9 1739 - 1748 2014年09月 [査読有り][通常論文]
   

  Halogenated aromatic hydrocarbons, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are known to cause severe heart defects in avian species. However, the mechanism of TCDD-induced chick cardiovascular toxicity is unclear. In this study, we investigated cyclooxygenase-2 (COX-2) as a possible mechanism of TCDD-induced cardiotoxicity. Fertile chicken eggs were injected with TCDD and a COX-2 selective inhibitor, NS398, and we investigated chick heart failure on day 10. We found that the chick heart to body weight ratio and atrial natriuretic factor mRNA expression were increased, but this increase was abolished with treatment of NS398. In addition, the morphological abnormality of an enlarged ventricle resulting from TCDD exposure was also abolished with co-treatment of TCDD and NS398. Our results suggested that TCDD-induced chick heart defects are mediated via the nongenomic pathway and that they do not require the genomic pathway.
• IDENTIFICATION OF INTERSPECIFIC DIFFERENCES IN PHASE II REACTIONS: DETERMINATION OF METABOLITES IN THE URINE OF 16 MAMMALIAN SPECIES EXPOSED TO ENVIRONMENTAL PYRENE

  Aksorn Saengtienchai, Yoshinori Ikenaka, Shouta M. M. Nakayama, Hazuki Mizukawa, Mayu Kakehi, Nesta Bortey-Sam, Wageh Sobhy Darwish, Toshio Tsubota, Masanori Terasaki, Amnart Poapolathep, Mayumi Ishizuka

  ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY 33 9 2062 - 2069 2014年09月 [査読有り][通常論文]
   

  Interspecific differences in xenobiotic metabolism are a key to determining relative sensitivities of animals to xenobiotics. However, information on domesticated livestock, companion animals, and captive and free-ranging wildlife is incomplete. The present study evaluated interspecific differences in phase II conjugation using pyrene as a nondestructive biomarker of polycyclic aromatic hydrocarbon (PAH) exposure. Polycyclic aromatic hydrocarbons and their metabolites have carcinogenic and endocrine-disrupting effects in humans and wildlife and can have serious consequences. The authors collected urine from 16 mammalian species and analyzed pyrene metabolites. Interspecific differences in urinary pyrene metabolites, especially in the concentration and composition of phase II conjugated metabolites, were apparent. Glucuronide conjugates are dominant metabolites in the urine of many species, including deer, cattle, pigs, horses, and humans. However, they could not be detected in ferret urine even though the gene for ferret Uridine 5'-diphospho-glucuronosyltransferase (UDP-glucuronosyltransferase, UGT) 1A6 is not a pseudogene. Sulfate conjugates were detected mainly in the urine of cats, ferrets, and rabbits. Interestingly, sulfate conjugates were detected in pig urine. Although pigs are known to have limited aryl sulfotransferase activity, the present study demonstrated that pig liver was active in 1-hydroxypyrene sulfation. The findings have some application for biomonitoring environmental pollution. (c) 2014 SETAC
• Organochlorine pesticides in bird species and their prey (fish) from the Ethiopian Rift Valley region, Ethiopia

  Yared Beyene Yohannes, Yoshinori Ikenaka, Shouta M. M. Nakayama, Mayumi Ishizuka

  ENVIRONMENTAL POLLUTION 192 121 - 128 2014年09月 [査読有り][通常論文]
   

  Organochlorine pesticides (OCPs) and stable isotopes were measured in muscle from 4 bird and 5 fish species from the Ethiopian Rift Valley region where DDT is used for malaria control and vast agricultural activities are carried out. We investigated the bioaccumulation of OCPs such as DDTs, HCHs, chlordanes, and heptachlors between the species, and examined the potential risk posed by these compounds for bird species. Significant differences in contaminant profiles and levels were observed within the species. Levels of total OCPs ranged from 3.7 to 148.7 mu g/g lipid in bird and 0.04 to 10.9 mu g/g lipid in fish species. DDTs were the predominant contaminant, and a positive relationship between delta N-15 and Sigma DDT concentrations was found. The main DDT metabolite, p,p'-DDE was the most abundant and significantly greater concentrations in bird species (up to 138.5 mu g/g lipid), which could have deleterious effects on survival and/or reproduction of birds. (C) 2014 Elsevier Ltd. All rights reserved.
• Apoptosis and gene expression in the developing mouse brain of fusarenon-X-treated pregnant mice.

  Sutjarit S, Nakayama SM, Ikenaka Y, Ishizuka M, Banlunara W, Rerkamnuaychoke W, Kumagai S, Poapolathep A

  Toxicology letters 229 1 292 - 302 1 2014年08月17日 [査読有り][通常論文]
   

  Fusarenon-X (FX), a type B trichothecene mycotoxin, is mainly produced by Fusarium crookwellense, which occurs naturally in agricultural commodities, such as wheat and barley. FX has been shown to exert a variety of toxic effects on multiple targets in vitro. However, the embryonic toxicity of FX in vivo remains unclear. In the present study, we investigated FX-induced apoptosis and the relationship between the genetic regulatory mechanisms and FX-induced apoptosis in the developing mouse brain of FX-treated pregnant mice. Pregnant mice were orally administered FX (3.5 mg/kg b.w.) and were assessed at 0, 12, 24 and 48 h after treatment (HAT). Apoptosis in the fetal brain was determined using hematoxylin and eosin staining, the TUNEL method, immunohistochemistry for PCNA and electron microscopy. Gene expressions were evaluated using microarray and real time-reverse transcription polymerase chain reaction (qRT-PCR). Histopathological changes showed that the number of apoptotic cells in the telencephalon of the mouse fetus peaked at 12 HAT and decreased at 24 and 48 HAT. FX induced the up-regulation of Bax, Trp53 and Casp9 and down-regulated Bcl2 but the expression levels of Fas and Casp8 mRNA remained unchanged. These data suggested that FX induces apoptosis in the developing mouse brain in FX-treated dams. Moreover, the genetic regulatory mechanisms of FX-induced apoptosis are regulated by Bax, Bcl2, Trp53 and Casp9 or can be defined via an intrinsic apoptotic pathway.
• Concentrations and human health risk assessment of organochlorine pesticides in edible fish species from a Rift Valley lake-Lake Ziway, Ethiopia

  Yared B. Yohannes, Yoshinori Ikenaka, Aksorn Saengtienchai, Kensuke P. Watanabe, Shouta M. M. Nakayam, Mayumi Ishizuka

  ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 106 95 - 101 2014年08月 [査読有り][通常論文]
   

  Fish consumption is known to have several health benefits for humans. However, the accumulation of organic pollutants, like organochlorine pesticides (OCPs) could pose health hazards. Thus, OCPs in edible fish species (Oreochromis niloticus, Tilapia zillii, Carassius spp., and Clarias gariepinus) from Lake Ziway, an Ethiopian Rift Valley Lake were investigated to assess the potential human health hazards of these contaminants. Dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexanes (HCHs), chlordanes, and heptachlors were observed with Sigma OCPs concentration ranging from 1.41 to 63.8 ng g(-1) ww. DDTs were the predominant contaminants (0.9 to 61.9 ng g(-1) ww), followed by HCHs. The predominance of DDTs may be attributed to their current use in vector control and contamination from past usage. The estimated daily intakes (EDIs) of OCPs from all fish species were much lower than the acceptable daily intakes (ADIs), indicating that consumption of fish is at little risk to human health at present. However, the cancer risk estimates in the area of concern and the hazard ratios (HRs) of HCHs, DDTs, and heptachlors exceeded the threshold value of one, indicating daily exposure to these compounds is a potential concern. This may result in a lifetime cancer risk greater than of I in 10(6). (C) 2014 Elsevier Inc. All rights reserved.
• Contamination status and possibility of toxic effects of co-planar polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and dichlorodiphenyltrichloroethane in large Japanese field mouse (Apodemus speciosus) collected from Hokkaido and Aomori

  Hazuki Mizukawa, Yoshinori Ikenaka, Shouta M. M. Nakayama, Kentaro Q. Sakamoto, Shoichi Fujita, Mayumi Ishizuka

  JAPANESE JOURNAL OF VETERINARY RESEARCH 62 3 107 - 115 2014年08月 [査読有り][通常論文]
   

  Contamination levels of coplanar polychlorinated biphenyls (Co-PCBs), polycyclic aromatic hydrocarbons (PAHs), and dichlorodiphenyltrichloroethane (DDTs) were measured in the entire body of the large Japanese field mouse (Apodemus speciosus) collected from Hokkaido (Ishikari and Rankoshi) and Aomori prefecture (Takko) in Japan. Higher concentrations of PCBs including Co-PCBs, were observed in the mice collected from Ishikari than those from Rankoshi. The concentration of PAHs in the soil from Ishikari was also higher than that in the other sampling sites. The findings suggest that Ishikari is the most polluted area, probably because of human activities, depending on the population distribution. However, the observed contaminant levels were extremely lower compared to those in previous studies. The ratio of testis weight to body weight (TW/BW) was the lowest in the mice collected from Ishikari, which is the area contaminated with PAHs and p,p'-dichlorodiphenyldichloroethylene (DDE). However, the serum testosterone levels of mice from the Ishikari area were higher than those from the non-contaminated other areas although no significant differences. Previous studies have shown that a low-level exposure to dioxin related compounds (DRCs) disturbances in sexual function, resulting in the production of testosterone. This study showed that POPs exposure is one of the possibility of the high testosterone concentration in the mice of the Ishikari area in addition to a cause of biological and environmental factors such as habitat density, age, temperatures and/or food riches.
• Contamination status and accumulation characteristics of metals and a metalloid in birds on Teuri Island, Hokkaido, Japan

  Chihiro Ishii, Yoshinori Ikenaka, Shouta M. M. Nakayama, Yuya Suzuki, Yutaka Watanuki, Yuji Watanabe, Yared Beyene Yohannes, Hazuki Mizukawa, Mayumi Ishizuka

  JAPANESE JOURNAL OF VETERINARY RESEARCH 62 3 143 - 149 2014年08月 [査読有り][通常論文]
   

  Teuri Island, Hokkaido in Japan is an important place for seabirds breeding. We measured the concentrations of heavy metals (Hg, Cd, Cr, Co, Ni, Cu, Zn, and Pb) and a metalloid (As) in rhinoceros auklet (Cerorhinca monocerata) (n = 7), thick-billed murre (Uria lomvia) (n = 2), spectacled guillemot (Cepphus carbo) (n = 6), slaty-backed gull (Larus schistisagus) (n = 15), jungle crow (Corvus macrorhynchos) (n = 3), Japanese anchovy (Engraulis japonica) (n = 6) and Atka mackerel (Pleurogrammus azonus) (n = 2). Spectacled guillemot had high As concentrations, with its source being their feeding habitat. Concentration of Hg in kidney of jungle crow was higher than other seabird species at Teuri.
• An Overview on Mycotoxin Contamination of Foods in Africa

  Wageh Sobhy Darwish, Yoshinori Ikenaka, Shouta M. M. Nakayama, Mayumi Ishizuka

  JOURNAL OF VETERINARY MEDICAL SCIENCE 76 6 789 - 797 2014年06月 [査読有り][通常論文]
   

  Mycotoxins are fungal secondary metabolites that contaminate various feedstuffs and agricultural crops. The contamination of food by mycotoxins can occur before production, during storage, processing, transportation or marketing of the food products. High temperature, moisture content and water activity are among the predisposing factors that facilitate the production of mycotoxins in food. Aflatoxins, ochratoxins, fumonisins, deoxynivalenol and zearalenone are all considered the major mycotoxins produced in food and feedstuffs. In Africa, mycotoxin contamination is considered to be a major problem with implications that affect human and animal health and economy. Aflatoxin-related hepatic diseases are reported in many African countries. Ochratoxin and fumonisin toxicity in humans and animals is widespread in Africa. The available, updated information on the incidence of mycotoxin contamination, decontamination and its public health importance in Africa is lacking. The aim of this review is to highlight, update and discuss the available information on the incidence of mycotoxins in African countries. The public health implications and the recommended strategies for control of mycotoxins in food and agricultural crops are also discussed.
• The Effect of Copper on the mRNA Expression Profile of Xenobiotic-Metabolizing Enzymes in Cultured Rat H4-II-E Cells

  Wageh Sobhy Darwish, Yoshinori Ikenaka, Shouta Nakayama, Mayumi Ishizuka

  BIOLOGICAL TRACE ELEMENT RESEARCH 158 2 243 - 248 2014年05月 [査読有り][通常論文]
   

  Copper (Cu2+) is an essential element that plays important roles in physiological functions of the body. However, high Cu2+ levels can have toxic implications. This study aims to investigate the constitutive response to Cu2+ exposure of xenobiotic-metabolizing enzymes in cultured rat liver (H4-II-E) cell lines. Rat cells were exposed to copper sulfate (0-500 mu M) for 24 h. The effects of Cu2+ on the messenger RNA (mRNA) expressions of phase I and II enzymes and regulatory elements were examined using real-time PCR. Metallothionein mRNA expression was induced in a dose-dependent manner after treatment with Cu2+. mRNA expressions of phase I enzymes such as cytochrome P450 1A1 and 1A2 (CYP1A1 and CYP1A2) were slightly induced after exposure to low concentrations of Cu2+; however, CYP1A1 and CYP1A2 mRNA expressions were significantly downregulated at higher Cu2+ concentrations. These effects corresponded with expression of aryl hydrocarbon receptor mRNA. The mRNA expressions of phase II enzymes were reduced upon exposure to Cu2+. In conclusion, phase I and II enzyme expressions were significantly modulated upon Cu2+ exposure. These results indicated that Cu2+ exposure had toxicological implications for cultured H4-II-E cells.
• Heavy metal contamination of soil and sediment in Zambia

  Yoshinori Ikenaka, Shouta M.M. Nakayama, Kaampwe Muzandu, Kennedy Choongo, Hiroki Teraoka, Naoharu Mizuno, Mayumi Ishizuka

  Heavy Metal Contamination of Water and Soil: Analysis, Assessment, and Remediation Strategies 109 - 128 2014年01月01日 

  Africa is a continent located in the southern hemisphere and known for its rich diversity of wildlife including birds, amphibians, reptiles and large mammals. However, in recent years, there have been concerns about significant environmental problems caused by the mining of rare and major metals and metallurgical activities in African countries by domestic and foreign corporations (Oelofse, 2008). Environmental pollution due to the rapid progress of economic development in Africa can cause various problems and heavy metals are some of the major contaminants in these countries (Akiwumi and Butler, 2008; Norman et al., 2007; Rashad and Barsoum, 2006). Humans and wildlife can be exposed to heavy metals by drinking water and inhaling air or soil contaminated by mining activities and the metal industry (Nakayama et al., 2010).
• SPECIES DIFFERENCE OF WARFARIN SENSITIVITY AMONG BIRDS CAN BE EXPLAINED BY THE TWO ENZYMES, CYTOCHROME P450 AND VITAMIN K EPOXIDE REDUCTASE

  Kensuke P. Watanabe, Yusuke K. Kawai, Minami Kawata, Shouta M. M. Nakayama, Yoshinori Ikenaka, Mayumi Ishizuka

  DRUG METABOLISM REVIEWS 45 92 - 92 2014年01月 [査読有り][通常論文]
  
• Occurrence, distribution, and ecological risk assessment of DDTs and heavy metals in surface sediments from Lake Awassa-Ethiopian Rift Valley Lake

  Yared Beyene Yohannes, Yoshinori Ikenaka, Aksorn Saengtienchai, Kensuke P. Watanabe, Shouta M. M. Nakayama, Mayumi Ishizuka

  ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH 20 12 8663 - 8671 2013年12月 [査読有り][通常論文]
   

  Dichlorodiphenyltrichloroethanes (DDTs) and heavy metals are ubiquitous contaminants with high bioaccumulation and persistence in the environment, which can have adverse effects on humans and animals. Although applications of DDTs have been banned in many countries, developing countries like Ethiopia are still using these for agricultural and medicinal purposes. In addition, heavy metals are naturally present in the aquatic environment and distributed globally. In this study, the occurrence, distribution, and ecological risk of DDTs and heavy metals in surface sediments from one of the Ethiopian rift valley lakes were studied. Twenty-five surface sediment samples from Lake Awassa, Ethiopia were collected and analyzed for DDTs and heavy metals. Results showed that concentrations of total DDTs ranged from 3.64 to 40.2 ng/g dry weight. High levels of DDTs were observed in the vicinity of inflow river side and coastal areas with agricultural activities. The heavy metals content were followed the order Zn > Ni > Pb > Cu > Cr > Co > As > Cd > Hg. Correlation analysis and principal components analysis demonstrated that heavy metals were originated from both natural and anthropogenic inputs. The levels of DDE and DDD in surface sediments exceeded the sediment quality guideline values, indicating that adverse effects may occur to the lake. A method based on toxic-response factor for heavy metals revealed that the calculated potential ecological risk indices showed low ecological risk for the water body.
• Dioxin Sensitivity-Related Two Critical Amino Acids of Arylhydrocarbon Receptor May Not Correlate with the Taxonomy or Phylogeny in Avian Species

  Nozomi Fujisawa, Yusuke K. Kawai, Shouta M. M. Nakayama, Yoshinori Ikenaka, Hideaki Yamamoto, Mayumi Ishizuka

  JOURNAL OF VETERINARY MEDICAL SCIENCE 75 12 1577 - 1583 2013年12月 [査読有り][通常論文]
   

  There are two arylhydrocarbon receptor (AhR) isoforms in birds, AhR1 and AhR2. The varying sensitivity of AhR is reported to be related to two critical amino acids at positions 325 and 381 in the AhR1 ligand-binding domain. In this study, seven avian species whose in vivo dioxin sensitivity was known, and 13 species with no data regarding their in vivo dioxin sensitivity were examined. The two critical amino acids in the ligand-binding domain were investigated in avian species, and the results were compared with the taxonomy or phylogenetic trees for the bird AhR proteins. We found that the two critical amino acids did not correlate with the taxonomy or phylogeny of these proteins, suggesting that dioxin sensitivity was independent of taxonomy.
• Repeated Treatment with Furazolidone Induces Multiple Cytochrome P450-Related Activities in Chicken Liver, but Not in Rat Liver

  Nobuo Sasaki, Tomoyuki Matumoto, Yoshinori Ikenaka, Shouta M. M. Nakayama, Mayumi Ishizuka, Akio Kazusaka, Shoichi Fujita

  JOURNAL OF VETERINARY MEDICAL SCIENCE 75 11 1497 - 1502 2013年11月 [査読有り][通常論文]
   

  The nitrofuran antimicrobial agent, furazolidone (FZ), is still used in veterinary medicine in some countries in the Middle and Far Eastern countries. The present study aimed to investigate the effects of successive bolus doses of FZ and its metabolite 3-amino-2-oxazolidinone (AOZ) on cytochrome P450 (CYP)-related activities in the livers of rats and chickens. Female Wistar rats and white Leghorn chickens were orally administered FZ once a day for 4 consecutive days. FZ-treated chickens showed an increase in multiple CYP-related activities, however, rats treated with FZ did not show these changes. In chickens, treatment with FZ also induced production of microsomal CYP2C6-like apoprotein. The present study demonstrated that FZ caused a multiple-type induction of CYP-related activities in chickens, but not in rats.
• Characterization of phase-II conjugation reaction of polycyclic aromatic hydrocarbons in fish species: unique pyrene metabolism and species specificity observed in fish species.

  Yoshinori Ikenaka, Mami Oguri, Aksorn Saengtienchai, Shouta M M Nakayama, Shigeho Ijiri, Mayumi Ishizuka

  Environmental toxicology and pharmacology 36 2 567 - 578 2013年09月 [査読有り][通常論文]
   

  Metabolic activity, particularly conjugation, was examined in fish by analyzing pyrene (a four-ring, polycyclic aromatic hydrocarbon) metabolites using high-performance liquid chromatography (HPLC) with fluorescence detector (FD), a mass spectrometry (MS) system, and kinetic analysis of conjugation enzymes. Fourteen fresh water fish species, including Danio rerio and Orizias latipes, were exposed to aqueous pyrene, and the resulting metabolites were collected. Identification of pyrene metabolites by HPLC/FD and ion-trap MS indicated that the major metabolites were pyrene glucuronide and pyrene sulfate in all 14 species. Differences were observed in pyrene glucuronide:pyrene sulfate ratio and in the total amount of pyrene conjugates excreted between fish species. Furthermore, a correlation was found between the amount of pyrene glucuronide present and the total amount of the pyrene metabolite eliminated. Kinetic analysis of conjugation by hepatic microsomes in vitro indicated that the differences in excreted metabolites reflected the differences in enzymatic activities.
• Accumulation and biological effects of metals in wild rats in mining areas of Zambia

  Shouta M. M. Nakayama, Yoshinori Ikenaka, Kyohei Hamada, Kaampwe Muzandu, Kennedy Choongo, John Yabe, Takashi Umemura, Mayumi Ishizuka

  ENVIRONMENTAL MONITORING AND ASSESSMENT 185 6 4907 - 4918 2013年06月 [査読有り][通常論文]
   

  The lead-zinc (Pb-Zn) mine in Kabwe City and the copper-cobalt (Cu-Co) mine in the Copperbelt Province are major mining areas in Zambia. To examine the effects of metal pollution on wildlife, wild black rats (Rattus rattus and Rattus tanezumi) were captured in Kabwe and Chingola (in the Copperbelt Province), and in Lusaka (a noncontaminated site). Wild black rats in Kabwe accumulated significantly higher concentrations of Pb and Cd in various organs than rats from Lusaka. In Chingola, significantly higher concentrations of Cu, Co, Pb, and Cd were accumulated in wild black rats than in rats from Lusaka. These results were in accordance with metal accumulation patterns in soil. From toxicological aspects, concentrations of Pb and Cd in rats were generally low. However, metallothionein-1 (MT-1) and metallothionein-2 (MT-2) mRNA expression levels in wild black rats from Kabwe were significantly higher than those in rats from Lusaka. A generalized linear model (GLM) showed that concentrations of Zn and Cu had positive effects on the MT-1 and MT-2 mRNA expression. These results suggest that wild black rats in Zambian mining sites were exposed to metals that accumulated in their organs, causing biological responses such as MT mRNA induction. GLM indicated that heme oxygenase-1 (HO-1) mRNA expression could be a marker for Cr exposure.
• Organochlorine pesticides and heavy metals in fish from Lake Awassa, Ethiopia: Insights from stable isotope analysis

  Yared Beyene Yohannes, Yoshinori Ikenaka, Shouta M. M. Nakayama, Aksorn Saengtienchai, Kensuke Watanabe, Mayumi Ishizuka

  CHEMOSPHERE 91 6 857 - 863 2013年05月 [査読有り][通常論文]
   

  The levels and bioaccumulation of organochlorine pesticides (OCPs) and heavy metals were studied in muscle and liver of three fish species, with two trophic levels, from Lake Awassa, Ethiopia. DDTs were the predominant organic pollutant in all species with a maximum level of 73.28 ng g(-1) wet weight (ww). p,p'-DDE was the predominate congener and showed a significant (p <0.001) relationship with delta N-15, which indicates that DDTs could biomagnified in the food web of the lake. Generally, high levels of heavy metals (Cd, Co, Cr, Cu, Ni, Pb, Zn and Hg) were found in liver samples as compared to muscles. The levels of Cd, Co, Cu, Ni, and Pb in liver samples showed negative correlation with delta N-15. They were found markedly higher in the lower trophic level fish species (p < 0.05) that indicates biodilution whereas; Zn level showed positive correlation with delta N-15. (C) 2013 Elsevier Ltd. All rights reserved.
• Antibiotic residues in food: the African scenario

  Wageh Sobhy Darwish, Elsaid A. Eldaly, Mohamed Tharwat E-Abbasy, Yoshinori Ikenaka, Shouta Nakayama, Mayumi Ishizuka

  JAPANESE JOURNAL OF VETERINARY RESEARCH 61 Supplement S13 - S22 2013年02月 [査読有り][通常論文]
   

  Antibiotics are substances either produced naturally by living organisms or synthetically in the laboratory, and they are able to kill or inhibit the growth of microorganisms. Antibiotics are also used as feed additives for the purpose of livestock health maintenance. Antibiotic residues in feedstuffs are currently a problem of some magnitude in different parts of the world, particularly due to associated public health concerns that include hypersensitivity reactions, antibiotic resistance, toxicity, teratogenicity, and carcinogenicity. In Africa, as in other parts of the world, antibiotic residues in animal-derived foods have been extensively recorded in many African countries; these residues have exceeded the WHO maximum residue levels in many cases. It has been reported that tetracyclines are the most predominantly prescribed antibiotics in Africa, and of all antibiotic-associated residues they represent 41% of cases, followed by beta-lactams at 18%. Great care should be taken to monitor antibiotic cessation periods before the release of animal-derived foods for human consumption. In addition, strict legislation should be implemented in order to minimize the abuse of antibiotics.
• Distribution of metals in organs of Clarias gariepinus, Heterobranchus bidorsalis, and Chrysichthys nigrodigitatus from the Offin River at Dunkwa-on-Offin, Ghana.

  Jemima T Marfo, Osei Akoto, Shouta M M Nakayama, Elvis Baidoo, Yoshinori Ikenaka, Mayumi Ishizuka

  The Japanese journal of veterinary research 61 Suppl S69-71 - 71 2013年02月 [査読有り][通常論文]
   

  All heavy metals are potentially harmful to most organisms at some level of exposure and absorption. Concentrations of Co, Cr, Cu, Ni, Zn, Hg, Cd, As, and Pb were determined by atomic absorption spectrophotometry (AAS) in three fish species (C. gariepinus, C. nigrodigitatus, and H. bidorsalis) from the Offin River in Dunkwa township, Ghana. In the fish species, gills, livers, and muscles were analyzed. The metal that recorded the highest concentration was Zn, which was highly accumulated in the liver of C. gariepinus, but had the lowest concentration in the muscles of C. nigrodigitatus.
• Determination of benzo[a]pyrene levels in ambient air and the source of polycyclic aromatic hydrocarbons using a diagnostic ratio method in Ghana

  Nesta Bortey-Sam, Osei Akoto, Yoshinori Ikenaka, Shouta M. M. Nakayama, Mayumi Ishizuka

  JAPANESE JOURNAL OF VETERINARY RESEARCH 61 S72 - S74 2013年02月 [査読有り][通常論文]
   

  Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants produced from incomplete combustion of fuel or vegetation fires. Their presence in air deserves attention because they can produce carcinogenic and mutagenic effects. As an industrialized and economically significant city in Ghana, Kumasi has been subject to heavy anthropogenic influences due to rapid economic development and urbanization leading to a greater fuel combustion rate. Airborne particulate samples were collected on filters using a Sibata air sampler and analyzed by gas chromatography-mass spectrometry (GC-MS). Our results indicated that air from the city center can be classified as highly polluted with benzo[a] pyrene (B[a]P). The diagnostic ratios of the results showed that PAHs in the air samples were mainly from fuel combustion.
• Heavy metal pollution in Japanese seabirds

  Chihiro Ishii, Yoshinori Ikenaka, Shouta M. M. Nakayama, Yuya Suzuki, Yutaka Watanuki, Yuji Watanabe, Masa-aki Fukuwaka, Yared B. Yohannes, Yusuke K. Kawai, Mayumi Ishizuka

  JAPANESE JOURNAL OF VETERINARY RESEARCH 61 S75 - S76 2013年02月 [査読有り][通常論文]
   

  It is reported that seabirds accumulate high levels of metals, prompting concerns regarding poisoning. The present study investigated the accumulation patterns of metals in tissues among four species of seabirds (Fratercula corniculata, Uria lomvia, Puffinus tenuirostris, and Fulmarus glacialis). Furthermore, we focused on Slaty-backed Gulls, which accumulated high levels of cadmium and mercury, and compared the areal differences. Geographic variation of metal levels could also contribute to differences in metal accumulation levels in these bird species. Therefore, the concentrations of metals in seabirds are considered to reflect their habitat. There are differences in the accumulation pattern among the seabird species. The high accumulation of metals could affect seabirds even if they do not show any symptoms.
• Metabolism of pyrene, a polycyclic aromatic hydrocarbon in freshwater turtles

  Balazs Oroszlany, Yoshinori Ikenaka, Aksorn Saengtiengchan, Mami Oguri, Shouta M. M. Nakayama, Mayumi Ishizuka

  JAPANESE JOURNAL OF VETERINARY RESEARCH 61 S77 - S78 2013年02月 [査読有り][通常論文]
   

  Reptile population decrease is an alarming trend all around the world. Yet little is known about the role of xenobiotics in this decrease. In this study, we investigated the metabolism of pyrene in three freshwater turtle species (Red-EARED sliders (Trachemys scripta elegans), Chinese pond turtles (Mauremys reevesii) and Chinese softshell turtles (Pelodiscus sinensis). Compared to other vertebrates, all turtles showed an unique metabolite distribution, pyrene-1-sulfate being the main metabolite. The observed low phase II enzyme metabolic rates raises the question of the effect of long-time exposure.
• Metal contaminated soil from mining area caused metal accumulation and biological responses in rats

  Shouta M. M. Nakayama, Yoshinori Ikenaka, Kaampwe Muzandu, Kennedy Choongo, John Yabe, Takashi Umemura, Mayumi Ishizuka

  JAPANESE JOURNAL OF VETERINARY RESEARCH 61 S79 - S81 2013年02月 [査読有り][通常論文]
   

  In order to assess the effects of metal contamination on wildlife, we collected wild black rats (Rattus sp.) from mining areas (Kabwe and Chingola) and a control area (Lusaka) in Zambia and compared metal and metallothionein (MT) levels in their tissues. Furthermore, we exposed metal-contaminated soil from Kabwe to laboratory Wistar rats (Rattus norvegicus) for one year in order to determine the accumulation factors and effects of metals caused by soil exposure. Results of both the field and laboratory studies suggested that metal-contaminated soil caused accumulation and biological responses such as elevation of MT-2 mRNA expression levels in rats.
• In vitro diazepam metabolism in horses

  Aki Hayami, Wageh Sobhy Darwish, Yoshinori Ikenaka, Shouta M. M. Nakayama, Mayumi Ishizuka

  JAPANESE JOURNAL OF VETERINARY RESEARCH 61 S82 - S84 2013年02月 [査読有り][通常論文]
   

  There is little information about drug metabolism and pharmacokinetics in horses. Therefore, it is necessary to characterize the profiles of drug metabolites for the safe use of drugs. In this study, we focused on cytochrome P450 enzymes (CYPs), which represent an important enzyme group to determine pharmacological effects of drugs. We chose diazepam as the drug of choice for this study. The aim of this study was to elucidate the metabolic pathway of diazepam in horses in comparison with rats, and to clarify CYP subfamilies responsible for diazepam metabolism in horses. Our results showed temazepam was the major diazepam metabolite produced from microsomal reactions in horse liver, but horses produced drastically less p-hydroxydiazepam as compared with rats. Furthermore, CYP3A was a major contributor from the CYP subfamily of temazepam production.
• Geographic information system-based source estimation of copper pollution in Lake Itezhi-tezhi and metal-accumulation profiles in Oreochromis spp. from both field and laboratory studies.

  Shouta M M Nakayama, Yoshinori Ikenaka, Kaampwe Muzandu, Kennedy Choongo, John Yabe, Taro Muroya, Shigeho Ijiri, Masao Minagawa, Takashi Umemura, Mayumi Ishizuka

  Archives of environmental contamination and toxicology 64 1 119 - 29 2013年01月 [査読有り][通常論文]
   

  The Copperbelt region, upstream of the Kafue River, including Lake Itezhi-tezhi (ITT), in Zambia has extensive copper (Cu) mines. In our field study, geographic information system analysis in lake sediment indicated that the northern part of the lake, i.e., the Copperbelt region, could be the source of Cu pollution. Concentrations of Cu in stomach contents between fish species were not significantly different. However, Oreochromis spp. liver showed significantly greater Cu concentrations than those in other fish species. Log liver [Cu], standard length, and nitrogen stable isotope ratio were positively correlated only in Oreochromis spp. In the laboratory study, O. niloticus and O. latipes were exposed to Cu for 4 days, and recovery phases ≤ 28 days were examined. O. niloticus showed significantly greater concentrations of Cu compared with O. latipes at all sampling points. Significantly greater concentrations of Hg in Schilbe intermedius liver than for other fish species were observed, whereas O. macrochir showed significantly greater concentrations of cadmium. In conclusion, the northern part of the lake could be the source of Cu pollution in Lake ITT. Diet may not be the reason for high Cu accumulation in Oreochromis spp. Results from both field and laboratory studies imply that Oreochromis spp. contain high concentrations of Cu under normal physiological conditions.
• Metal distribution in tissues of free-range chickens near a lead-zinc mine in Kabwe, Zambia

  John Yabe, Shouta M. M. Nakayama, Yoshinori Ikenaka, Kaampwe Muzandu, Kennedy Choongo, Geoffrey Mainda, Matthew Kabeta, Mayumi Ishizuka, Takashi Umemura

  ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY 32 1 189 - 192 2013年01月 [査読有り][通常論文]
   

  Concentrations of Pb, Cd, and other metals in tissues of 17 free-range and 32 commercial broiler chickens from the Kabwe mining town in Zambia were determined. Mean concentrations of Pb and Cd exceeded maximum levels for human consumption in some organs including muscle (Pb only) in free-range chickens, in contrast to low levels in broiler chickens. Human consumers in Kabwe could be exposed to Pb and Cd in free-range chickens. Environ. Toxicol. Chem. 2013;32:189192. (c) 2012 SETAC
• Accumulation of Metals in the Liver and Kidneys of Cattle from Agricultural Areas in Lusaka, Zambia

  John Yabe, Shouta M. M. Nakayama, Yoshinori Ikenaka, Kaampwe Muzandu, Mayumi Ishizuka, Takashi Umemura

  JOURNAL OF VETERINARY MEDICAL SCIENCE 74 10 1345 - 1347 2012年10月 [査読有り][通常論文]
   

  Intensive agricultural practices are recognized as significant sources of metal pollution in soils and pasture. This study investigated metal contamination in cattle offal from an agricultural area in Zambia, where inorganic fertilizers, agricultural lime, and pesticides are routinely applied. The highest median values (mg/kg, wet weight) of Cu (40.9), Zn (35.2), Cr (1.35) and Ni (0.594) were recorded in the liver, whereas the highest median values of Pb (0.061) and Cd (0.049) were found in kidneys. Maximum levels of Hg, As and Co were under 0.2 mg/kg in both organs. Pb and Cd did not exceed the benchmark values in cattle offal for human consumption and did not pose immediate health risks. Concentrations of Ni and Cr could present a public health concern. Monitoring of metal accumulations in offal of cattle, not only from well-known polluted environments but also agricultural areas, should be done regularly for the health of human consumers.
• EFFECTS OF ENVIRONMENTAL LEAD CONTAMINATION ON CATTLE IN A LEAD/ZINC MINING AREA: CHANGES IN CATTLE IMMUNE SYSTEMS ON EXPOSURE TO LEAD IN VIVO AND IN VITRO

  Yoshinori Ikenaka, Shouta M. M. Nakayama, Taro Muroya, John Yabe, Satoru Konnai, Wageh Sobhy Darwish, Kaampwe Muzandu, Kennedy Choongo, Geoffrey Mainda, Hiroki Teraoka, Takashi Umemura, Mayumi Ishizuka

  ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY 31 10 2300 - 2305 2012年10月 [査読有り][通常論文]
   

  The Republic of Zambia is rich in mineral resources, such as zinc (Zn) and lead (Pb), and mining is a key industry in Zambia. A previous study of Pb pollution in Kabwe, one of the main mining areas, found that soil was contaminated with high levels of toxic metals over a substantial area. In the present study, the authors focus on toxic metal pollution in cattle, one of the most important domestic animals in Zambia. Blood samples from cattle in Kabwe and a control area (Lusaka) were tested for toxic metal content. They also measured mRNA expression of metal-responsive proteins and cytokines in white blood cells using real-time reverse transcriptase polymerase chain reaction. In the present in vitro study, The authors cultured peripheral blood mononuclear cells (PBMCs) from cattle, exposing them to Pb acetate for 24?h and analyzing mRNA expression of metal-responsive proteins and selected cytokines. Lead concentrations in cattle blood from Kabwe were significantly greater than those from Lusaka, as were the mRNA expressions of metallothionein-2 (MT-2), tumor necrosis factor-a (TNF-a), interferon-? (IFN-?), interleukin-1 beta (IL-1 beta), IL-6, and inducible nitric oxide synthase (iNOS). The present in vitro study demonstrated that Pb exposure led to an increase in the expressions of MT-2, TNF-a, IL-1 beta, and iNOS, similar to those found in vivo. These results indicate the possibility of immune system modulations in cattle from the Kabwe area. Environ. Toxicol. Chem. 2012; 31: 23002305. (c) 2012 SETAC
• The nucleotide sequence of metallothioneins (MT) in liver of the Kafue lechwe (Kobus leche kafuensis) and their potential as biomarkers of heavy metal pollution of the Kafue River

  Ethel M'kandawire, Michelo Syakalima, Kaampwe Muzandu, Girja Pandey, Martin Simuunza, Shouta M. M. Nakayama, Yusuke K. Kawai, Yoshinori Ikenaka, Mayumi Ishizuka

  GENE 506 2 310 - 316 2012年09月 [査読有り][通常論文]
   

  The study determined heavy metal concentrations and MT1 nucleotide sequence [phylogeny] in liver of the Kafue lechwe. Applicability of MT1 as a biomarker of pollution was assessed. cDNA-encoding sequences for lechwe MT1 were amplified by RT-PCR to characterize the sequence of MT1 which was subjected to BLAST searching at NCBI. Phylogenetic relationships were based on pairwise matrix of sequence divergences calculated by Clustal W. Phylogenetic tree was constructed by NJ method using PHILLIP program. Metals were extracted by acid digestion and concentrations of Cr, Co, Cu, Zn, Cd, Pb, and Ni were determined using an AAS. MT1 mRNA expression levels were measured by quantitative comparative real-time RT-PCR. Lechwe MT1 has a length of 183 bp, which encode for MT1 proteins of 61AA, which include 20 cysteines. Nucleotide sequence of lechwe MT1 showed identity with sheep MT (97%) and cattle MT1E (97%). Phylogenetic tree revealed that lechwe MT1 was clustered with sheep MT and cattle MT1E. Cu and Ni concentrations and MT1 mRNA expression levels of lechwe from Blue Lagoon were significantly higher than those from Lochinvar (p<0.05). Concentrations of Cd and Cu, Co and Cu, Co and Pb, Ni and Cu, and Ni and Cr were positively correlated. Spearman's rank correlations also showed positive correlations between Cu and Co concentrations and MT mRNA expression. PCA further suggested that MT mRNA expression was related to Zn and Cd concentrations. Hepatic MT1 mRNA expression in lechwe can be used as biomarker of heavy metal pollution. (C) 2012 Elsevier B.V. All rights reserved.
• Metal and metalloid levels and bio-accumulation characteristics in soil, sediment, land plants and hippopotami (Hippopotamus amphibius L) from the South Luangwa National Park, Zambia

  Shouta M. M. Nakayama, Yoshinori Ikenaka, Kaampwe Muzandu, Kennedy Choongo, Ethel M'kandawire, Jun Yasuda, Mayumi Ishizuka

  ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 80 333 - 338 2012年06月 [査読有り][通常論文]
   

  Hippopotami (Hippopotamus amphibius L) are large semi-aquatic mammals that can be exposed to metals and metalloid from both terrestrial and aquatic environments. Therefore, knowledge of metal and metalloid accumulation characteristics in hippopotami living in the national park is important from ecotoxicological point of view. Levels of toxic metals (Cd, Pb and Hg) and metalloid (As) in hippopotami liver from the South Luangwa National Park in Zambia were far lower compared to the established values of toxic levels in cattle. No temporal variations of metal levels in hippopotami were observed, probably because of good management condition and the lack of anthropogenic activities around the national park. However, hippopotami liver accumulated significantly higher concentrations of Hg compared to soil, sediment and their food (plants), most likely due to a process of biomagnification throughout a trophic chain. Moreover, hippopotami liver and land plants showed significantly higher Cd levels than those of soil. These results strongly suggest that hippopotami liver accumulate higher levels of these metals if surrounding environment is contaminated. Levels of Cr and Ni in hippopotami liver were higher compared to other toxic metals. Since this is the first report to show the Cr and Ni levels and bio-accumulation characteristics of Hg and Cd in hippopotami, we concluded that continuous monitoring and evaluation of toxic effects of these metals on hippopotami should be conducted. (C) 2012 Elsevier Inc. All rights reserved.
• Phase-II conjugation ability for PAH metabolism in amphibians: Characteristics and inter-species differences

  Haruki Ueda, Yoshinori Ikenaka, Shouta M. M. Nakayama, Tomoko Tanaka-Ueno, Mayumi Ishizuka

  AQUATIC TOXICOLOGY 105 3-4 337 - 343 2011年10月 [査読有り][通常論文]
   

  The present study examines amphibian metabolic activity - particularly conjugation - by analysis of pyrene (a four ring, polycyclic aromatic hydrocarbon) metabolites using high-performance liquid chromatography (HPLC) with fluorescence detector (FD), a mass spectrometry detector (MS) system and kinetic analysis of conjugation enzymes. Six amphibian species were exposed to pyrene (dissolved in water): African claw frog (Xenopus laevis); Tago's brown frog (Rana tagoi); Montane brown frog (Rana ornativentris); Wrinkled frog (Rana rugosa); Japanese newt (Cynops pyrrhogaster); and Clouded salamander (Hynobius nebulosus); plus one fish species, medaka (Oryzias latipes); and a fresh water snail (Clithon retropictus), and the resultant metabolites were collected. Identification of pyrene metabolites by HPLC and ion-trap MS system indicated that medaka mainly excreted pyrene-1-glucuronide (PYOG), while pyrene-1 -sulfate (PYOS) was the main metabolite in all amphibian species. Pyrene metabolites in amphibians were different from those in invertebrate fresh water snails. Inter-species differences were also observed in pyrene metabolism among amphibians. Metabolite analysis showed that frogs relied more strongly on sulfate conjugation than did Japanese newts and clouded salamanders. Furthermore, urodelan amphibians, newts and salamanders, excreted glucose conjugates of pyrene that were not detected in the anuran amphibians. Kinetic analysis of conjugation by hepatic microsomes and cytosols indicated that differences in excreted metabolites reflected differences in enzymatic activities. Furthermore, pyrenediol (PYDOH) glucoside sulfate was detected in the Japanese newt sample. This novel metabolite has not been reported previously to this report, in which we have identified unique characteristics of amphibians in phase II pyrene metabolism. (C) 2011 Elsevier B.V. All rights reserved.
• UPTAKE OF LEAD, CADMIUM, AND OTHER METALS IN THE LIVER AND KIDNEYS OF CATTLE NEAR A LEAD-ZINC MINE IN KABWE, ZAMBIA

  John Yabe, Shouta M. M. Nakayama, Yoshinori Ikenaka, Kaampwe Muzandu, Mayumi Ishizuka, Takashi Umemura

  ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY 30 8 1892 - 1897 2011年08月 [査読有り][通常論文]
   

  Concentrations of lead, cadmium, and other metals in the liver and kidneys of cattle near a lead-zinc mine in Kabwe (Zambia), which is ranked among the 10 worst polluted places on earth, were compared with other Zambian towns. Metal concentrations were measured in the liver and kidneys of 51 cattle from Kabwe and other Zambian towns. The maximum metal concentrations, expressed in mg/kg and dry weight, in the liver or kidneys were 398.4 (Cu), 252.6 (Zn), 77.81 (Cr), 19.37 (Cd), 7.57 (Ni), 1.8 (Pb), 1.04 (Co), 0.112 (Hg), and 0.05 (As). Concentrations of Pb and Cd in Kabwe cattle were higher than levels in other Zambian towns. The mean concentration of Cd exceeded benchmark values in offal destined for human consumption. Levels of Ni and Cr may also pose public health concerns. Concentrations of Pb and Cr, Pb and Cu, Cd and Zn, Cd and Hg, Zn and Cu, Cu and Co, as well as Co and Ni were positively correlated. The present study also highlighted the dangers of exposure of animals and humans to a mixture of toxic metals. Environ. Toxicol. Chem. 2011;30:1892-1897. (C) 2011 SETAC
• Metal and metalloid contamination in roadside soil and wild rats around a Pb-Zn mine in Kabwe, Zambia

  Shouta M. M. Nakayama, Yoshinori Ikenaka, Kyohei Hamada, Kaampwe Muzandu, Kennedy Choongo, Hiroki Teraoka, Naoharu Mizuno, Mayumi Ishizuka

  ENVIRONMENTAL POLLUTION 159 1 175 - 181 2011年01月 [査読有り][通常論文]
   

  Metal (Cr, Co, Cu, Zn, Cd, Pb, Ni) and metalloid (As) accumulation was studied in roadside soil and wild rat (Rattus sp.) samples from near a Pb Zn mine (Kabwe, Zambia) and the capital city of Zambia (Lusaka). The concentrations of the seven metals and As in the soil samples and Pb in the rat tissue samples were quantified using atomic absorption spectroscopy. The concentrations of Pb, Zn, Cu, Cd, and As in Kabwe soil were much higher than benchmark values. Geographic Information System analysis indicated the source of metal pollution was mining and smelting activity. Interestingly, the area south of the mine was more highly contaminated even though the prevailing wind flow was westward. Wild rats from Kabwe had much higher tissue concentrations of Pb than those from Lusaka. Their body weight and renal Pb levels were negatively correlated, which suggests that mining activity might affect terrestrial animals in Kabwe. (C) 2010 Published by Elsevier Ltd.
• Heavy Metal Accumulation in Lake Sediments, Fish (Oreochromis niloticus and Serranochromis thumbergi), and Crayfish (Cherax quadricarinatus) in Lake Itezhi-tezhi and Lake Kariba, Zambia

  Shouta M. M. Nakayama, Yoshinori Ikenaka, Kaampwe Muzandu, Kennedy Choongo, Balazs Oroszlany, Hiroki Teraoka, Naoharu Mizuno, Mayumi Ishizuka

  ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY 59 2 291 - 300 2010年08月 [査読有り][通常論文]
   

  We measured the level of heavy metal accumulation in lake sediments, herbivorous (Oreochromis niloticus) and carnivorous (Serranochromis thumbergi) fish, and crayfish (Cherax quadricarinatus) from Lake Itezhi-tezhi (ITT) and Lake Kariba. We used atomic absorption spectrophotometry to quantify the levels of seven heavy metals (Cr, Co, Cu, Zn, Cd, Pb, and Ni). The sediment and the herbivorous fish O. niloticus accumulated a very high concentration of Cu in Lake ITT, most likely due to the discharge of Cu waste from a mining area 450 km upstream. The aquatic species we sampled in Lake Kariba had higher concentrations of Cr, Ni, and Pb relative to those in Lake ITT. This is most likely due to anthropogenic activities, such as the use of leaded petrol and antifouling agents in marine paints. Interestingly, we observed a negative correlation between the coefficient of condition (K) and Ni concentration in the crayfish hepatopancreas. Both O. niloticus and the crayfish had much higher biota-sediment accumulation factors (BSAF) for Cu, Zn, and Cd relative to Cr, Co, Pb, and Ni. The rank of BSAF values for O. niloticus (Cu > Cd > Zn) and C. quadricarinatus (Zn > Cd > Cu) differed from the expected ranks based on the general order of affinity of metals (Cd >> Zn > Cu).
• Molecular Cloning of Novel Cytochrome P450 1A Genes from Nine Japanese Amphibian Species

  Shouta M. M. Nakayama, Tomoko Tanaka-Ueno, Kentaro Q. Sakamoto, Shoichi Fujita, Mayumi Ishizuka

  JOURNAL OF VETERINARY MEDICAL SCIENCE 71 10 1407 - 1411 2009年10月 [査読有り][通常論文]
   

  Novel cytochrome P450 1A(CYP1A) cDNA fragments were isolated from the liver of mile Japanese amphibian species using reverse transcription polymerase chain reaction (RT-PCR). Degenerate PCR primers were used to amplify 122-bp fragments of CYP1A cDNAs. Construction of a phylogenetic tree revealed that urodele and anuran amphibians formed two branches. Within the anuran species, three branches were formed: 1) Ranidae and Rhacophoridae, 2) Bufo japonicus formosus and Hyla japonica, and 3) Xenopus laevis. The cDNA nucleotide sequence of these CYP1A fragments showed identities ranging 72-98% (all), 72-78% (Anura vs, Urodela), 75 to 98% (Anura), 81% (Urodela), 74-80% (Xenopus laevis vs. nine Japanese amphibians).

書籍

• トキシコロジー（第3版）

  中山翔太 (担当:分担執筆範囲:7章 環境毒性)
  朝倉書店 2018年03月

講演・口頭発表等

• Effects of PCB exposure on thyroid hormone levels in serum of dogs and cats  [通常講演]

  Kohki Takaguchi, Hiroyuki Nishikawa, Hazuki Mizukawa, Rumi Tanoue, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Shouta M, M. Nakayama, Yoshinori Ikenaka, Tatsuya Kunisue, Mayumi Ishizuka, Shinsuke Tanabe, Hisato Iwata, Kei Nomiyama

  SETAC North America 39th Annual Meeting 2018年11月 ポスター発表
• Avian interspecific differences in rodenticide sensitivity: amino acid sequence and mRNA expression ratio of VKORC1 and VKORC1L1  [通常講演]

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  SETAC North America 39th Annual Meeting. 4th ~ 8th Nov 2018 2018年11月 口頭発表（一般）
• Blood Lead (Pb) Levels and Stable Isotope Ratio among Children, Infants and Mothers in Kabwe, Zambia  [通常講演]

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  SETAC North America 39th Annual Meeting 2018年11月 ポスター発表
• Avian interspecific differences in VKOR activity and inhibition: Amino acid sequence and mRNA expression ratio of VKORC1 and VKORC1L1  [通常講演]

  Shouta M.M. NAKAYAMA, Ayuko MORITA, Yoshinori IKENAKA, Yusuke K. KAWAI, Kazuki TAKEDA, Hazuki MIZUKAWA, Chihiro ISHII, Keisuke SAITO, Yukiko WATANABE, Masaki ITO, Natsuo Ohsawa, Mayumi ISHIZUKA

  2018 International Meeting on 22nd MDO and 33rd JSSX 2018年10月 ポスター発表
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  第66回動物園技術者研究会 2018年09月 ポスター発表
• Inter-species differences of phase II xenobiotics metabolism enzymes in carnivorans  [通常講演]

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  The 6th Sapporo Summer Symposium for One Health (6th SaSSOH) 2018年09月 口頭発表（一般）
• Vegetation status and suppression of Pb accumulation in wild lizards around Pb-Zn mine in Kabwe, Zambia  [通常講演]

  Rio Doya, Shouta M.M. Nakayama, Hokuto Nakata, Haruya Toyomaki, John Yabe, Kaampwe Muzandu, Yared Beyene, Andrew Kataba, Golden Zyambo, Yoshitaka Uchida, Hazuki Mizukawa, Yoshinori Ikenaka, Mayumi Ishizuka

  The 6th Sapporo Summer Symposium for One Health (6th SaSSOH) 2018年09月 ポスター発表
• Does dog’s behavior affect the blood lead levels in domestic dogs around lead mining area, Kabwe, Zambia?  [通常講演]

  Haruya Toyomaki, John Yabe, Shouta M.M. Nakayama, Yared Beyene Yohannes, Kaampwe Muzandu, Hazuki Mizukawa, Yoshinori Ikenaka, Hokuto Nakata, Mayumi Ishizuka

  The 6th Sapporo Summer Symposium for One Health (6th SaSSOH) 2018年09月 口頭発表（一般）
• Effects of zinc co-administration with lead (Pb) on Pb biodistribution in tissues of Sprague Dawley (SD) rats  [通常講演]

  Andrew Kataba, Shouta M.M Nakayama, Yared B. Yohannes, Haruya Toyomaki, Hazuki Mizukawa, Yoshinori Ikenaka, Mayumi Ishizuka

  The 6th Sapporo Summer Symposium for One Health (6th SaSSOH) 2018年09月 ポスター発表
• DNA Methylation Biomarkers in Environmental Lead-Exposed Children from Kabwe, Zambia  [通常講演]

  Yared Beyene Yohannea, Shouta M.M, Nakayama, John Yabe, Toyomaki Haruya, Kaampwe Muzandu, Hokuto Nakata, Hazuki Mizukawa, Yoshinori Ikenaka, Mayumi Ishizuka

  The 6th Sapporo Summer Symposium for One Health (6th SaSSOH) 2018年09月 ポスター発表
• Evaluation of Exposure and Toxicological Implications of Neonicotinoid Insecticides among the residents of Kumasi, Ghana  [通常講演]

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  The 6th Sapporo Summer Symposium for One Health (6th SaSSOH) 2018年09月 ポスター発表
• Charcterization of CYP expression in cat-related PCBs exposure  [通常講演]

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  The 6th Sapporo Summer Symposium for One Health (6th SaSSOH) 2018年09月 ポスター発表
• Assessment of vitamin K epoxide reductase by in vitro kinetic analysis & in silico docking simulation for evaluation of rodenticide sensitivity  [通常講演]

  Kazuki TAKEDA, Yoshinori IKENAKA, Kazuyuki D. TANAKA, Shouta M.M. NAKAYAMA, Tsutomu TANIKAWA, Hazuki Mizukawa, Mayumi ISHIZUKA

  The 6th Sapporo Summer Symposium for One Health (6th SaSSOH) 2018年09月 ポスター発表
• Evaluation of Neonicotinoid Insecticide Exposure and Toxicity among some residents of Kumasi, Ghana  [通常講演]

  Collins NIMAKO, Yoshinori IKENAKA, Osei AKOTO, Nesta BORTEY-SAM, Shouta M.M. NAKAYAMA, Hazuki MIZUKAWA, Mayumi ISHIZUKA

  Society for Environmental Toxicology and Chemistry, Asia-Pacifi 2018 (SETAC-AP2018) 2018年09月 ポスター発表
• グルクロン酸転移酵素UGT1A6と哺乳類の食性の関係  [通常講演]

  佐野花澄, 池中良徳, 近藤誉充, 川合佑典, 中山翔太, 水川葉月, 石塚真由美

  第161回日本獣医学会学術集会 2018年09月 口頭発表（一般）
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  山田尚輝, 中山翔太, 水川葉月, 小笠原浩平, 渡邊有希子, 齊藤慶輔, 伊藤真輝, 大澤夏生, 竹中康進, 小松謙之, 千葉茜, 内田義崇, 池中良徳, 石塚真由美

  第161回日本獣医学会学術集会 2018年09月 口頭発表（一般）
• 誘導体化液体クロマトグラフィー質量分析法（LC/MS法）によるエクイリン・エクイレニンを中心とするステロイドホルモン多成分一斉分析メソッドの開発及びその応用  [通常講演]

  三津橋嵩史, 池中良徳, 一瀬貴大, Aksorn Saengtienchai, 中山翔太, 水川葉月, 河合正人, 南保泰雄, 石塚真由美

  第161回日本獣医学会学術集会 2018年09月 口頭発表（一般）
• 小笠原諸島における殺鼠剤散布が野生動物に及ぼす影響の解明  [通常講演]

  中山翔太, 川合佑典, 武田一貴, 池中良徳

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  中山翔太

  平成30年度育志賞研究発表会 2018年09月 ポスター発表
• 国内に生息する野生鳥類における鉛曝露状況の解明  [通常講演]

  石井 千尋, 池中 良徳, 中山 翔太, 齊藤 慶輔, 渡辺 有希子, 小笠原 浩平, 水川 葉月, 石塚 真由美

  第24回日本野生動物医学会大会 2018年08月 ポスター発表
• 鰭脚類を中心とした食肉目の薬物代謝酵素である硫酸転移酵素の種差解明  [通常講演]

  近藤 誉充, 池中 良徳, 中山 翔太, 水川 葉月, 三谷 曜子, 田辺 信介, 野見山 桂, 石塚 真由美

  第24回日本野生動物医学会大会 2018年08月 ポスター発表
• 殺鼠剤に弱い野生動物種を探る：標的分子ビタミンKエポキシド還元酵素(VKOR)の鳥類における特徴および種差  [通常講演]

  中山翔太, 森田鮎子, 池中良徳, 石井千尋, 水川葉月, 武田一貴, 川合佑典, 齊藤慶輔, 渡邊有希子, 大澤夏生, 伊藤真輝, 石塚真由美

  第24回日本野生動物医学会大会 2018年08月 ポスター発表
• PCR法による鳥類の雌雄判定：孵化前雌雄判定の試みとその課題  [通常講演]

  中山翔太, 池中良徳, 石井千尋, 水川葉月, 川合佑典, 平野なぎ沙, 齊藤慶輔, 渡邊有希子, 大澤夏生, 伊藤真輝, 中村亮平, 石塚真由美

  第24回日本野生動物医学会大会 2018年08月 ポスター発表
• Contamination status and global comparison of organohalogen compounds and their related compounds in the pet cats from Thailand  [通常講演]

  Makoto Shimasaki, Kei Nomiyama, Hazuki Mizukawa, Aksorn Saengtienchai, Araya Ngamchirttakul, Disdanai Pencharee, Yoshinori Ikenaka, Shouta MM Nakayama, Tatsuya Kunisue, Shinsuke Tanabe

  38th International Symposium on Halogenated Persistent Organic Pollutants (POPs) : DIOXIN 2018 2018年08月 ポスター発表
• Pilot study on the toxicological assessment of organohalogen compounds in pet cat (Felis catus) serum using metabolomics approach  [通常講演]

  Kei Nomiyama, Aifumi Eguchi, HazukiMizukawa, Yasuo Yamamoto, Hiroyuki Nishikawa, Mitsuyoshi Takiguchi, Shouta MM Nakayama, Yoshinori Ikenaka, Mayumi Isizuka, Shinsuke Tanabe

  38th International Symposium on Halogenated Persistent Organic Pollutants (POPs) : DIOXIN 2018 2018年08月 口頭発表（一般）
• Effects of Polychlorinated Biphenyls (PCBs) in Cats: Exhaustive Gene Expression Analysis Approach  [通常講演]

  Hazuki Mizukawa, Kraisiri Khidkhan, Yoshinori Ikenaka, Shouta M.M. Nakayama, Kei Nomiyama, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Sainnoxoi Tsend-ayush, Shinsuke Tanabe, Mayumi Ishizuka

  38th International Symposium on Halogenated Persistent Organic Pollutants (POPs) : DIOXIN 2018 2018年08月 口頭発表（一般）
• Tissue distribution and CYP expression related-PCBs exposure in cats  [通常講演]

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  38th International Symposium on Halogenated Persistent Organic Pollutants (POPs) : DIOXIN 2018 2018年08月 口頭発表（一般）
• The estimation of potential PCBs toxicity in cats by evaluating CYP450 expressions  [通常講演]

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  38th International Symposium on Halogenated Persistent Organic Pollutants (POPs) : Pre- Dioxin 2018 Students’ Symposium 2018年08月 ポスター発表
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  2nd International KAMPAI Symposium & JST Mid-term Evaluation Meeting 2018年08月 ポスター発表
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  2nd International KAMPAI Symposium & JST Mid-term Evaluation Meeting 2018年08月 ポスター発表
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  2nd International KAMPAI Symposium & JST Mid-term Evaluation Meeting 2018年08月 ポスター発表
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  第45回 日本毒性学会学術年会 2018年07月 ポスター発表
• ザンビア共和国カブウェ鉱床地域における鉛汚染問題：10年間の研究結果と今後の課題  [通常講演]

  中山翔太, John Yabe, 池中良徳, Kaampwe Muzandu, Kennedy Choongo, 中田北斗, 豊巻治也, Yared Beyene, Andrew Kataba, Golden Zyambo, 栗谷豪, 中川光弘, 水川葉月, 石塚真由美

  第45回 日本毒性学会学術年会 2018年07月 口頭発表（一般）
• ポリ塩化ビフェニル曝露によるイヌ・ネコの甲状腺ホルモン恒常性への影響  [通常講演]

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  第45回日本毒性学会学術年会 2018年07月 ポスター発表
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  9th International Conference on Children and the Environment (INCHES) 2018年06月 口頭発表（招待・特別）
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  2018（平成30）年度 海外学術調査フォーラム 2018年06月 ポスター発表
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  2018 ACVIM Forum (American College of Veterinary Internal Medicine) 2018年06月 ポスター発表
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  7th Zambia Water Forum and Exhibition 2018年06月 口頭発表（招待・特別）
• Distribution of Pb in mice organs using bioimaging by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS)  [招待講演]

  Shouta M.M. Nakayama, Masao Togao, Yoshinori Ikenaka, Hazuki Mizukawa, Yoshiki Makino, Ayano Kubota, Takehisa Matsukawa, Kazuhito Yokoyama, Takafumi Hirata, Mayumi Ishizuka

  7th Zambia Water Forum and Exhibition 2018年06月 口頭発表（招待・特別）
• Current trends of childhood Blood lead levels and Exposure patterns in Kabwe  [招待講演]

  John Yabe, Shouta M.M. Nakayama, Haruya Toyomaki, Yared Beyene Yohannes, Hokuto Nakata, Kaampwe Muzandu, Andrew Kataba, Golden Zyambo, Nosiku S. Munyinda, Kennedy Choongo, Tiza Mfune, Paul Mukuka, Jack Caravanos, Mayumi Ishizuka

  7th Zambia Water Forum and Exhibition 2018年06月 口頭発表（招待・特別）
• The trend of elevated blood lead levels in mining area, Kabwe, Zambia  [通常講演]

  Hokuto Nakata, Shouta M.M, Nakayama, John Yabe, Kaampwe Muzandu, Yared B. Yohannes, Haruya Toyomaki, Andrew Kataba, Golden Zyambo, Hazuki Mizukawa, Yoshinori Ikenaka, Russell Dowling, Jack Caravanos, Mayumi Ishizuka

  日本アフリカ学会第５５回学術大会 2018年05月 口頭発表（一般）
• Analysis of the amino acid metabolome in p,p’-DDT exposed chickens  [通常講演]

  Lesa A Thompson, Isabel M Vincent, Yoshinori Ikenaka, Stefan K Weidt, Wageh S Darwish, Shouta MM Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  第27回環境化学討論会 2018年05月 口頭発表（一般）
• マラリアベクターコントロールにおけるDDTの使用実態とリスク評価  [通常講演]

  池中良徳, リサ トンプソン, ダルウィッシュ ワギ, ヨハネス ヤレド, ファンファーレン ヨハン, スミッツ ニコ, ヴェペナー ヴィクター, 中山翔太, 水川葉月, 石塚真由美

  第27回環境化学討論会 2018年05月 口頭発表（一般）
• ネオニコチノイド系殺虫剤のヒト健康影響評価問題点の整理と今後の研究課題  [通常講演]

  池中良徳, 一瀬貴大, ニマコ コリンズ, 市川剛, 水川葉月, 中山翔太, 有薗幸司, 石塚真由美

  第27回環境化学討論会 2018年05月 口頭発表（一般）
• 誘導体化LC/MS/MS法による血漿中のステロイドホルモンおよびその抱合体代謝物35種類の一斉分析法の開発とその応用  [通常講演]

  一瀬貴大, 池中良徳, Aksorn Saengtienchai, 中山翔太, 水川葉月, 石塚真由美

  第27回環境化学討論会 2018年05月 ポスター発表
• 野生哺乳類における硫酸転移酵素の動物種差解明  [通常講演]

  近藤誉充, 池中良徳, 中山翔太, 水川葉月, 三谷曜子, 田辺信介, 野見山桂, 石塚真由美

  第27回環境化学討論会 2018年05月 口頭発表（一般）
• タイ王国におけるペットネコ血清およびペットフード中有機ハロゲン化合物と類縁化合物の汚染実態  [通常講演]

  島崎真琴, 野見山桂, 水川葉月, Aksorn Saengtienchai, Araya Ngamchirttakul, Disdanai Pencharee, 石塚真由美, 池中良徳, 中山翔太, 国末達也, 田辺信介

  第27回環境化学討論会 2018年05月 口頭発表（一般）
• 血清中メタボローム解析によるペットネコ（Felis catus）の有機ハロゲン化合物毒性影響評価  [通常講演]

  野見山桂, 江口哲史, 水川葉月, 山本恭央, 西川博之, 滝口満喜, 中山翔太, 池中良徳, 石塚真由美, 田辺信介

  第27回環境化学討論会 2018年05月 口頭発表（一般）
• ネコのin vivo BDE209長期曝露試験による体内動態の解明および甲状腺ホルモンへの影響評価  [通常講演]

  田中啓介, 野見山桂, 水川葉月, 高口倖暉, 田上瑠美, 横山望, 市居修, 滝口満喜, 笹岡一慶, 中山翔太, 池中良徳, 石塚真由美, 国末達也, 田辺信介

  第27回環境化学討論会 2018年05月 口頭発表（一般）
• 有機ハロゲン化合物曝露によるネコの生化学マーカーの変化および甲状腺機能に及ぼす影響評価  [通常講演]

  水川葉月, Kraisiri Khidkhan, 高口倖暉, 横山望, 市居修, 滝口満喜, 笹岡一慶, 池中良徳, 中山翔太, 野見山桂, 田辺信介, 石塚真由美

  第27回環境化学討論会 2018年05月 口頭発表（一般）
• Characteristics of CYP450 expression in cat exposed PCBs: Estimating the potential toxicity  [通常講演]

  Kraisiri Khidkhan, Hazuki Mizukawa, Kei Nomiyama, Yoshinori Ikenaka, Shota M, M. Nakayama, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Hiroyuki Nishikawa, Keisuke Tanaka, Kohki Takiguchi, Shinsuke Tanabe, Mayumi Ishizuka

  第27回環境化学討論会 2018年05月 口頭発表（一般）
• HPLC-APCI-MSを用いたビタミンKの網羅的検出とin vitroビタミンKエポキシド還元酵素活性の評価  [通常講演]

  武田一貴, 池中良徳, 田中和之, 中山翔太, 谷川力, 水川葉月, 石塚真由美

  第27回環境化学討論会 2018年05月 口頭発表（一般）
• 鉛鉱床地域における野生トカゲ亜目の生体内金属類濃度に影響を与える環境要因の解析  [通常講演]

  銅谷理緒, 中山翔太, 中田北斗, 豊巻治也, Yabe John, Muzandu Kaampwe, Beyene Yared, Kataba Andrew, yambo Golden, 水川 葉月, 池中 良徳, 石塚 真由美

  第27回環境化学討論会 2018年05月 口頭発表（一般）
• GPS装置を用いた鉛鉱床地域のイヌの行動のモニタリングと鉛曝露の関係性  [通常講演]

  豊巻治也, Yabe John, 中山翔太, Beyene Yared, 水川葉月, 池中良徳, 中田北斗, 石塚真由美

  第27回環境化学討論会 2018年05月 口頭発表（一般）
• Utility of Pb isotopes for source identification and species differences of Pb isotope biological fractionation  [通常講演]

  Hokuto Nakata, Shouta M.M, Nakayama, John Yabe, Allan Liazambi, Hazuki Mizukawa, Wageh S. Darwish, Yoshinori Ikenaka, Mayumi Ishizuka

  第27回環境化学討論会 2018年05月 口頭発表（一般）
• Evaluation of Neonicotinoid Insecticide exposure in humans living in the Kumasi city, Ghana  [通常講演]

  Collins Nimako, Yoshinori Ikenaka, Osei Akoto, Nesta Bortey-Sam, Shouta M.M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  第27回環境化学討論会 2018年05月 口頭発表（一般）
• Lead (Pb) accumulation in tissues of Sprague Dawley (SD) rats following sub chronic Lead-Zinc exposure  [通常講演]

  Andrew Kataba, Shouta Nakayama, Yared B. Yohannes, Haruya Toyomaki, Hazuki Mizukawa, Yoshinori Ikenaka, Mayumi Ishizuka

  第27回環境化学討論会 2018年05月 口頭発表（一般）
• Blood Lead Levels Among the General Population in Kabwe, Zambia  [通常講演]

  Yared B. Yohannes, Shouta Nakayama, John Yabe, Hokuto Nakata, Haruya Toyomaki, Kaampwe Muzandu, Andrew Kataba, Yoshinori Ikenaka, Hazuki Mizukawa, Russell Dowling, Jack Caravanos, Mayumi Ishizuka

  第27回環境化学討論会 2018年05月 口頭発表（一般）
• 非侵襲的に採取可能な乳幼児の糞便における鉛安定同位体比を用いた鉛暴露経路の推定  [通常講演]

  中山翔太, 豊巻治也, John Yabe, Kaampwe Muzandu, 中田北斗, 栗谷豪, 中川光弘, 水川葉月, 池中良徳, 石塚真由美

  第27回環境化学討論会 2018年05月 口頭発表（一般）
• クロミンククジラ未成熟雌のヒゲ板安定同位体比を用いた摂餌履歴推定  [通常講演]

  打田茉由果, 鈴木一平, 石塚真由美, 池中良徳, 中山翔太, 水川葉月, 田村 力, 坂東武治, 小西健志, 三谷曜子

  平成30年度日本水産学会春季大会 2018年03月 口頭発表（一般）
• Novel Mechanism of Rodenticide (warfarin) Resistance of Wild Rats in Tokyo ~ Enhanced Pentose Phosphate Pathway Causes Rapid Metabolism of Warfarin ~  [通常講演]

  Kazuki Takeda, Yoshinori Ikenaka, Tsutomu Tanikawa, Kazuyuki D. Tanaka, Shouta M.M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  Society of Toxicology’s 57th Annual Meeting and ToxExpo 2018年03月 ポスター発表
• Lead levels in eggs in Kabwe, Zambia: implication of human exposure  [通常講演]

  Haruya Toyomaki, John Yabe, Shouta M.M. Nakayama, Yared B. Yohannes, Kaampwe Muzandu, Hazuki Mizukawa, Yoshinori Ikenaka, Hokuto Nakata, Takeshi Kuritani, Mitsuhiro Nakagawa, Mayumi Ishizuka

  Society of Toxicology’s 57th Annual Meeting and ToxExpo 2018年03月 ポスター発表
• Migratory seabirds are responsible for mercury biotransport from marine to terrestrial ecosystems  [通常講演]

  Shoji, A, K. H. Elliott, S. Aris-Brosou, H. Mizukawa, S. Nakayama, Y. Ikenaka, M. Ishizuka, T. Kuwae, K. Watanabe, Y. Watanuki

  The 45th Pacific Seabird Group Annual Meeting 2018年02月 口頭発表（一般）
• 犬の特発性てんかんにおける血中及び脳脊髄液中微量元素濃度の検討  [通常講演]

  笹岡一慶, 大田寛, 水川葉月, 中山翔太, 佐々木東, 森下啓太郎, 池中良徳, 石塚真由美, 滝口満喜

  第14回 日本獣医内科学アカデミー学術大会（JCVIM 2018） 2018年02月 口頭発表（一般）
• ザンビア・カブエ鉱床における鉛汚染問題とその解決に向けた取り組み-KAbwe Mine Pollution Amelioration Initiative (KAMPAI Project)  [通常講演]

  中山翔太, 水川葉月, 池中良徳, 石塚真由美

  第3回 北大部局間横断シンポジウム 2018年01月 口頭発表（一般）
• スーパーラットは高NADPH産生能を持つ〜東京の殺鼠剤抵抗性ラットにおける抵抗性獲得機序の解明〜  [通常講演]

  武田一貴, 池中良徳, 田中和之, 谷川力, 中山翔太, 水川葉月, 石塚真由美

  第3回 北大部局間横断シンポジウム 2018年01月 ポスター発表
• 幼児および新生児におけるネオニコチノイド系殺虫剤の曝露実態  [通常講演]

  池中良徳, 宮原裕一, 一瀬貴大, 中山翔太, 水川葉月, 市川剛, 遠山千春, 石塚真由美

  環境ホルモン学会第20回研究発表会 2017年12月 口頭発表（一般）
• Evaluation of indoor residual spraying DDT for mosquito control: Tissue distribution and gene expression profiling in rat tissues  [通常講演]

  Emmanuel Temiotan, Ogbomida, Alex Ajeh Enuneku, Yoshinori Ikenaka, Yared Beyene Yohannes, Wageh Sobhy Darwish, Shouta M.M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  環境ホルモン学会第20回研究発表会 2017年12月 ポスター発表
• ポリ塩化ビフェニル（PCBs）がネコの甲状腺機能に及ぼす影響  [通常講演]

  水川葉月, 高居名菜, 野見山桂, 高口倖暉, 横山望, 市居修, 滝口満喜, 池中良徳, 中山翔太, 石塚真由美

  環境ホルモン学会第20回研究発表会 2017年12月 ポスター発表
• 東京のワルファリン抵抗性ラットの抵抗性獲得機序の解明：ペントースリン酸経路の亢進を通したワルファリン代謝の活性化  [通常講演]

  Kazuki Takeda, Yoshinori Ikenaka, Tsutomu Tanikawa, Kazuyuki D. Tanaka, Shouta M.M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  2017年度生命科学系学会合同年次大会（ConBio2017） 2017年12月 口頭発表（一般）
• Russell Dowling, Jack Caravanos, Hokuto Nakata, Mayumi Ishizuka, Elevated Blood Lead Levels among Children, Infants and Mothers in Kabwe, Zambia  [通常講演]

  Yared Beyene Yohannes, John Yabe, Shouta M.M. Nakayama, Haruya Totomaki, Kaampwe Muzandu, Yoshinori Ikenaka, Hazuki Mizukawa

  SETAC North America 38th Annual Meeting 2017年11月 口頭発表（一般）
• Biochemical Alterations due to PCBs and PBDEs Exposures in Cats  [通常講演]

  Kraisiri Khidkhan, Hazuki Mizukawa, Kei Nomiyama, Yoshinori Ikenaka, Shouta M, M. Nakayama, Nozomu Yokoyama, Kazuyoshi Sasaoka, Osamu Ichii, Mitsuyoshi Takiguchi, Hiroyuki Nishikawa, Keisuke Tanaka, Kohki Takiguchi, Shinsuke Tanabe, Mayumi Ishizuka

  SETAC North America 38th Annual Meeting 2017年11月 ポスター発表
• Evaluation of utility for stable lead isotope ratios to identify lead sources and verifying biological fractionation of lead isotopes in goats and chickens  [通常講演]

  Hokuto Nakata, Shouta M.M, Nakayama, John Yabe, Allan Liazambi, Hazuki Mizukawa, Wageh Sobhy Darwish, Yoshinori Ikenaka, Mayumi Ishizuka

  SETAC North America 38th Annual Meeting 2017年11月 ポスター発表
• Local distribution of Pb in mice using bioimaging by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS)  [通常講演]

  Shouta MM Nakayama, Masao Togao, Yoshinori Ikenaka, Hazuki Mizukawa, Yoshiki Makino, Ayano Kubota, Takehisa Matsukawa, Kazuhito Yokoyama, Takafumi Hirata, Mayumi Ishizuka

  1st International KAMPAI Symposium on Sustainable Management of Resources and Environment in the 21st Century 2017年11月 ポスター発表
• Practical system integration for local community participation in lead contamination assessment in Kabwe, Zambia  [通常講演]

  Shinsaku Nakamura, Kazuyo Hirose, Tomomi Takeda, Yoshitaka Uchida, Hokuto Nakata, Shouta MM Nakayama, Mayumi Ishizuka, John Yabe, Mayumi Ito, Toshifumi Igarashi

  1st International KAMPAI Symposium on Sustainable Management of Resources and Environment in the 21st Century 2017年11月 ポスター発表
• Reliability of stable lead isotope analysis for lead source identification and verifying biological fractionation of lead isotopes in goats and chicken  [通常講演]

  Hokuto Nakata, Shouta M.M, Nakayama, John Yabe, Allan Liazambi, Hazuki Mizukawa, Wageh S Darwish, Yoshinori Ikenaka, Mayumi Ishizuka

  1st International KAMPAI Symposium on Sustainable Management of Resources and Environment in the 21st Century 2017年11月 ポスター発表
• Extent of lead exposure in mothers and infants living around a “closed” lead mining area, Kabwe, Zambia  [通常講演]

  Haruya Toyomaki, John Yabe, Shouta M.M. Nakayama, Yared B. Yohannes, Kaampwe Muzandu, Hazuki Mizukawa, Yoshinori Ikenaka, Hokuto Nakata, Russell Dowling, Jack Caravanos, Mayumi Ishizuka

  1st International KAMPAI Symposium on Sustainable Management of Resources and Environment in the 21st Century 2017年11月 口頭発表（一般）
• Current trends of blood lead levels in Kabwe, Zambia  [通常講演]

  Yared Beyene Yohannes, John Yabe, Shota M.M. Nakayama, Haruya Toyomaki, Hokuto Nakata, Kaampwe Muzandu, Andrew Kataba, Golden Zyambo, Hazuki Mizukawa, Yoshinori Ikenaka, Russell Dowling, Jack Caravanos, Mayumi Ishizuka

  1st International KAMPAI Symposium on Sustainable Management of Resources and Environment in the 21st Century 2017年11月 口頭発表（一般）
• Discovery of renal biomarkers in birds by transcriptome analysis and glycomics analysis following kidney injury in chicken model  [通常講演]

  Chihiro Ishii, Yoshinori Ikenaka, Yusuke K. Kawai, Osamu Ichii, Shouta. M, M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  The 10th International Meeting of the Asian Society of Conservation Medicine (ASCM) 2017年10月 ポスター発表
• Indoor exposure for polychlorinated biphenyls (PCBs) in domestic cats ~Pilot study of Mongolian pet cat~  [通常講演]

  Hazuki Mizukawa, Yoshinori Ikenaka, Tsend-Ayush Sainnoxoi, Kohki Takaguchi, Kei Nomiyama, Shouta M.M. Nakayama, Mayumi Ishizuka

  The 2nd Symposium on the Improvement of Diagnosis and Prevention of some Diseases Caused by Environmental Change 2017年10月 口頭発表（一般）
• “First, do no harm” ? balancing the benefits of malaria control against the toxic effects of DDT use  [通常講演]

  Lesa THOMPSON, Yoshinori IKENAKA, Yared YOHANNES, Atnafu ASSEFA, Johan VAN VUREN, Victor WEPENER, Nico SMIT, Wynand VLOK, Wageh Sobhy DARWISH, Shouta NAKAYAMA, Hazuki MIZUKAWA, Mayumi ISHIZUKA

  The 5th Sapporo Summer Seminar for One Health (SaSSOH) 2017年09月 口頭発表（一般）
• Drug metabolism enzymes in Carnivora species  [通常講演]

  Takamitsu Kondo, Yoshinori Ikenaka, Shouta M.M. Nakayama, Yusuke K. Kawai, Hazuki Mizukawa, Yoko Mitani, Kei Nomyama, Shinsuke Tanabe, Mayumi Ishizuka

  The 5th Sapporo Summer Seminar for One Health (SaSSOH) 2017年09月 ポスター発表
• Discovery of renal biomarker in birds by transcriptome analysis of kidney tissues and glycomics analysis of plasma following renal damage in chicken model  [通常講演]

  Chihiro Ishii, Yoshinori Ikenaka, Yusuke K. Kawai, Osamu Ichii, Shouta. M.M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  The 5th Sapporo Summer Seminar for One Health (SaSSOH) 2017年09月 ポスター発表
• Blood Lead Levels in chickens and dogs around lead mining area, Kabwe, Zambia  [通常講演]

  Haruya Toyomaki, Shouta M.M. Nakayama, Yared B. Yohannes, John Yabe, Kaampwe Muzandu, Hazuki Mizukawa, Yoshinori Ikenaka, Mayumi Ishizuka

  The 5th Sapporo Summer Seminar for One Health (SaSSOH) 2017年09月 ポスター発表
• Effects of Organohalogen Compounds on Serum Biochemical Profiles in Cats  [通常講演]

  Kraisiri Khidkhan, Hazuki Mizukawa, Kei Nomiyama, Yoshinori Ikenaka, Shota M.M. Nakayama, Nozomu Yokoyama, Kazuyoshi Sasaoka, Osamu Ichii, Mitsuyoshi Takiguchi, Hiroyuki Nishikawa, Keisuke Tanaka, Kohki Takiguchi, Shinsuke Tanabe, Mayumi Ishizuka

  The 5th Sapporo Summer Seminar for One Health (SaSSOH) 2017年09月 ポスター発表
• Nobel investigation of mechanism of rodenticide resistance ~ enhanced pentose phosphate pathway causes rapid metabolism of warfarin ~  [通常講演]

  Kazuki Takeda, Yoshinori Ikenaka, Tsutomu Tanikawa, Kazuyuki D. Tanaka, Shouta M.M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  The 5th Sapporo Summer Seminar for One Health (SaSSOH) 2017年09月 口頭発表（一般）
• 海鳥を介した汚染物質輸送  [通常講演]

  庄子晶子, K. Elliott, S. Aris-Brosou, 水 川葉月, 中山翔太, 池中良徳, 石塚真由美, 桑江朝比呂, 渡辺謙太, 綿貫豊

  日本鳥学会2017年度大会 2017年09月 口頭発表（一般）
• 鳥類におけるグルクロン酸抱合能の種差の解明と化学物質感受性の推定  [通常講演]

  新屋惣, 池中良徳, 中山翔太, 水川葉月, 伊藤真輝, 高江洲昇, 齊藤 慶輔, 渡邊 有希子, 石塚 真由美

  日本鳥学会2017年度大会 2017年09月 ポスター発表
• 鳥類医学の発展に向けた新規腎障害マーカーの探索  [通常講演]

  石井千尋, 池中良徳, 川合佑典, 市居修, 中山翔太, 西村紳一郎, 大橋哲, 田中誠一, 齊藤慶輔, 渡邊有希子, 水川葉月, 石塚真由美

  日本鳥学会2017年度大会 2017年09月 ポスター発表
• 東京由来殺鼠剤抵抗性ラットを用いた新規抵抗性獲得機序の解明 ~ペントースリン酸経路の亢進による殺鼠剤代謝能の活性化~  [通常講演]

  武田一貴, 池中良徳, 田中和之, 谷川力, 中山翔太, 水川葉月, 石塚真由美

  第160回日本獣医学会学術年会 2017年09月 口頭発表（一般）
• Wild rat’s bio-distribution analysis for pesticide DDT from South Africa  [通常講演]

  Tetsuro Ogawa, Yoshinori Ikenaka, Yared B Yohannes, Lesa Thompson, Johan van Vuren, Victor Wepener, Nico J Smit, Wynand Vlok, Shouta M.M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  9th International Toxicology Symposium in Nigeria 2017年09月 ポスター発表
• UDP-glucuronosyltransferase (UGT) 2B genetic feature and activities in Carnivores  [通常講演]

  Takamitsu Kondo, Yoshinori Ikenaka, Shouta M.M. Nakayama, Yusuke K. Kawai, Hazuki Mizukawa, Yoko Mitani, Kei Nomyama, Shinsuke Tanabe, Mayumi Ishizuka

  9th International Toxicology Symposium in Nigeria 2017年09月 口頭発表（一般）
• Short-term or long-term in vivo exposure to organohalogen compounds in cats: Elucidate the metabolic capacities and effects on thyroid function  [通常講演]

  Hazuki Mizukawa, Yoshinori Ikenaka, Shouta M.M. Nakayama, Kei Nomiyama, Misaki Maehara, Aksorn Saengtienchai, Tsend-ayush Sainnoxoi, Kraisiri Khidkhan, Nozomu Yokoyama, Kazuyoshi Sasaoka, Osamu Ichii, Mitsuyoshi Takiguchi, Khoki Takaguchi, Hiroki Nishikawa, Nana Takai, Shinsuke Tanabe, Mayumi Ishizuka

  9th International Toxicology Symposium in Nigeria 2017年09月 口頭発表（一般）
• The relationship of Blood Lead Levels between mothers and infants in Kabwe, Zambia  [通常講演]

  Haruya Toyomaki, John Yabe, Shouta M.M. Nakayama, Yared B. Yohannes, Kaampwe Muzandu, Hazuki Mizukawa, Yoshinori Ikenaka, Hokuto Nakata, Russell Dowling, Jack Caravanos, Mayumi Ishizuka

  9th International Toxicology Symposium in Nigeria 2017年09月 口頭発表（一般）
• Trends of childhood blood lead levels and remedial options in Kabwe, Zambia  [通常講演]

  ohn Yabe, Haruya Toyomaki, Shouta M.M. Nakayama, Yared B. Yohannes, Kaampwe Muzandu, Andrew Kataba, Kennedy Choongo, Russell Dowling, Jack Caravanos, Yoshinori Ikenaka, Mayumi Ishizuka

  9th International Toxicology Symposium in Nigeria 2017年09月 口頭発表（一般）
• Heavy metal residues in some ready-to-eat meat products marketed in Egypt  [通常講演]

  Wageh Sobhy Darwish, Yoshinori Ikenaka, Shouta M.M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  9th International Toxicology Symposium in Nigeria 2017年09月 口頭発表（一般）
• 全国規模での鳥類への鉛曝露：曝露指標として骨の利用の可能性  [通常講演]

  石井千尋, 中山翔太, 池中良徳, Kataba Andrew, 齊藤慶輔, 渡辺有希子, 槇納好岐, 松川岳久, 久保田章乃, 横山和仁, 水川葉月, 平田岳史, 石塚真由美

  第23回日本野生動物医学会大会 2017年09月 口頭発表（一般）
• エストロジェン類高感度分析法の開発と野生動物におけるスクリーニング  [通常講演]

  新屋惣, 池中良徳, 中山翔太, 石井千尋, 水川葉月, 伊藤真輝, 高江洲昇, 大澤夏生, 綿貫豊, 石塚 真由美

  第23回日本野生動物医学会大会 2017年09月 ポスター発表
• in vivo exposure to PCBs in cats: Analysis of metabolic capacities and effects on the thyroid hormone homeostasis  [通常講演]

  Hazuki Mizukawa, Kei Nomiyama, Hiroyuki Nishikawa, Misaki Maehara, Nana Takai, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Yoshinori Ikenaka, Shouta M.M. Nakayama, Kohki Takaguchi, Shinsuke Tanabe, Mayumi Ishizuka

  37th International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN 2017) 2017年08月 口頭発表（一般）
• Utility evaluation for stable Pb isotopes analysis using potential sentinel animals to identify Pb pollution sources  [通常講演]

  Hokuto Nakata, Shouta M.M, Nakayama, John Yabe, Allan Liazambi, Hazuki Mizukawa, Wageh Sobhy Darwish, Yoshinori Ikenaka, Mayumi Ishizuka

  International Conference on Geology, Mining, Mineral and Groundwater Resources of the Sub-Saharan Africa 2017年07月 口頭発表（一般）
• 幼児のネオニコチノイド系農薬の曝露評価に関する研究  [通常講演]

  池中良徳, 宮原裕一, 一瀬貴大, 八木橋美緒, 中山翔太, 水川葉月, 平久美子, 有薗幸司, 高橋圭介, 加藤恵介, 遠山千春, 石塚真由美

  第44回日本毒性学会学術年会 2017年07月 口頭発表（一般）
• 肝灌流試験、in vitro酵素活性試験による東京由来ワルファリン抵抗性クマネズミのワルファリン代謝能の解明  [通常講演]

  武田一貴, 池中良徳, 田中和之, 谷川力, 中山翔太, 水川葉月, 石塚真由美

  第44回日本毒性学会学術年会 2017年07月 口頭発表（一般）
• Studies on polycyclic aromatic hydrocarbons formation in heat-treated meat  [通常講演]

  Wageh Sobhy Darwish, Yoshinori Ikenaka, Shouta M.M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  第44回日本毒性学会学術年会 2017年07月 口頭発表（一般）
• ポリ塩化ビフェニル（PCBs）のin vivo暴露によるネコの異物代謝解明と甲状腺ホルモンへの影響評価  [通常講演]

  水川葉月, 前原美咲, 横山望, 市居修, 滝口満喜, 野見山桂, 西川博之, 池中良徳, 中山翔太, 高口倖暉, 田辺信介, 石塚真由美

  第44回日本毒性学会学術年会 2017年07月 ポスター発表
• Inveatigation of biochemical changes in cat exposed organohalogen compounds  [通常講演]

  Kraisiri Khidkhan, Hazuki Mizukawa, Kei Nomiyama, Yoshinori Ikenaka, Shota M, M. Nakayama, Nozomu Yokoyama, Kazuyoshi Sasaoka, Osamu Ichii, Mitsuyoshi Takiguchi, Hiroyuki Nishikawa, Keisuke Tanaka, Kohki Takiguchi, Shinsuke Tanabe, Mayumi Ishizuka

  the 19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO 19) 2017年06月 ポスター発表
• UDP-glucuronosyltransferase (UGT) among Pinnipedia and other carnivores  [通常講演]

  Takamitsu Kondo, Yoshinori Ikenaka, Shouta M.M. Nakayama, Yusuke K. Kawai, Hazuki Mizukawa, Yoko Mitani, Kei Nomiyama, Shinsuke Tanabe, Mayumi Ishizuka

  the 19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO 19) 2017年06月 口頭発表（一般）
• 高次栄養段階生物への化学物質の感受性の種差  [通常講演]

  石塚真由美, 中山翔太, 水川葉月, 池中良徳

  2017年度第31回環境ホルモン学会講演会 2017年06月 口頭発表（一般）
• Introduction of “The project for Visualization of impact of chronic / latent chemical hazard and Geo-Ecological Remediation” in Kabwe, Zambia  [通常講演]

  Hokuto Nakata, Yoshitaka Uchida, Kaampwe Muzandu, Kawawa Banda, Shouta M.M, Nakayama, John Yabe, Toshifumi Igarashi, Mayumi Ito, Imasiku Nyambe, Mayumi Ishizuka

  The sixth Zambia Water Forum and Exhibition 2017年06月 口頭発表（一般）
• 幼児における尿中ネオニコチノイド濃度とその曝露実態の解明  [通常講演]

  池中良徳, 宮原裕一, 一瀬貴大, 八木橋美緒, 中山翔太, 水川葉月, 遠山千春, 石塚真由美

  第26回環境化学討論会 2017年06月 口頭発表（一般）
• In situ肝灌流試験によるワルファリン抵抗性クマネズミでのワルファリン代謝能の解明  [通常講演]

  武田一貴, 池中良徳, 田中和之, 谷川力, 中山翔太, 水川葉月, 石塚真由美

  第26回環境化学討論会 2017年06月 ポスター発表
• A Pilot Study on Exposure of Lead (Pb) and Its Blood Level Burden in Children from Kabwe, Zambia: Implication to the General Population  [通常講演]

  Yared B. Yohannes, Shouta M.M. Nakayama, Haruya Toyomaki, John Yabe, Kaampwe Muzandu, Andrew Kataba, Yoshinori Ikenaka, Hazuki Mizukawa, Russell Dowling, Jack Caravanos, Mayumi Ishizuka

  第26回環境化学討論会 2017年06月 口頭発表（一般）
• ヒト生体試料を用いたネオニコチノイドおよびネオニコチノイド代謝物の分析方法  [通常講演]

  一瀬貴大, 池中良徳, 藤岡一俊, 平久美子, 中山翔太, 水川葉月, 八木橋美緒, 有薗幸司, 加藤恵介, 高橋圭介, 石塚真由美

  第26回環境化学討論会 2017年06月 ポスター発表
• Blood Lead Levels in chickens and dogs around lead mining area, Kabwe, Zambia  [通常講演]

  Haruya Toyomaki, Shouta M.M. Nakayama, Yared B. Yohannes, John Yabe, Kaampwe Muzandu, Hazuki Mizukawa, Yoshinori Ikenaka, Mayumi Ishizuka

  第26回環境化学討論会 2017年06月 口頭発表（一般）
• イエネコのin vivo長期曝露試験：デカブロモジフェニルエーテル(BDE209)の生体内変化  [通常講演]

  田中啓介, 野見山桂, 水川葉月, 口倖暉, 田上瑠美, Aksorn Saengtienchai、Tsend-ayush Sainnoxoi, 横山望, 市居修, 滝口満喜, 中山翔太, 池中良徳, 石塚真由美, 国末達也, 田辺信介

  第26回環境化学討論会 2017年06月 口頭発表（一般）
• PCBs曝露がイヌ・ネコの甲状腺ホルモン恒常性へ及ぼす影響  [通常講演]

  ????A???R?j?A?, ?A?, A?c?, ?A?F?, ?A??R, ?A??, A, A, 稍??A?r?, A?, ?R??A??c?, l?A?, B, ?A?c??M?

  第26回環境化学討論会 2017年06月 口頭発表（一般）
• 血清中メタボローム解析によるイエネコのPCBs毒性影響評価  [通常講演]

  野見山桂, 西川 博之, 水川葉月, 口倖暉, Tsend-ayush Sainnoxoi, 横山 望, 市居修, 滝口満喜, 石塚真由美, 池中良徳, 中山翔太, 江口哲史, 国末達也, 田辺信介

  第26回環境化学討論会 2017年06月 口頭発表（一般）
• ポリ塩化ビフェニル（PCBs）暴露によるネコ甲状腺機能への影響評価〜甲状腺ホルモンの脱ヨード化と代謝能の解析〜  [通常講演]

  水川葉月, 高居名菜, 横山望, 市居修, 滝口満喜, 野見山桂, 高口倖暉, 西川博之, 池中良徳, 中山翔太, Tsend-ayush Sainnoxoi, 田辺信介, 石塚真由美

  第26回環境化学討論会 2017年06月 口頭発表（一般）
• イエネコのin vivo長期曝露試験：デカブロモジフェニルエーテル（BDE209）は甲状腺機能亢進症を引き起こすのか？  [通常講演]

  水川葉月, 野見山桂, 池中良徳, 中山翔太, Aksorn Saengtienchai、Tsend-ayush Sainnoxoi, 横山望, 笹岡一慶, 市居修, Kraisiri Khidkhan, 高居名菜, 滝口満喜, 田辺信介, 石塚真由美

  第26回環境化学討論会 2017年06月 口頭発表（一般）
• Comparison of Food Products Contaminated by DDTs in South Africa and Mozambique  [通常講演]

  Lesa A. Thompson, Yoshinori Ikenaka, Victor Wepener, Mayumi Ishizuka

  19th International Conference on One Health 2017年05月 口頭発表（一般）
• 代謝酵素の動物種差  [招待講演]

  石塚真由美, 中山翔太, 水川葉月, 池中良徳

  日本薬学会第137年会シンポジウム 2017年03月 口頭発表（招待・特別）
• In situ肝灌流モデルによる殺鼠剤抵抗性野生クマネズミにおけるワルファリン代謝能の解明  [通常講演]

  武田一貴, 池中良徳, 田中和之, 中山翔太, 谷川力, 水川葉月, 石塚真由美

  第39回日本分子生物学会年会 2016年11月 ポスター発表
• 化学物質の汚染環境に生きる野生動物の適応戦略  [招待講演]

  石塚真由美, 中山翔太, 水川葉月, 池中良徳

  一般社団法人日本環境化学会25周年記念講演会：「環境化学の今、そして未来へ−環境化学からの提言−」 2016年11月 口頭発表（招待・特別）
• Monitoring of blood lead levels (BLLs) in dogs and chickens from lead pollution area, Kabwe, Zambia.  [通常講演]

  Haruya Toyomaki, Shouta M.M. Nakayama, Yared B. Yohannes, John Yabe, Kaampwe Muzandu, Hazuki Mizukawa, Yoshinori Ikenaka, Mayumi Ishizuka

  International Doctoral Symposium on Sustainable Management of Resources and Environment in the 21st Century 2016年11月 ポスター発表
• Contamination status of organohalogen compounds and their hydroxylated metabolites in pet cats and dogs: effects on thyroid hormones homeostasis.  [通常講演]

  Kei Nomiyama, Yasuo Yamamoto, Hazuki Mizukawa, Mitsuyoshi Takiguchi, Akifumi Eguchi, Shouta M.M. Nakayama, Yoshinori Ikenaka, Mayumi Ishizuka, Tatsuya. Kunisue, Shinsuke Tanabe

  The 7th SETAC World Congress/37th SETAC North America Annual Meeting 2016年11月 ポスター発表
• Characteristic for biotransformation of polychrolinated biphenyls in cats.  [通常講演]

  Hazuki Mizukawa, Misaki Maehara, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Kei Nomiyama, Hiroyuki Nishikawa, Yoshinori Ikenaka, Shouta M.M. Nakayama, Kohki Takaguchi, Shinsuke Tanabe, Mayumi Ishizuka

  The 7th SETAC World Congress/37th SETAC North America Annual Meeting 2016年11月 ポスター発表
• Genetic effects of the pesticide DDT on birds: lessons learned from a field study in South Africa  [通常講演]

  Lesa Thompson, Yoshinori Ikenaka, Yared Yohannes, Toshio Tsubota, Johan van Vuren, Victor Wepener, Nico Smit, Shouta Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  The 9th International Meeting of the Asian Society of Conservation Medicine (ASCM) "One Health in Asia-Pacific" 2016年10月 口頭発表（一般）
• In vivo analysis of PCB metabolic capacities and effects on the thyroid hormone in cats.  [通常講演]

  Hazuki, Mizukawa, Misaki Maehara, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Kei Nomiyama, Hiroyuki Nishikawa, Kohki Takaguchi, Aksorn Saengtienchai, Tsend-ayush Sainnoxoi, Yoshinori Ikenaka, Shouta M.M. Nakayama, Shinsuke Tanabe, Mayumi Ishizuka

  The 9th International PCB Workshop 2016年10月 口頭発表（一般）
• 野生げっ歯類の殺鼠剤の抵抗性メカニズムと非対象動物に対する毒性メカニズム  [通常講演]

  石塚真由美, 中山翔太, 水川葉月, 池中良徳

  日本哺乳類学会2016年度大会「企画シンポジウム：野生動物が関わる問題にどのように対応するか？〜基礎研究を応用した解決への取り組み〜」 2016年09月 口頭発表（一般）
• Playing "chicken" - a xenobiotic dilemma  [通常講演]

  Lesa THOMPSON, Yoshinori IKENAKA, Yared YOHANNES, Atnafu ASSEFA, Johan VAN VUREN, Victor WEPENER, Nico SMIT, Wynand VLOK, Shouta NAKAYAMA, Hazuki MIZUKAWA, Mayumi ISHIZUKA

  The 4th Sapporo Summer Seminar for One Health (SaSSOH) 2016年09月 口頭発表（一般）
• The effect of environmental pollutants to pet animals ~Level and effects of Persistent organic pollutants (POPs) to domestic cat~.  [通常講演]

  Tsend-ayush Sainnokhoi, Hazuki Mizukawa, Misaki Maehara, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Kei Nomiyama, Aksorn Saengtienchai, Shinsuke Tanabe, Yoshinori Ikenaka, Shouta M.M. Nakayama, Mayumi Ishizuka

  The 4th Sapporo Summer Seminar for One Health (SaSSOH) 2016年09月 口頭発表（一般）
• A glycomics approach to renal biomarkers in birds.  [通常講演]

  Chihiro Ishii, Yoshinori Ikenaka, Osamu Ichii, Shouta M.M. Nakayama, Hazuki Mizukawa, Shin-Ichiro Nishimura, Tetsu Ohashi, Masakazu Tanaka, Keisuke Saito, Yukiko Watanabe, Mayumi Ishizuka

  The 4th Sapporo Summer Seminar for One Health (SaSSOH) 2016年09月 口頭発表（一般）
• Lead exposure on human samples in African countries and lead pollution in Kabwe, Zambia.  [通常講演]

  Haruya Toyomaki, Shouta M.M. Nakayama, Yared B. Yohannes, John Yabe, Kaampwe Muzandu, Hazuki Mizukawa, Yoshinori Ikenaka, Mayumi Ishizuka

  The 4th Sapporo Summer Seminar for One Health (SaSSOH) 2016年09月 口頭発表（一般）
• Investigation of Warfarin Metabolic Ability of Warfarin Resistant Roof Rats by in situ Liver Perfusion.  [通常講演]

  Kazuki Takeda, Yoshinori Ikenaka, Tsutomu Tanikawa, Kazuyuki D. Tanaka, Shouta M.M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  The 4th Sapporo Summer Seminar for One Health (SaSSOH) 2016年09月 ポスター発表
• UGT2Bサブファミリーに着目した食肉目におけるグルクロン酸抱合能の動物種差解明  [通常講演]

  近藤誉充, 池中良徳, 中山翔太, 水川葉月, Aksorn Saengtienchai, Yared Beyene, 坂本健太郎, 和田昭彦, 服部薫, 三谷曜子, 田辺信介, 野見山桂, 石塚真由美

  平成28年度内外環境応答・代謝酵素研究会 2016年09月 口頭発表（一般）
• 鳥類におけるグルクロン酸抱合酵素による薬物代謝  [通常講演]

  新屋惣, 池中良徳, 中山翔太, 石井千尋, 水川葉月, 齊藤慶輔, 渡邉有希子, 伊藤真輝, 高江洲昇, 坂本健太郎, 石塚真由美

  第22回日本野生動物医学会 2016年09月 口頭発表（一般）
• 鳥類における新規腎障害マーカーの探索  [通常講演]

  石井千尋, 池中良徳, 市居修, 中山翔太, 西村紳一郎, 大橋哲, 田中誠一, 齊藤慶輔, 渡邊有希子, 水川葉月, 石塚真由美

  第22回日本野生動物医学会 2016年09月 ポスター発表
• 家畜・家禽の鉛安定同位体生体内分別の種差および歩哨動物としての有用性評価  [通常講演]

  栂尾正雄, 中山翔太, John Yabe, 池中良徳, 中田北斗, 石井千尋, 水川葉月, Yared B. Yohannes, Aksorn Saengtienchai, 石塚真由美

  第159回日本獣医学会学術集会 2016年09月 口頭発表（一般）
• 野生動物及び実験動物におけるグルクロン酸抱合酵素の動物種差解明  [通常講演]

  近藤誉充, 池中良徳, 中山翔太, 水川葉月, Aksorn Saengtienchai, Yared Beyene, 坂本健太郎, 和田昭彦, 服部薫, 三谷曜子, 田辺信介, 野見山桂, 石塚真由美

  第159回日本獣医学会学術集会 2016年09月 口頭発表（一般）
• Pharmacokinetic analysis of warfarin resistant roof rats (Rattus rattus) in Tokyo  [通常講演]

  Kazuki Takeda, Yoshinori Ikenaka, Tsutomu Tanikawa, Kazuyuki D. Tanaka, Shouta M.M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  8th International Toxicology Symposium in Africa 2016年08月 ポスター発表
• Is there species difference of biological variation of lead (Pb) isotopic composition between livestock and poultry?  [通常講演]

  Masao Togao, Shouta M.M, Nakayama, John Yabe, Hokuto Nakata, Yoshinori Ikenaka, Chihiro Ishii, Yared B. Yohannes, Hazuki Mizukawa, Wageh Sobhy Darwish, Aksorn Saengtienchai, Mayumi Ishizuka

  8th International Toxicology Symposium in Africa 2016年08月 ポスター発表
• Metabolic capacities of polychlorinated biphenyls (PCBs) in cats and dogs  [通常講演]

  Hazuki Mizukawa, Kei Nomiyama, Shinsuke Tanabe, Misaki Maehara, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Yoshinori Ikenaka, Shouta M.M. Nakayama, Mayumi Ishizuka

  8th International Toxicology Symposium in Africa 2016年08月 ポスター発表
• Pb levels and isotope ratio profiles in kidneys of Japanese wild rats  [通常講演]

  Shouta M.M. Nakayama, Hokuto Nakata, Balazs Oroszlany, Yoshinori Ikenaka, Hazuki Mizukawa, Kazuyuki Tanaka, Tsunehito Harunari, Tsutomu Tanikawa, Yared B. Yohannes, Aksorn Saengtienchai, Mayumi Ishizuka

  8th International Toxicology Symposium in Africa 2016年08月 ポスター発表
• Cytochrome P450 expression in the rabbit  [通常講演]

  Walaa Fathy Saad Eldin, Wageh S. Darwish, Yoshinori Ikenaka, Shouta M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  8th International Toxicology Symposium in Africa 2016年08月 ポスター発表
• Creating a model of renal damage in chicken and glycomic approach to identify novel biomarkers for kidney injury in birds  [通常講演]

  Chihiro Ishii, Yoshinori Ikenaka, Osamu Ichii, Shouta M.M. Nakayama, Shin-Ichiro Nishimura, Tetsu Ohashi, Masakazu Tanaka, Keisuke Saito, Yukiko Watanabe, Hazuki Mizukawa, Mayumi Ishizuka

  8th International Toxicology Symposium in Africa 2016年08月 口頭発表（一般）
• Risk Assessment of Heavy Metals via Consumption of Muscle and Offal of Free-Range Animals from Benin City  [通常講演]

  Emmanuel Temiotan, Ogbomida, Shouta M.M. Nakayama, Nesta Bortey-Sam, Balazs Oroszlany, Isioma Tongo, Alex Ajeh Enuneku, Ogbeide Ozekeke, Martins Oshioriamhe Ainerua, Iriagbonse Priscillia Fasipe, Lawrence Ikechukwu Ezemonye, Hazuki Mizukawa, Yoshinori Ikenaka, Mayumi Ishizuka

  8th International Toxicology Symposium in Africa 2016年08月 口頭発表（一般）
• Lead exposure on human samples in African countries: a mini review  [通常講演]

  Haruya Toyomaki, Shouta M.M. Nakayama, Yared B. Yohannes, Hazuki Mizukawa, Yoshinori Ikenaka, Mayumi Ishizuka

  8th International Toxicology Symposium in Africa 2016年08月 口頭発表（一般）
• Kabwe childhood lead poisoning: past, present and future  [通常講演]

  John Yabe, Shouta MM Nakayama, Yoshinori Ikenaka, Yared B. Yohannes, Haruya Toyomaki, Kennedy Choongo, Kaampwe Muzandu, Mayumi Ishizuka

  8th International Toxicology Symposium in Africa 2016年08月 口頭発表（一般）
• Metal pollution problems in animals and children in Kabwe mining area, Republic of Zambia- Source Estimation by Stable Pb isotopes-  [招待講演]

  中山翔太

  第16回北大若手研究者交流会 2016年08月 口頭発表（招待・特別）
• 本当にソノポレーションか？  [通常講演]

  佐々木東, 工藤信樹, 中山翔太, 滝口満喜

  平成28年度 第2回 光超音波画像研究会 2016年08月 口頭発表（一般）
• N-glycans as potential novel biomarkers for kidney injury in avian species.  [通常講演]

  Chihiro Ishii, Yoshinori Ikenaka, Osamu Ichii, Shouta M.M, Nakayama, Hazuki Mizukawa, Shin-Ichiro Nishimura, Tetsu Ohashi, Masakazu Tanaka, Keisuke Saito, Yukiko Watanabe, Mayumi Ishizuka

  65th International Conference of the Wildlife Disease Association, 2016年07月 ポスター発表
• Human health risk due to polycyclic aromatic hydrocarbon (PAHs) exposure in Kumasi, Ghana; and excretion of PAH metabolites in cattle urine from urban and rural sites.  [通常講演]

  Nesta Bortey-Sam, Yoshinori Ikenaka, Shouta M.M. Nakayama, Aksorn Saengtienchai, Hazuki Mizukawa, Mayumi Ishizuka

  第30回北海道薬物作用談話会 2016年07月 口頭発表（一般）
• KAMPAI -Team 2, PAST, PRESENT and FUTURE-  [通常講演]

  Shouta M.M, Nakayama, John Yabe, Yared Beyene, Haruya Toyomaki, Kaampwe Muzandu, Kennedy Choongo, Hazuki Mizukawa, Yoshinori Ikenaka, Mayumi Ishizuka

  Kick-Off Symposium for the “The Project for Visualization of impact of chronic/latent chemical hazard and Geo-Ecological Remediation in Zambia” 2016年07月 口頭発表（一般）
• UGTの動物種差  [通常講演]

  石塚 真由美, 中山 翔太, 水川 葉月, 池中 良徳

  第43回日本毒性学会学術年会 2016年06月 口頭発表（一般）
• ポリ塩化ビフェニル（PCBs）のin vivo暴露によるネコの異物代謝解明と甲状腺ホルモンへの影響評価  [通常講演]

  水川 葉月, 前原 美咲, 横山 望, 市居 修, 滝口 満喜, 野見山 桂, 西川 博之, 池中 良徳, 中山 翔太, 高口 倖暉, 田辺 信介, 石塚 真由美

  第43回日本毒性学会学術年会 2016年06月 口頭発表（一般）
• ハリネズミは化学物質高感受性種？ African hedgehog (Atalerix albiventris)で観察された低薬物代謝能  [通常講演]

  アクソルン サエンティエンチャイ, 池中 良徳, ネスタ サム, ウスマ ジャムナーク, 水川 葉月, 中山 翔太, 石塚 真由美

  第43回日本毒性学会学術年会 2016年06月 ポスター発表
• 東京由来ワルファリン抵抗性クマネズミクローズドコロニーでのワルファリン体内動態の解明  [通常講演]

  武田一貴, 池中良徳, 田中和之, 谷川力, 中山翔太, 水川葉月, 石塚真由美

  第43回日本毒性学会学術年会 2016年06月 口頭発表（一般）
• 脂肪組織における芳香族炭化水素受容体(AhR)の機能解明  [通常講演]

  本平 航大, 池中 良徳, ワギ ダルウィシュ, 中山 翔太, 水川 葉月, 石塚 真由美

  第43回日本毒性学会学術年会 2016年06月 口頭発表（一般）
• Contamination of eggs from free-ranging chickens in a malaria-endemic region using DDT as vector control  [通常講演]

  Lesa Thompson, Yoshinori Ikenaka, Yared Yohannes, Johan van Vuren, Victor Wepener, Nico Smit, Wynand Vlok, Shouta Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  International Society for Environmental Epidemiology-International Society of Exposure Sciences Asia Chapter (ISEE-ISES AC) 2016 2016年06月 口頭発表（一般）
• メタボローム解析を用いたPCBsによるイエネコの毒性影響評価  [通常講演]

  西川博之, 野見山桂, 水川葉月, 横山望, 市居修, 滝口満喜, 石塚真由美, 池中良徳, 中山翔太, 江口哲史, 国末達也, 田辺信介

  第25回環境化学討論会 2016年06月 口頭発表（一般）
• 有機ハロゲン化合物によるコンパニオンアニマルの汚染実態と甲状腺ホルモンへの影響評価  [通常講演]

  野見山 桂, 山本 恭央, 水川 葉月, 江口 哲史, 滝口 満喜, 中山 翔太, 池中 良徳, 石塚 真由美, 国末 達也, 田辺 信介

  第25回環境化学討論会 2016年06月 口頭発表（一般）
• ヒト尿中のネオニコチノイドおよびその代謝産物の分析法の確立とヒトへの曝露評価  [通常講演]

  池中 良徳, 藤岡 一俊, 平 久美子, 中山 翔太, 水川 葉月, 一瀬 貴大, Jemima Tiwaa Marfo, 有薗 幸司, 加藤 恵介, 石坂 真澄, 馬場 浩司, 川上 智規, 石塚 真由美

  第25回環境化学討論会 2016年06月 口頭発表（一般）
• ネコにおけるポリ塩化ビフェニル（PCBs）の異物代謝機構解明と甲状腺ホルモンへの影響評価  [通常講演]

  水川葉月, 前原美咲, 横山望, 市居修, 滝口満喜, 野見山桂, 西川博之, 池中良徳, 中山翔太, 高口倖暉, 田辺信介, 石塚真由美

  第25回環境化学討論会 2016年06月 口頭発表（一般）
• Plasma essential trace element concentrations in dogs with chronic enteropathy.  [通常講演]

  Nozomu Yokoyama, Hiroshi Ohta, Hazuki Mizukawa, Yumiko Kagawa, Shouta Nakayama, Noboru Sasaki, Keitaro Morishita, Kensuke Nakamura, Yoshinori Ikenaka, Mayumi Ishizuka, Mitsuyoshi Takiguchi

  American College of Veterinary Internal Medicine Forum 2016 2016年06月 口頭発表（一般）
• Human health risk due to polycyclic aromatic hydrocarbon (PAHs) exposure in Kumasi, Ghana; and excretion of PAH metabolites in cattle urine from urban and rural sites.  [通常講演]

  Nesta Bortey-Sam, Yoshinori Ikenaka, Osei Akoto, Shouta M.M. Nakayama, Kwadwo A. Asante, Christian Obirikorang, Elvis Baidoo, Aksorn Saengtienchai, Hazuki Mizukawa, Mayumi Ishizuka

  SETAC Europe 26th Annual Meeting 2016年05月 ポスター発表
• Risk versus benefits of controlling vector-borne diseases using insecticides: a case example in South Africa  [通常講演]

  L A Thompson, Y Ikenaka, Y B Yohannes, J J van Vuren, V Wepener, N J Smit, W Vlok, S M M Nakayama, H Mizukawa, M Ishizuka

  2nd International Conference on One Medicine One Science (iCOMOS) 2016年04月 ポスター発表
• 非実験動物における化学物質代謝能の特徴と種差  [通常講演]

  池中良徳, 筧麻友, 水川葉月, 中山翔太, 石塚真由美

  日本薬学会第136年会（横浜） 2016年03月 口頭発表（一般）
• TOXICOLOGICAL ASSESSMENT OF PCBS AND OH-PCBS IN CAT USING METABOLOMICS APPROACH  [通常講演]

  Hiroyuki Nishikawa, Kei Nomiyama, Akifumi Eguchi, Hazuki Mizukawa, Mayumi Ishizuka, Yoshinori Ikenaka, Shouta M, M. Nakayama, Shinsuke Tanabe

  INTERNATIONAL SYMPOSIUM ON ENVIRONMENTAL CHEMISTRY AND TOXICOLOGY ? TO ACCELERATE A GLOBAL NETWORK OF ENVIRONMENTAL RESEARCHERS 2016年03月 ポスター発表
• BIOTRANSFORMATION POTENCIES OF POLYCHLORINATED BIPHENYLS IN CATS  [通常講演]

  Hazuki Mizukawa, Misaki Maehara, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Kei Nomiyama, Yoshinori Ikenaka, Shouta M.M.Nakayama, Shinsuke Tanabe, Mayumi Ishizuka

  INTERNATIONAL SYMPOSIUM ON ENVIRONMENTAL CHEMISTRY AND TOXICOLOGY ? TO ACCELERATE A GLOBAL NETWORK OF ENVIRONMENTAL RESEARCHERS 2016年03月 ポスター発表
• 犬の慢性腸症における血中微量元素プロファイルの解析  [通常講演]

  横山 望, 大田 寛, 水川 葉月, 賀川 由美子, 中山 翔太, 佐々木 東, 森下 啓太郎, 中村 健介, 池中 良徳, 石塚 真由美, 滝口 満喜

  第12回日本内科学アカデミー学術集会 2016年02月 口頭発表（一般）
• racing migration of northern fur seals in Russian-Japanese waters using stable isotopes in whiskers  [通常講演]

  Ayako Yamada, Takanori Horimoto, Yoshinori Ikenaka, Shouta M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka, Yoko Mitani, Kazushi Miyashita

  21st Biennial Conference on Marine Mammals 2015年12月 ポスター発表
• Diet records in winter, migration and diving behavior during early summer of juvenile Steller sea lions in the asian stock  [通常講演]

  Keizo Ito, Nao Takahashi, Kaoru Hattori, Yoko Goto, Takuya Nakanowatari, Kay I. Ohshima, Takanori Horimoto, Yoshinori Ikenaka, Shouta M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka, Kazushi Miyashita, Yoko Mitani

  21st Biennial Conference on Marine Mammals 2015年12月 ポスター発表
• The habitat use of northern fur seals Callorhinus ursinus around northern Japan during non-breeding season, defined from stable isotopes and trace elements in whiskers  [通常講演]

  Takanori Horimoto, Svetlana Artemyeva, Peter Permyakov, Mari Kobayashi, Kaoru Hattori, Hiromi Kasai, Hiroshige Tanaka, Yoshinori Ikenaka, Shouta M, M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka, Vladimir Burkanov, Russel Andrews, Yoko Mitani, Yasunori Sakurai

  21st Biennial Conference on Marine Mammals 2015年12月 ポスター発表
• Metabolism and biotransformation of organohalogen compounds in the liver microsomes of cats and dogs  [通常講演]

  Hazuki Mizukawa, Kei Nomiyama, Nozomu, Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Yoshinori Ikenaka, Shouta M.M, Nakayama, Misaki Maehara, Shinsuke Tanabe, Mayumi Ishizuka

  SETAC North America 36th Annual Meeting 2015年11月 ポスター発表
• Vector-control pesticide DDT detected in free-ranging chickens from South Africa  [通常講演]

  Lesa A THOMPSON, Yoshinori IKENAKA, Yared B YOHANNES, Johan J, VAN VUREN, Victor WEPENER, Nico J SMIT, Wynand VLOK, Shouta M M NAKAYAMA, Hazuki MIZUKAWA, Mayumi ISHIZUKA

  The 3rd Sapporo Summer Seminar for One Health (SaSSOH) 2015年09月 ポスター発表
• カブエ鉱床地域における鉛汚染とリモートセンシングを活用した今後の研究展望  [通常講演]

  中山翔太

  第五回超小型衛星に関する勉強会 2015年09月 口頭発表（一般）
• 抗血液凝固系殺鼠剤の標的分子であるビタミンKエポキシド還元酵素(VKOR)の鳥類における特徴及び種差  [通常講演]

  森田鮎子, 池中良徳, 中山翔太, 石井千尋, 水川葉月, 渡邉研右, 齊藤慶輔, 渡邊有希子, 伊藤真輝, 高江洲昇, 石塚真由美

  第158回日本獣医学会学術集会 2015年09月 口頭発表（一般）
• Exposure levels of polycyclic aromatic hydrocarbons (PAHs) and heavy metals in wild rats in Kumasi, Ghana  [通常講演]

  Nesta Bortey-Sam, Yoshinori Ikenaka, Osei Akoto, Shouta M.M. Nakayama, Yared Beyene Yohannes, Elvis Baidoo, Aksorn Saengtienchai, Hazuki Mizukawa, Mayumi Ishizuka

  7th International Toxicology Symposium in Africa 2015年08月 口頭発表（一般）
• Assessment of exposure to toxic elements (As, Pb, Cd and Hg), and DDTs in four species of birds from Ethiopia  [通常講演]

  Yared Beyene Yohannes, Yoshinori Ikenaka, Shouta MM. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  7th International Toxicology Symposium in Africa 2015年08月 口頭発表（一般）
• HCH’s in two fish species from a large floodplain pan within a subtropical conservation area  [通常講演]

  Clare Edwards, Yoshinori Ikenaka, Yared Beyene, Shouta MM. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka, Victor Wepener, Johan, H.J. van Vuren

  7th International Toxicology Symposium in Africa 2015年08月 口頭発表（一般）
• Histopathologic assessment of co-joint Cd and Pb exposure in rats  [通常講演]

  ohn Yabe, Yoshinori Ikenaka, Shouta MM Nakayama, Wageh Sobhy Darwish, Nesta Bortey-Sam, Yared B. Yohannes, Aksorn Saengtienchai, Andy Saengtienchai, Takashi Umemura, Mayumi Ishizuka

  7th International Toxicology Symposium in Africa 2015年08月 口頭発表（一般）
• Metallothionein as a biomarker for chicken exposure to heavy metals  [通常講演]

  Wageh S. Darwish, Walaa F, Saad Eldin, Nesta Bortey-Sam, Yoshinori Ikenaka, Shouta M.M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  7th International Toxicology Symposium in Africa 2015年08月 口頭発表（一般）
• Lead pollution in the children in Kabwe mining area, Republic of Zambia- Source identification by stable isotope analysis  [通常講演]

  Shouta M M, Nakayama, John Yabe, Yoshinori Ikenaka, Yared Beyene Yohannes, Balazs Oroszlany, Nesta Bortey-Sam, Kaampwe Muzandu, Hazuki Mizukawa, Kenedy Choongo, Abel Kabalo, Aaron Mweene, Mayumi Ishizuka

  7th International Toxicology Symposium in Africa 2015年08月 口頭発表（一般）
• Vector-control pesticide DDT detected in free-ranging chickens from South Africa  [通常講演]

  Lesa A Thompson, Yoshinori Ikenaka, Yared B Yohannes, Johan van Vuren, Victor Wepener, Nico J Smit, Wynand Vlok, Shouta M M Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  7th International Toxicology Symposium in Africa 2015年08月 口頭発表（一般）
• Accumulation Patterns and Risk Assessment of Metals and Metalloids in Muscle and Offal of free Range Chickens (Gallus gallus domesticus), Cattle (Bos taurus) and Goat (Capra hircus) in Benin City  [通常講演]

  Ogbomida, E.T, Nakayama S.M.M, Bortey-Sam N, Oroszlany, B, Tongo I, Enuneku A.A, Ogbeide O, Oshioriamhe M.A, Fasipe, P.I, Ezemonye L.I.N, Mizukawa H, Ikenaka Y, Ishizuka M

  7th SETAC Africa Conference 2015年08月 口頭発表（一般）
• Phase II xenobiotic metabolizm in carnivora -UGT activity and genomestructure in Pinniped species-  [通常講演]

  Yoshinori Ikenaka, Mayu Kakehi, Shouta Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  7th SETAC Africa Conference 2015年08月 口頭発表（一般）
• シンポジウム「野生鳥類の化学物質汚染とその影響」鳥類で起こっているケミカルハザードとそのメカニズム  [招待講演]

  中山翔太, 水川葉月, 池中良徳, 石塚真由美

  第21回日本野生動物医学会大会 2015年07月 口頭発表（招待・特別）
• 北海道沿岸にストランディングした鯨類の臓器における金属濃度の測定とその比較検討  [通常講演]

  川田大紀, 松田純佳, 松石隆, 中山翔太, 石塚真由美, 浅川満彦, 能田淳

  第21回日本野生動物医学会大会 2015年07月 ポスター発表
• Protective Effects of Carotenoids and Retinoids on Benzo[a]Pyrene Induced Mutagenicity and Oxidative Stress  [通常講演]

  Wageh Sobhy Darwish, Yoshinori Ikenaka, Shouta M.M, Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  42nd Annual Meeting of the Japanese Society of Toxicology (42JSOT) 2015年06月 口頭発表（一般）
• Vector-control pesticides disseminating via international waterways to accumulate in free-ranging freshwater and marine fish species  [通常講演]

  Lesa A Thompson, Yoshinori Ikenaka, Johannes J, van Vuren, Victor, Wepener, Nico Smit, Wynand Vlok, Yared B. Yohannes, Hazuki Mizukawa, Shouta M.M. Nakayama, Mayumi Ishizuka

  Vth International Wildlife Management Congress 2015 2015年06月 ポスター発表
• Lead poisoning and source identification in raptors from Japan  [通常講演]

  Chihiro Ishii, Shouta M.M. Nakayama, Yoshinori Ikenaka, Hazuki Mizukawa, Yared B. Yohannes, Hokuto Nakata, Keisuke Saito, Yukiko Watanabe, Shinsuke Tanabe, Kei Nomiyama, Terutake Hayashi, Yasushi Masuda, Kentaro, Q. Sakamoto, Mayumi Ishizuka

  Vth International Wildlife Management Congress 2015 2015年06月 口頭発表（一般）
• 渡り性海鳥2種の越冬海域と羽の水銀濃度  [通常講演]

  綿貫豊, 山下愛, 石塚真由美, 池中良徳, 中山翔太, 石井千尋, 山本誉士, 伊藤元裕, 桑江 朝比呂, 鈴木裕也, 新妻靖彰, C.E. Meathrel, P.N. Trathan, R.A. Phillips

  第24回環境化学討論会 2015年06月 ポスター発表
• タンチョウの水銀蓄積特性に関する検討  [通常講演]

  寺岡宏樹, 岡本絵梨佳, 久道萌, 中山翔太, 池中良徳, 石塚真由美, 北澤多喜雄

  第24回環境化学討論会 2015年06月 ポスター発表
• ウマにおけるシトクロムP450の特性評価：ジアゼパム代謝を担うCYP3Aの重要性  [通常講演]

  水川葉月, 中山翔太, 池中良徳, 速水秋, Wageh Sobhy Darwish, 渡邊研右, 川合佑典, 石塚真由美

  第24回環境化学討論会 2015年06月 ポスター発表
• 第II相抱合反応の種差：食肉目におけるグルクロン酸抱合酵素の進化と遺伝子構造  [通常講演]

  池中良徳, 筧麻友, 中山翔太, 川合佑典, 渡邊研右, 水川葉月, 野見山桂, 田辺信介, 石塚真由美

  第24回環境化学討論会 2015年06月 口頭発表（一般）
• Vector-controlling pesticides in free-ranging chickens in KwaZulu-Natal, South Africa  [通常講演]

  Lesa A Thompson, Yoshinori Ikenaka, Johannes J, van Vuren, Victor, Wepener, Nico Smit, Wynand Vlok, Yared B Yohannes, Hazuki Mizukawa, Shouta M, M. Nakayama, Mayumi Ishizuka

  第24回環境化学討論会 2015年06月 口頭発表（一般）
• Victor Wepener, Insights into sub-tropical lowland river food webs using stable isotopes  [通常講演]

  Ruan Gerber, Nico J. Smit, Johan, H.J. Van Vuren, Shouta M.M. Nakayama, Yoshinori Ikenaka, Mayumi Ishizuka, Victor Wepener

  第24回環境化学討論会 2015年06月 口頭発表（一般）
• Nitrate content in Egyptian meat products and its modulatory effects on xenobiotic metabolizing enzymes  [通常講演]

  Wageh Sobhy Darwish, Mohamed Abdallah Hussein, Yoshinori Ikenaka, Shouta M.M, Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  第24回環境化学討論会 2015年06月 口頭発表（一般）
• Concentrations of polycyclic aromatic hydrocarbon metabolites (OH-PAHs) in domestic animal in Kumasi, Ghana  [通常講演]

  Nesta Bortey-Sam, Yoshinori Ikenaka, Osei Akoto, Shouta M.M. Nakayama, Jemima Marfo, Hazuki Mizukawa, Mayumi Ishizuka

  第24回環境化学討論会 2015年06月 口頭発表（一般）
• 野生齧歯類におけるワルファリン抵抗性獲得機序の解明  [通常講演]

  武田一貴, 池中良徳, 田中和之, 中山翔太, 谷川力, 水川葉月, 石塚真由美

  第24回環境化学討論会 2015年06月 口頭発表（一般）
• 猛禽類における鉛中毒問題と骨における鉛分布の解明  [通常講演]

  石井千尋, 中山翔太, 池中良徳, 水川葉月, 中田北斗, 森田鮎子, 齊藤慶輔, 渡邊有希子, 神和夫, 田辺信介, 野見山桂, 林光武, 増田泰, 坂本健太郎, 石塚真由美

  第24回環境化学討論会 2015年06月 口頭発表（一般）
• Lead (Pb) poisoning in children from townships around an extensive lead-zinc mine in Kabwe, the Republic of Zambia  [通常講演]

  Shouta M.M, Nakayama, John Yabe, Yoshinori Ikenaka, Yared Beyene, Nesta Bortey-Sam, Balazs Oroszlany, Kaampwe Muzandu, Kennedy Choongo, Aaron Mweene, Abel Kabalo, Hazuki Mizukawa, Mayumi Ishizuka

  日本地球惑星科学連合2015年大会 2015年05月 口頭発表（一般）
• 日本海北部に来遊するキタオットセイ の安定同位体比と利用海域の関係  [通常講演]

  山田綾子, 堀本高矩, 石塚真由美, 池中良徳, 中山翔太, 水川葉月, 三谷曜子, 宮下和士

  平成27年度日本水産学会秋季大会 2015年03月 口頭発表（一般）
• High concentration of Pb in soil, domestic animals and children from townships near a lead-zinc mine in Kabwe  [招待講演]

  Shouta M.M, Nakayama, John Yabe, Yoshinori Ikenaka, Kaampwe Muzandu, Kennedy Choongo, Mayumi Ishizuka

  Workshop on Mining and the Environment 2015年03月 口頭発表（招待・特別）
• 外来化学物質の代謝の種差  [招待講演]

  石塚真由美, 中山翔太, 水川葉月, 池中良徳

  第31回日本毒性病理学シンポジウム「毒性病理学と獣医病理学を繋ぐ比較の生物学−共通性と種差を知ろう」 2015年01月 口頭発表（招待・特別）
• 食肉目におけるグルクロン酸抱合酵素の遺伝子解析  [通常講演]

  筧麻友, 池中良徳, 中山翔太, 水川葉月, 渡邉研右, 坂本健太郎, 和田 昭彦, 服部薫, 田辺信介, 野見山桂, 石塚真由美

  第37回日本分子生物学会年会 2014年11月 ポスター発表
• Distribution of toxic metals in free-range chicken, goat and sheep in Ghana and other African countries; and assessment of potential risks to human health through consumption  [通常講演]

  Nesta Bortey-Sam, Shouta M.M. Nakayama, Yoshinori Ikenaka, Yared Beyene Yohannes, Elvis Baidoo, Hazuki Mizukawa, Osei Akoto, Mayumi Ishizuka

  SETAC North America 35th Annual Meeting 2014年11月 ポスター発表
• Species differences of UDP-glucuronosyltransferases (UGTs) in Carnivores  [通常講演]

  Mayu Kakehi, Yoshinori Ikenaka, Shouta MM Nakayama, Hazuki Mizukawa, Kensuke P, Watanabe, Kentaro Sakamoto, Akihiko Wada, Kaoru Hattori, Shinsuke Tanabe, Kei Nomiyama, Mayumi Ishizuka

  12th International Symposium on Cytochrome P450 Biodiversity and Biotechnology 2014年09月 ポスター発表
• Mammalian interspecies differences in xenobiotic phase II reaction  [招待講演]

  Yoshinori Ikenaka, Saengtienchai Aksorn, Mayu Kakehi, Shouta M.M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka

  12th International Symposium on Cytochrome P450 Biodiversity and Biotechnology 2014年09月 口頭発表（招待・特別）
• Contamination status and biotransformation of organohalogen compounds in cats and dogs  [通常講演]

  Hazuki Mizukawa, Kei Nomiyama, Susumu Nakatsu, Akira Kubota, Hisato Iwata, Yoshinori Ikenaka, Shouta M.M. Nakayama, Shinsuke Tanabe, Mayumi Ishizuka

  12th International Symposium on Cytochrome P450 Biodiversity and Biotechnology 2014年09月 ポスター発表
• 鰭脚類においてグルクロン酸抱合酵素が担う異物代謝  [通常講演]

  筧麻友, 池中良徳, 中山翔太, 水川葉月, 渡邉研右, 坂本健太郎, 和田 昭彦, 服部薫, 田辺信介, 野見山桂, 石塚真由美

  第20回日本野生動物医学会つくば大会 2014年09月 ポスター発表
• ニワトリにおけるDDTの汚染状況と臓器蓄積性の解析  [通常講演]

  伊藤玄悟, 池中良徳, Beyene Yared, 中山翔太, 水川葉月, Vuren Johannes, Wepener Victor, Smit Nico, ynand Vlok, 石塚真由美

  第157回日本獣医学会学術集会 2014年09月 口頭発表（一般）
• 日本における猛禽類の鉛中毒被害状況と中毒原因、鉛体内分布の解明  [通常講演]

  石井千尋, 中山翔太, 池中良徳, 水川葉月, 中田北斗, 齊藤慶輔, 渡邊有希子, 田辺信介, 野見山桂, 林光武, 増田泰, 坂本健太郎, 石塚真由美

  第157回日本獣医学会学術集会 2014年09月 口頭発表（一般）
• アフリカのゴミ集積場における化学物質の汚染実態と生体への健康影響の評価：ナイロビのダンドラ地域における家畜の重金属汚染の例  [通常講演]

  中田北斗, 中山翔太, 水川葉月, 池中良徳, 石井千尋, ヨハンネス ヤレド, ベイヤネ, ヤベジョン, 今内覚, 石塚真由美

  第157回日本獣医学会学術集会 2014年09月 口頭発表（一般）
• The impact of environmental stressors on biomarkers in Clarias gariepinus and Oreochromis mossambicus in Ndumo game reserve  [通常講演]

  Mary Tsono Mkhonto, Johan J, van Vuren, Nico Smit, Yoshinori Ikenaka, Shouta M.M. Nakayama, Hazuki Mizukawa, Yared Beyene Yohannes, Mayumi Ishizuka

  6th International Toxicology Symposium in Africa 2014年08月 口頭発表（一般）
• Antibiotics residues in different poultry meats marketed in Egypt  [通常講演]

  Wageh Sobhy Darwish, Yoshinori Ikenaka, Shouta Nakayama, Mayumi Ishizuka, Eldaly Elsaid, El-Abbasy Mohamed, El-Ghareeb Walid, Tharwat Ahmed, El-Desoky Kamal, Elged Mohamed

  6th International Toxicology Symposium in Africa 2014年08月 口頭発表（一般）
• Biomarkers of pollution in Synodontis zambesensis and Hydrocynus vittatus in the lower Pongola river and floodplain  [通常講演]

  Claire Michelle Edwards, Yoshinori Ikenaka, Yared Beyene Yohannes, Shouta M.M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka, Victor Wepener, Johan J, van Vuren

  6th International Toxicology Symposium in Africa 2014年08月 口頭発表（一般）
• Aquatic toxicology of gold nanoparticles (nAu) in Danio rerio  [通常講演]

  Tarryn Lee Botha, Yoshinori Ikenaka, Shouta M.M. Nakayama, Mayumi Ishizuka, Victor Wepener

  6th International Toxicology Symposium in Africa 2014年08月 口頭発表（一般）
• Comparison of the Olifants and Luvuvhu river aquatic food webs, potential food web disturbances and dietary patterns of Hydrocynus vittatus as revealed by stable isotope analyses  [通常講演]

  Ruan Gerber, Victor Wepener, Johan J, van Vuren, Shouta M.M. Nakayama, Yoshinori Ikenaka, Mayumi Ishizuka, Nico Smit

  6th International Toxicology Symposium in Africa 2014年08月 口頭発表（一般）
• Distribution of heavy metals in organs of sheep and goat reared in Obuasi, a gold mining town in Ghana  [通常講演]

  Osei Akoto, Nesta Bortey-Sam, Shouta M.M. Nakayama, Yoshinori Ikenaka, Elvis Baidoo, Yared Beyene Yohannes, Hazuki Mizukawa, Mayumi Ishizuka

  6th International Toxicology Symposium in Africa 2014年08月 口頭発表（一般）
• Health Risk Assessment of Heavy Metal Residues in Tissues of Cattle and Goats in Benin City, Nigeria  [通常講演]

  Emmanuel Temiotan, Ogbomida, Isioma Tongo, Alex Ajeh Enuneku, Martins Oshioriamhe Ainerua, Shouta M.M. Nakayama, Nesta Bortey-Sam, Balazs Oroszlany, Lawrence Ikechukwu Ezemonye, Mayumi Ishizuka

  6th International Toxicology Symposium in Africa 2014年08月 口頭発表（一般）
• Pb excretion in feces and urine of exposed children from polluted townships in Kabwe, Zambia  [通常講演]

  John Yabe, Shouta M.M. Nakayama, Yoshinori Ikenaka, Yared B Yohannes, Nesta Bortey-Sam, Balazs Oroszlany, Kaampwe Muzandu, Kennedy Choongo, Abel Nketani Kabalo, John Ntapisha, Aaron Mweene, Takashi Umemura, Mayumi Ishizuka

  6th International Toxicology Symposium in Africa 2014年08月 口頭発表（一般）
• Effects of international land-based use of vector-control pesticides on a marine ecosystem: organochlorine analysis of fish from Maputo Bay, Mozambique  [通常講演]

  Lesa Thompson, Yoshinori Ikenaka, Yared Beyene Yohannes, Shouta M.M. Nakayama, Hazuki Mizukawa, Johannes J, van Vuren, Victor Wepener, Nico J. Smit, Volk Wynand, Mayumi Ishizuka

  6th International Toxicology Symposium in Africa 2014年08月 口頭発表（一般）
• Human and ecological health risk assessment of pesticides used for vector control: Current situation and problems of DDT use in Africa  [通常講演]

  Yoshinori Ikenaka, Yared Beyene Yohannes, Lesa Thompson, Shouta M.M. Nakayama, Hazuki Mizukawa, Johannes J, van Vuren, Victor Wepener, Nico J. Smit, Volk Wynand, Mayumi Ishizuka

  6th International Toxicology Symposium in Africa 2014年08月 口頭発表（一般）
• Contamination status of organohalogen compounds and their metabolites in the blood of pet dogs and cats  [通常講演]

  Hazuki Mizukawa, Kei Nomiyama, Miyuki Yamamoto, Yoshinori Ikenaka, Shouta M.M. Nakayama, Shinsuke Tanabe, Mayumi Ishizuka

  6th International Toxicology Symposium in Africa 2014年08月 口頭発表（一般）
• Investigation of heavy metal contamination and assessment of impact on health in Dandora dumping site, Nairobi  [通常講演]

  Hokuto Nakata, Shouta M.M. Nakayama, Hazuki Mizukawa, Yoshinori Ikenaka, Chihiro Ishii, Yared Beyene Yohannes, John Yabe, Satoru Konnai, Mayumi Ishizuka

  6th International Toxicology Symposium in Africa 2014年08月 ポスター発表
• Preliminary survey of lead poisoning in raptors from Japan  [通常講演]

  Chihiro Ishii, Shouta M.M. Nakayama, Yoshinori Ikenaka, Hazuki Mizukawa, Yared B. Yohannes, Hokuto Nakata, Keisuke Saito, Yukiko Watanabe, Shinsuke Tanabe, Kei Nomiyama, Terutake Hayashi, Yasushi Masuda, Kentaro, Q. Sakamoto, Mayumi Ishizuka

  6th International Toxicology Symposium in Africa 2014年08月 ポスター発表
• 食肉目におけるグルクロン酸抱合酵素の解析および種差  [通常講演]

  筧麻友, 池中良徳, 中山翔太, 水川葉月, 渡邉研右, 坂本健太郎, 和田昭彦, 服部薫, 田辺信介, 野見山桂, 石塚真由美

  第28回北海道薬物作用談話会 2014年07月 口頭発表（一般）
• ペット動物における有機ハロゲン化合物の汚染実態解明と水酸化代謝物の動態解析  [通常講演]

  水川葉月, 野見山桂, 中津賞, 池中良徳, 中山翔太, 田辺信介, 石塚真由美

  第28回北海道薬物作用談話会 2014年07月 口頭発表（一般）
• 鰭脚類におけるグルクロン酸抱合酵素の解析  [通常講演]

  筧麻友, 池中良徳, 中山翔太, 水川葉月, 渡邊研右, 坂本健太郎, 和田昭彦, 服部薫, 田辺信介, 野見山桂, 石塚真由美

  第41回日本毒性学会学術年会 2014年07月 口頭発表（一般）
• 鰭脚類を中心とした食肉目において異物代謝を担うグルクロン酸抱合酵素の特徴  [通常講演]

  筧麻友, 中山翔太, 水川葉月, 池中良徳, 渡邊研右, 坂本健太郎, 和田昭彦, 服部薫, 田辺信介, 野見山桂, 石塚真由美

  第41回日本毒性学会学術年会 2014年07月 ポスター発表
• ケニアの大規模ゴミ集積場・ダンドラ地域における家畜の化学物質汚染の実態と住民の健康影響評価  [通常講演]

  中田北斗, 中山翔太, 水川葉月, 池中良徳, 石井千尋, ヨハンネス ヤレド ベイヤネ, 今内覚, 石塚真由美

  第41回日本毒性学会学術年会 2014年07月 口頭発表（一般）
• 日本に生息する猛禽類の鉛汚染状況と鉛安定同位体比を指標とした汚染源の解明  [通常講演]

  石井千尋, 中山翔太, 池中良徳, 水川葉月, 中田北斗, 齊藤慶輔, 渡邊有希子, 田辺信介, 野見山桂, 林光武, 増田泰, 坂本健太郎, 石塚真由美

  第41回日本毒性学会学術年会 2014年07月 口頭発表（一般）
• Health risk assessment of atmospheric polycyclic aromatic hydrocarbons in Kumasi-Ghana  [通常講演]

  Nesta Bortey-Sam, Yoshinori Ikenaka, Shouta M.M. Nakayama, Osei Akoto, Yared Beyene Yohannes, Hazuki Mizukawa, Mayumi Ishizuka

  第23回環境化学討論会 2014年05月 口頭発表（一般）
• Lead pollution in the children in Kabwe mining area, Republic of Zambia  [通常講演]

  Shouta M.M, Nakayama, John Yabe, Yoshinori Ikenaka, Yared Beyene, Balazs Oroszlany, Nesta Bortey-Sam, Kaampwe Muzandu, Kennedy Choongo, Abel Kabalo, John Ntapisha, Aaron Mweene, Takashi Umemura, Mayumi Ishizuka

  第23回環境化学討論会 2014年05月 口頭発表（一般）
• Mohamed Tharwat El-Abbasy, Mayumi Ishizuka, Residue levels and health risk assessment of organochlorine pesticides (OCPs) in domesticated animals from Egypt  [通常講演]

  Abdallah Fikry, A. Mahmoud, Elsaid A. Eldaly, Alaa Eldin, M.A. Morshdy, Yoshinori Ikenaka, Shouta Nakayama, Hazuki Mizukawa, Yared B. Yohannes, Waleed R. El-Ghareeb

  第23回環境化学討論会 2014年05月 口頭発表（一般）
• Quantification of Neonicotinoids in human urine using liquid chromatography/tandem mass spectrometry  [通常講演]

  Jemima Tiwaa Marfo, Yoshinori Ikenaka, Shouta M, M. Nakayama, Hazuki Mizukawa, Kumiko Taira, Kazutoshi Fujioka, Yoshiko Aoyama, Osei Akoto, Mayumi Ishizuka

  第23回環境化学討論会 2014年05月 口頭発表（一般）
• 日本に生息する猛禽類における鉛汚染状況の解析、第23回環境化学討論会  [通常講演]

  石井千尋, 池中良徳, 中山翔太, 水川葉月, 齊藤慶輔, 渡邊有希子, 田辺信介, 野見山桂, 林光武, 増田泰, 坂本健太郎, 石塚真由美

  第23回環境化学討論会 2014年05月 口頭発表（一般）
• アフリカのゴミ集積場における化学物質の汚染実態と生体への健康影響の評価：ナイロビのダンドラ地域における重金属汚染の例  [通常講演]

  中田北斗, 中山翔太, 水川葉月, 池中良徳, 石井千尋, ヨハンネス ヤレド ベイヤネ, 今内覚, 石塚真由美

  第23回環境化学討論会 2014年05月 口頭発表（一般）
• ネコ科動物における有機ハロゲン化合物の代謝能解析  [通常講演]

  水川葉月, 池中良徳, 野見山桂, 田辺信介, 宇根有美, 伊藤真輝, 高江洲昇, 長野靖子, 中山翔太, 石塚真由美

  第23回環境化学討論会 2014年05月 口頭発表（一般）
• ベクターコントロールのための薬剤散布の生態系およびヒト健康に与える影響評価  [通常講演]

  池中良徳, Yared Yohannes, 中山翔太, 水川葉月, van Vuren Johannes, Wepener Victor, Smit Nico, ynand Vlok, 石塚真由美

  第23回環境化学討論会 2014年05月 口頭発表（一般）
• Pb and Cd contaminated soil may cause metal accumulation and epigenetic alteration in rat tissues  [通常講演]

  Shouta M.M. Nakayama, Yoshinori Ikenaka, Yared B. Yohannes, Balazs Oroszlany, Nesta Bortey-Sam, Kaampwe Muzandu, John Yabe, Takashi Umemura, Mayumi Ishizuka

  SOT 53rd Annual Meeting 2014年03月 口頭発表（一般）
• Lead pollution in soil, domestic animals and children from townships near a lead-zinc mine in Kabwe, Zambia  [通常講演]

  Shouta M.M, Nakayama, John Yabe, Yoshinori Ikenaka, Yared B. Yohannes, Balazs Oroszlany, Nesta Bortey-Sam, Kaampwe Muzandu, Kennedy Choongo, Abel Nketani Kabalo, John Ntapisha, Aaron Mweene, Takashi Umemura, Mayumi Ishizuka

  SOT 53rd Annual Meeting 2014年03月 口頭発表（一般）
• Pb and Cd contaminated soil may cause metal accumulation and epigenetic alteration in laboratory rat and wild black rat  [通常講演]

  Shouta M.M. Nakayama, Yoshinori Ikenaka, Yared B. Yohannes, Balazs Oroszlany, Nesta Bortey-Sam, Kaampwe Muzandu, John Yabe, Takashi Umemura, Mayumi Ishizuka

  SETAC North America 34th Annual Meeting 2013年11月 口頭発表（一般）
• Accumulation characteristics of arsenic and metals in environmental samples and wild black rat (Rattus rattus) in gold mining area, Obuasi, Ghana  [通常講演]

  Shouta M.M. Nakayama, Go Otani, Yoshinori Ikenaka, Yared B Yohannes, Osei Akoto, Joseph Apau, Elvis Baidoo, Mayumi Ishizuka

  SETAC North America 34th Annual Meeting 2013年11月 口頭発表（一般）
• Lead poisoning in children from townships around a lead-zinc mine in Kabwe, Zambia  [通常講演]

  Shouta M.M, Nakayama, John Yabe, Yoshinori Ikenaka, Kaampwe Muzandu, John Ntapisha, Aaron Mweene, Abel Kabalo, Takashi Umemura, Mayumi Ishizuka

  SETAC North America 34th Annual Meeting 2013年11月 口頭発表（一般）
• Accumulation features of organochlorine pesticides in resident birds and their prey from Ethiopian Rift Valley Region  [通常講演]

  Yared B. Yohannes, Yoshinori Ikenaka, Shouta M.M. Nakayama, Mayumi Ishizuka

  SETAC North America 34th Annual Meeting 2013年11月 口頭発表（一般）
• Species difference of warfarin sensitivity among birds can be explained by the two enzymes, cytochrome P450 and vitamin K epoxide reductase  [通常講演]

  Kensuke P, Watanabe, Yusuke K. Kawai, Minami Kawata, Shouta M.M. Nakayama, Yoshinori Ikenaka, Mayumi Ishizuka

  10th International ISSX (International Society for the Study of Xenobiotics) Meeting 2013年10月 口頭発表（一般）
• In vitroにおけるウマのジアゼパム代謝  [通常講演]

  速水秋, Wageh Sobhy Darwish, 池中良徳, 中山翔太, 石塚真由美

  第156回日本獣医学会学術集会 2013年09月 口頭発表（一般）
• Accumulation of metals and metalloid in organs of rats, sheep and goats from Dunkwa-on-Offin, Ghana  [通常講演]

  emima T. Marfo, Osei Akoto, Elvis Baidoo, Shouta M, M. Nakayama, Yoshinori Ikenaka, Mayumi Ishizuka

  5th International Toxicology Symposium in Africa 2013年09月 口頭発表（一般）
• Distribution of toxic metals in organs of free range chicken, goat and sheep near gold mines in Tarkwa, Ghana  [通常講演]

  Nesta Bortey-Sam, Osei Akoto, Yoshinori Ikenaka, Shouta M.M. Nakayama, Elvis Baidoo, Mayumi Ishizuka

  5th International Toxicology Symposium in Africa 2013年09月 口頭発表（一般）
• The characteristics and mechanism of pyrene metabolism in freshwater turtles and the suggested genetic background  [通常講演]

  Balazs Oroszlany, Yoshinori Ikenaka, Aksorn Saengtienchai, Mami Oguri, Shouta M.M. Nakayama, Mayumi Ishizuka

  5th International Toxicology Symposium in Africa 2013年09月 口頭発表（一般）
• Lead poisoning in children from townships in the vicinity of a lead-zinc mine in Kabwe, Zambia  [通常講演]

  John Yabe, Shouta M.M. Nakayama, Yoshinori Ikenaka, Yared B. Yohannes, Balazs Oroszlany, Nesta Bortey-Sam, Kaampwe Muzandu, Kennedy Choongo, Abel Nketani Kabalo, John Ntapisha, Aaron Mweene, Takashi Umemura, Mayumi Ishizuka

  5th International Toxicology Symposium in Africa 2013年09月 口頭発表（一般）
• Lead and cadmium pollution in soil and edible tissues of cattle and chickens from townships near a lead-zinc mine in Kabwe, Zambia  [通常講演]

  Shouta M.M, Nakayama, John Yabe, Yoshinori Ikenaka, Kaampwe Muzandu, Kennedy Choongo, Takashi Umemura, Mayumi Ishizuka

  5th International Toxicology Symposium in Africa 2013年09月 口頭発表（一般）
• Assessment of heavy metals into rivers of Katanga, DR Congo  [通常講演]

  John Ngoy Kalenga, Tetsuhiko Takai, Yoshinori Ikenaka, Shouta Nakayama, Mayumi Ishizuka

  5th International Toxicology Symposium in Africa 2013年09月 口頭発表（一般）
• OCPs in fish species from Lake Ziway, Ethiopia: Association with trophic level and human health risk assessment  [通常講演]

  Yared B. Yohannes, Yoshinori Ikenaka, Shouta M.M. Nakayama, Mayumi Ishizuka

  5th International Toxicology Symposium in Africa 2013年09月 口頭発表（一般）
• Characterization and interspecies diversity of xenobiotic metabolism: a study of phase-II conjugation reactions  [通常講演]

  Yoshinori Ikenaka, Aksorn Saengtienchai, Shouta M.M. Nakayama, Hazuki Mizukawa, Mayumi ISHIZUKA

  5th International Toxicology Symposium in Africa 2013年09月 口頭発表（一般）
• Lead poisoning in children from townships in the vicinity of a lead-zinc mine in Kabwe, Zambia  [通常講演]

  ohn Yabe, Shouta M.M. Nakayama, Yoshinori Ikenaka, Yared B. Yohannes, Nesta Bortey-Sam, Balazs Oroszlany, Kaampwe Muzandu, Kennedy Choongo, John Ntapisha, Aaron Mweene, Abel Kabalo, Koji Arizono, Takashi Umemura, Mayumi Ishizuka

  6th SETAC Africa Conference 2013年09月 口頭発表（一般）
• OCPs profiles in Birds and Their Prey from Ethiopian Rift Valley Region  [通常講演]

  Yared B. Yohannes, Yoshinori Ikenaka, Shouta M.M. Nakayama, Mayumi Ishizuka

  6th SETAC Africa Conference 2013年09月 口頭発表（一般）
• ガーナの金鉱山周辺（オブアシ自治区）におけるヒ素汚染と陸生哺乳類への毒性影響評価  [通常講演]

  大谷豪, 池中良徳, 中山翔太, Osei Akoto, Joseph Apau, Elvis Baidoo, 石塚真由美

  第22回環境化学討論会 2013年07月 口頭発表（一般）
• 鳥類における金属の汚染状況と蓄積特性の解析  [通常講演]

  石井千尋, 池中良徳, 中山翔太, 鈴木優也, 綿貫豊, 渡邊雄児, 福若雅章, Yared Yohannes, 川合佑典, 石塚真由美

  第22回環境化学討論会 2013年07月 口頭発表（一般）
• 野生げっ歯類におけるワルファリン抵抗性機構  [通常講演]

  池中良徳, 田中和之, 中山翔太, 春成常仁, 谷川力, 水川葉月, 石塚真由美

  第22回環境化学討論会 2013年07月 口頭発表（一般）
• Effects of Pb and Cd contaminated soil on metal accumulation and epigenetic alteration in rat  [通常講演]

  Shouta M.M. Nakayama, Yoshinori Ikenaka, Kaampwe Muzandu, John Yabe, Takashi Umemura, Mayumi Ishizuka

  第22回環境化学討論会 2013年07月 口頭発表（一般）
• OCPs in Fish and Bird Species from a DDT Spraying and Agriculture Area in Ethiopia  [通常講演]

  Yared B. Yohannes, Yoshinori Ikenaka, Shouta M.M. Nakayama, Mayumi Ishizuka

  22nd Symposium on Environmental Chemistry 2013年07月 口頭発表（一般）
• Incidence of Metals and Polycyclic Aromatic Hydrocarbons (PAHs) in Surface Soils from the Kumasi Metropolis, Ghana- GIS Based Approach  [通常講演]

  Nesta Bortey-Sam, Osei Akoto, Yoshinori Ikenaka, Elvis Baidoo, Beyene Yared, Shouta M.M. Nakayama, Mayumi Ishizuka

  22nd Symposium on Environmental Chemistry 2013年07月 口頭発表（一般）
• The study of xenobiotic metabolism phase II reactions in pigs:sulfotransferase enzymatic efficiency observed by in vitro kinetic analysis  [通常講演]

  Aksorn Saengtienchai, Yoshinori Ikenaka, Wageh Sobhy Darwish, Yusuke K. Kawai, Shouta M.M. Nakayama, Shigeo Ito, Mayumi Ishizuka

  International Congress of Toxicology 2013 2013年06月 口頭発表（一般）
• Regulatory effects of carotenoids on Aryl hydrocarbon receptor (AhR) gene battery  [通常講演]

  Wageh Sobhy Darwish, Yoshinori Ikenaka, Shouta Nakayama, Mayumi Ishizuka

  The 40th Annual Meeting of the Japanese Society of Toxicology 2013年06月 口頭発表（一般）
• Pyrene metabolism and the role of phase I and phase II enzymes in freshwater turtles,  [通常講演]

  Balazs Oroszlany, Yoshinori Ikenaka, Aksorn Saengtienchai, Mami Oguri, Shouta M.M. Nakayama, Mayumi Iishizuka

  The 40th Annual Meeting of the Japanese Society of Toxicology 2013年06月 口頭発表（一般）
• Characteristics of phase II metabolism reaction in pig: Clear sulfation and sulfotransferase activity observed in pyrene  [通常講演]

  Aksorn Saengtienchai, Yoshinori Ikenaka, Shouta M.M. Nakayama, Yusuke Kawai, Mayumi Ishizuka

  第155回 日本獣医学会学術集会 2013年03月 口頭発表（一般）
• 海鳥における金属の汚染状況と蓄積特性の解析  [通常講演]

  石井千尋, 池中良徳, 中山翔太, 鈴木優也, 綿貫豊, 渡邊雄児, 福若雅章, Yared Yohannes, 川合佑典, 石塚真由美

  第155回 日本獣医学会学術集会 2013年03月 口頭発表（一般）
• Bioaccumulation levels of organochlorine pesticides in fish species from Ethiopian Rift Valley Lake Ziway, Ethiopia  [通常講演]

  Yared B. Yohannes, Yoshinori Ikenaka, Shouta M.M. Nakayama, Aksorn Saengtienchai, Kensuke Watanabe, Mayumi Ishizuka

  SETAC Asia/Pacific Annual Meeting 2012 2012年09月 口頭発表（一般）
• Metal contaminated soil from mining area caused accumulation and biological responses in rats −from field and laboratory studies−  [通常講演]

  Shouta M.M. Nakayama, Yoshinori Ikenaka, Kaampwe Muzandu, Kennedy Choongo, John Yabe, Takashi Umemura, Mayumi Ishizuka

  SETAC Asia/Pacific Annual Meeting 2012 2012年09月 口頭発表（一般）
• In vitro diazepam metabolism in horses  [通常講演]

  Aki Hayami, Wageh Sobhy DARWISH, Yoshinori Ikenaka, Shouta M.M. Nakayama, Mayumi Ishizuka

  4th International Toxicology Symposium in Africa 2012年09月 口頭発表（一般）
• Heavy metal pollution in sea birds  [通常講演]

  Chihiro Ishii, Yoshinori Ikenaka, Shouta M.M. Nakayama, Yuya Suzuki, Yutaka Watanuki, Yuji Watanabe, Masa-aki Fukuwaka, John Yabe, Yared B. Yohannes, Yusuke K. Kawai, Mayumi Ishizuka

  4th International Toxicology Symposium in Africa 2012年09月 口頭発表（一般）
• Metabolism of pyrene, a polycyclic aromatic hydrocarbon in freshwater turtles  [通常講演]

  Balazs Oroszlany, Yoshinori Ikenaka, Aksorn Saengtiengchan, Mami Oguri, Shouta M.M. Nakayama, Mayumi Ishizuka

  4th International Toxicology Symposium in Africa 2012年09月 口頭発表（一般）
• Metal contaminated soil from mining area caused metal accumulation and biological responses in rats −from field and laboratory studies−  [通常講演]

  Shouta M.M. Nakayama, Yoshinori Ikenaka, Kaampwe Muzandu, Kennedy Choongo, John Yabe, Takashi Umemura, Mayumi Ishizuka

  4th International Toxicology Symposium in Africa 2012年09月 口頭発表（一般）
• Levels and Bioaccumulation of Organochlorine Pesticides in Fish Species from Lake Ziway, ETHIOPIA  [通常講演]

  Yared B. Yohannes, Yoshinori IKENAKA, Kensuke WATANABE, Aksorn SAENGTIENCHAI, Shouta NAKAYAMA, Mayumi ISHIZUKA

  21th symposium on Environmental Chemistry 2012年07月 口頭発表（一般）
• GIS based source estimation of Cu pollution in Lake Itezhi-tezhi and Cu accumulation profile in Oreochromis sp. from the field and laboratory studies  [通常講演]

  Shouta M.M. Nakayama, Yoshinori Ikenaka, Kaampwe Muzandu, Kennedy Choongo, John Yabe, Taro Muroya, Shigeho Ijiri, Takashi Umemura, Mayumi Ishizuka

  SETAC North America 32nd Annual Meeting 2011年11月 口頭発表（一般）
• アカハライモリとアフリカツメガエルにおける異物代謝酵素の比較  [通常講演]

  上田春樹, 中山翔太, 川合佑典, 田中-上野寛子, 池中良徳, 石塚真由美

  日本爬虫両棲類学会 第50回大会 2011年10月 口頭発表（一般）
• ラットにおける薬物代謝酵素シトクロムP450の系統差について  [通常講演]

  西山義広, 池中良徳, 大野円実, 渡邉研右, 川合佑典, 中山翔太, 田中和之, 石塚真由美

  第152回日本獣医学会学術集会 2011年09月 口頭発表（一般）
• ラットの消化管における異物代謝酵素の比較  [通常講演]

  糸谷悠美, 池中良徳, 大野円実, 中山翔太, ワギ ソベイ, 石塚真由美

  第152回日本獣医学会学術集会 2011年09月 口頭発表（一般）
• GIS-based source estimation of Cu pollution in Lake Itezhi-tezhi and metal accumulation profiles in Oreochromis sp. and other fish species from both and laboratory studies  [通常講演]

  Shouta M.M. Nakayama, Yoshinori Ikenaka, Kaampwe Muzandu, Kennedy Choongo, John Yabe, Taro Muroya, Shigeho Ijiri, Takashi Umemura, Mayumi Ishizuka

  3rd International Toxicology Symposium in Africa 2011年09月 口頭発表（一般）
• Effects of current malaria control in lake environment; The levels of Organochlorine pesticide and toxic metals in fish species from Lake Awassa, Ethiopia  [通常講演]

  Yoshinori IKENAKA, Yared Beyene, Kensuke WATANABE, Aksorn Saengtienchai, Shouta NAKAYAMA, Mayumi ISHIZUKA

  3rd International Toxicology Symposium in Africa 2011年09月 口頭発表（一般）
• ガーナの金鉱山周辺（オブアシ自治区）における金属汚染と野生ラットにおける毒性影響評価  [通常講演]

  大谷豪, 池中良徳, 中山翔太, Osei Akoto, Joseph APAU, Elvis BAIDOO, 石塚真由美

  第20回環境化学討論会 2011年07月 口頭発表（一般）
• Effects of current malaria control in lake environment; The levels of Organochlorine pesticide and toxic metals in fish species from Lake Awassa, ETHIOPIA  [通常講演]

  YARED Beyene, Yoshinori IKENAKA, Kensuke WATANABE, Aksorn SAENGTIENCHAI, Shouta NAKAYAMA, Mayumi ISHIZUKA

  第20回環境化学討論会 2011年07月 口頭発表（一般）
• Metal and metalloid levels and bio-accumulation characteristics in soil, sediment, land plants and hippopotami (Hippopotamus amphibius L) from the South Luangwa National Park, Zambia  [通常講演]

  Shouta M.M. Nakayama, Yoshinori Ikenaka, Kaampwe Muzandu, Kennedy Choongo, Ethel M’kandawire, Jun Yasuda, Mayumi Ishizuka

  第20回環境化学討論会 2011年07月 口頭発表（一般）
• Metal concentration and stable isotope ratio analysis (d13C and d15N) in water, sediment and fish from Lake Itezhi-tezhi, Zambia  [通常講演]

  Shouta M.M. Nakayama, Yoshinori Ikenaka, Kaampwe Muzandu, Kennedy Choongo, John Yabe, Taro Muroya, Takashi Umemura, Mayumi Ishizuka

  第20回環境化学討論会 2011年07月 口頭発表（一般）
• Concentration and bioaccumulation of 10 metals in soil, river sediment, plant and hippopotamus (Hippopotamus amphibius L) in the South Luangwa National Park, Zambia  [通常講演]

  Shouta M.M. Nakayama, Yoshinori Ikenaka, Kaampwe Muzandu, Kennedy Choongo, Jun Yasuda, Mayumi Ishizuka

  3rd CSTS and 5th SETAC- Africa Joint Toxicology Conference 2011年06月 口頭発表（一般）
• Metal concentration and stable isotope ratio analysis (d13C and d15N) in water, sediment and fish from Lake Itezhi-tezhi, Zambia  [通常講演]

  Shouta M.M. Nakayama, Yoshinori Ikenaka, Kaampwe Muzandu, Kennedy Choongo, Jun Yasuda, Mayumi Ishizuka

  3rd CSTS and 5th SETAC- Africa Joint Toxicology Conference 2011年06月 口頭発表（一般）

その他活動・業績

• 哺乳類・鳥類における異物代謝に関わるグルクロン酸抱合酵素(UGT)遺伝子の進化と植物の関わり

  川合佑典, 池中良徳, 池中良徳, 生城真一, 西川美宇, 一色乃亜, 武田一貴, 中山翔太, 中山翔太, 久保田彰, 石塚真由美 日本進化学会大会プログラム・講演要旨集(Web) 25th 2023年
• アオウミガメの汚染物質の影響評価を可能にするリソース開発

  片山雅史, 福田智一, 大沼学, 武田一貴, 近藤理美, 中山翔太, 中山翔太 日本地球惑星科学連合大会予稿集(Web) 2022 2022年
• メタボロミクスおよび甲状腺ホルモン分析による有機ハロゲン汚染物質への曝露によって引き起こされたペット猫(Felis silvestris catus)の健康影響評価

  野見山 桂, 山本 恭央, 江口 哲史, 西川 博之, 水川 葉月, 横山 望, 市居 修, 滝口 満喜, 中山 翔太, 池中 良徳, 石塚 真由美, 国末 達也 環境ホルモン学会研究発表会要旨集 23回 55 -55 2021年09月
• Comprehensive analysis of steroid profile in dogs with Cushing' syndrome and hepatocellular carcinoma(和訳中)

  Oo Thandar, 佐々木 東, 池中 良徳, 永田 矩之, 一瀬 貴大, Bin Teoh Yong, 川元 誠, 小島 一輝, 菅原 芽伊, 中山 翔太, 石塚 真由美, 中村 健介, 滝口 満喜 日本獣医学会学術集会講演要旨集 164回 [HSO -18] 2021年09月
• 液体クロマトグラフィー質量分析法によるアフリカゾウの血中ステロイドホルモン濃度測定法の確立および無排卵雌における排卵誘起の試み

  篠原明, 篠原明, 鳥居佳子, 入江陽一, 牛尾佳名子, 曽地千尋, 宗内一平, 楠田哲士, 東達也, 一瀬貴大, 中山翔太, 石塚真由美, 池中良徳, 片桐成二, 柳川洋二郎 日本獣医学会学術集会講演要旨集 164th (CD-ROM) 2021年
• 鉛中毒マウスの短期作業記憶低下および血中ステロイドの分析

  村上昂暉, 中山翔太, 一瀬貴大, 中田北斗, YARED B. Yohannes, YARED B. Yohannes, ANDREW Kataba, ANDREW Kataba, 平井杏梨, 池中良徳, 石塚真由美 日本獣医学会学術集会講演要旨集 164th (CD-ROM) 2021年
• 希少鳥類の鉛毒性に関する基盤技術開発

  石塚真由美, 池中良徳, 石井千尋, 中田北斗, 中山翔太 日本獣医学会学術集会講演要旨集 164th (CD-ROM) 2021年
• 近年の野生鳥類における鉛中毒

  小笠原浩平, 渡辺有希子, 安達光, 河野晴子, 中山翔太, 石井千尋, 池中良徳, 大沼学, 石塚真由美, 齊藤慶輔 環境ホルモン学会研究発表会プログラム・要旨集 23rd (Web) 2021年
• カエルに対するネオニコチノイド系殺虫剤クロチアニジンの毒性評価

  西部詞哉, 池中良徳, 一瀬貴大, 新屋惣, 中山翔太, 石塚真由美 環境ホルモン学会研究発表会プログラム・要旨集 23rd (Web) 2021年
• ゲノムデータベースを利用した脊椎動物がもつグルクロン酸抱合遺伝子の進化解析

  川合佑典, 池中良徳, 中山翔太, 久保田彰, 石塚真由美 環境ホルモン学会研究発表会プログラム・要旨集 23rd (Web) 2021年
• xenobiotics代謝と解毒の動物種差-introduction-

  石塚真由美, 中山翔太, 池中良徳 Journal of Toxicological Sciences 46 (Supplement) 2021年
• 殺虫剤が神経系に与える影響評価~モノアミン系神経伝達物質の高感度分析法の確立と応用~

  池中良徳, 平井杏里, 野見山桂, 新間秀一, 一瀬貴大, 中山翔太, 石塚真由美 JSBMS Letters 46 (Supplement) 2021年
• LC-MS/MSを用いたステロイドホルモンの一斉分析法による,副腎皮質機能亢進症(クッシング症候群)の病態解明について

  一瀬貴大, 安田淑一, 佐々木東, 滝口満喜, 中山翔太, 石塚真由美, 池中良徳 JSBMS Letters 46 (Supplement) 2021年
• ニコチン性アセチルコリン受容体アゴニストによるマウスの脳機能攪乱~二光子顕微鏡を用いた検出法の開発~

  平井杏梨, 杉尾翔太, NIMAKO Collins, 中山翔太, 加藤恵介, 高橋圭介, 有薗幸司, 平野哲史, 星信彦, 石塚真由美, 和氣弘明, 池中良徳 環境化学討論会要旨集(CD-ROM) 29th 2021年
• C57BL/6Jマウスにおける鉛中毒と肥満に関連するパラメータに対するスピルリナ(Arthrospira platensis)補給の改善効果の評価【JST・京大機械翻訳】

  Nakata Hokuto, Nakayama Shouta M.M., Kataba Andrew, Kataba Andrew, Yohannes Yared Beyene, Yohannes Yared Beyene, Ikenaka Yoshinori, Ikenaka Yoshinori, Ishizuka Mayumi Journal of Functional Foods 77 2021年
• バレンプレートの炭素と窒素安定同位体分析を用いた妊娠南極ミンククジラ(Balaenoptera bonaerensis)の摂食記録の推定【JST・京大機械翻訳】

  Uchida Mayuka, Suzuki Ippei, Suzuki Ippei, Ito Keizo, Ito Keizo, Ishizuka Mayumi, Ikenaka Yoshinori, Ikenaka Yoshinori, Nakayama Shouta M. M., Tamura Tsutomu, Konishi Kenji, Bando Takeharu, Mitani Yoko Polar Biology 44 (3) 2021年
• ニコチン性アセチルコリン受容体アゴニストによるシグナル毒性と2光子顕微鏡を用いた検出手法の開発

  平井 杏梨, 杉尾 翔太, 池中 良徳, Collins Nimako, 中山 翔太, 星 信彦, 和氣 弘明, 石塚 真由美 The Journal of Toxicological Sciences 45 (Suppl.) S86 -S86 2020年06月
• エジプシャンルーセットオオコウモリ(Rousettus aegyptiacus)における抗血液凝固系殺鼠剤の薬物動態学/薬力学的解析

  武田 一貴, 真砂 皓大, 中山 翔太, 川合 佑典, 池中 良徳, 石塚 真由美 The Journal of Toxicological Sciences 45 (Suppl.) S181 -S182 2020年06月
• ヒゲ板中安定同位体比から推定するクロミンククジラ成熟雄の回遊生態

  石川啓史, 石塚真由美, 池中良徳, 中山翔太, 坂東武治, 田村力, 小西健志, 大槻真友子, 三谷曜子 日本水産学会大会講演要旨集 2020 2020年
• 添加剤含有プラスチック投与による海鳥への毒性影響の評価

  青木真奈実, 田中厚資, 池中良徳, 中山翔太, 綿貫豊, 高田秀重, 石塚真由美 日本獣医学会学術集会講演要旨集 163rd 2020年
• 行動毒性試験および二光子イメージングによるアセタミプリドの神経毒性評価

  平井杏梨, 杉尾翔太, 池中良徳, COLLINS Nimako, 中山翔太, 星信彦, 和氣弘明, 石塚真由美 日本獣医学会学術集会講演要旨集 163rd 2020年
• ペット動物から見る室内化学物質汚染の実態解明とリスク評価

  水川 葉月, 野見山 桂, 池中 良徳, 中山 翔太, 石塚 真由美, 高橋 真 環境ホルモン学会研究発表会要旨集 22回 45 -45 2019年12月
• 鉛散弾の経口投与によるバルバリーガモの鉛の血中濃度の経時変化および体内分布の解析

  佐藤裕, 石井千尋, 中山翔太, 一瀬貴大, 齊藤慶輔, 渡邊有希子, 小笠原浩平, 鳥本亮太, 小林篤史, 木村享史, 池中良徳, 石塚真由美 日本獣医学会学術集会講演要旨集 162nd 504 2019年08月20日 [査読無し][通常論文]
  
• 鳥類におけるUGT1E遺伝子の進化と食性の関わり

  川合佑典, 新屋惣, 中山翔太, 池中良徳, 石塚真由美, 久保田彰 日本進化学会大会プログラム・講演要旨集(Web) 21st 116 (WEB ONLY) 2019年08月07日 [査読無し][通常論文]
  
• LC-MS/MSを用いたイヌ尿中メタネフリンおよびノルメタネフリン測定

  井上 裕美子, 佐々木 東, 池中 良徳, 一瀬 貴大, 笹岡 一慶, 大菅 辰幸, 中山 翔太, 森下 啓太郎, 大田 寛, 石塚 真由美, 滝口 満喜 日本獣医学会学術集会講演要旨集 162回 470 -470 2019年08月 [査読無し][通常論文]
  
• LC-MS/MS法を用いたイヌ血清中ステロイドホルモンの分析法の確立と内分泌疾患モデルを用いた実測

  白尾 大樹, 池中 良徳, 一瀬 貴大, 中山 翔太, 佐々木 東, 永田 矩之, 水川 葉月, 滝口 満喜, 石塚 真由美 日本獣医学会学術集会講演要旨集 162回 470 -470 2019年08月 [査読無し][通常論文]
  
• 体内動態および行動毒性試験から見た動物用医薬品フィプロニルの影響評価

  鈴木 智裕, 池中 良徳, 中山 翔太, 水川 葉月, 一瀬 貴大, 佐々木 東, 笹岡 一慶, 石塚 真由美 日本獣医学会学術集会講演要旨集 162回 501 -501 2019年08月 [査読無し][通常論文]
  
• 野生ラットを用いたDDT汚染状況の評価,毒性機序の解明

  本平航大, 池中良徳, 池中良徳, BEYENE Yared, 中山翔太, WEPENER Victor, SMIT Nico, VAN VUREN Johan, 江口哲史, SOUSA Ana Catarina, 石塚真由美 環境化学討論会要旨集(CD-ROM) 28th ROMBUNNO.2A‐06 2019年06月11日 [査読無し][通常論文]
  
• ザンビア共和国カブエ地域における資源採掘に起因した鉛汚染の実態解明と対策の検討:環境化学のその先へ

  中田北斗, 中山翔太, YABE John, MUZANDU Kaampwe, 豊巻治也, BEYENE Yared, KATABA Andrew, KATABA Andrew, ZYAMBO Golden, CHOONGO Kennedy, 池中良徳, 石塚真由美 環境化学討論会要旨集(CD-ROM) 28th ROMBUNNO.1C‐18 2019年06月11日 [査読無し][通常論文]
  
• PCBs曝露によるネコ肝トランスクリプトームへの影響

  水川葉月, NGYUEN Hoa Thanh, 岩田久人, 野見山桂, 池中良徳, 中山翔太, 横山望, 市居修, 滝口満喜, KHIDKHAN Kraisiri, 田辺信介, 石塚真由美 環境化学討論会要旨集(CD-ROM) 28th ROMBUNNO.1C‐08 2019年06月11日 [査読無し][通常論文]
  
• 摂食プラスチックから海鳥への化学物質の移行の検証

  田中厚資, 綿貫豊, 高田秀重, 石塚真由美, 山下麗, 水川薫子, 水川葉月, 池中良徳, 中山翔太 環境化学討論会要旨集(CD-ROM) 28th ROMBUNNO.P‐031 2019年06月11日 [査読無し][通常論文]
  
• LC‐MS/MSを用いたイヌ血清中ステロイドホルモンの分析法の確立と副腎疾患モデルを用いた実測

  白尾大樹, 池中良徳, 一瀬貴大, 中山翔太, 佐々木東, 永田矩之, 水川葉月, 滝口満善, 石塚真由美 環境化学討論会要旨集(CD-ROM) 28th ROMBUNNO.1A‐10 2019年06月11日 [査読無し][通常論文]
  
• ネオニコチノイドの母子間移行の実態と移行メカニズムの解明

  池中良徳, 池中良徳, 一瀬貴大, NIMAKO Collins, 市川剛, 野見山桂, 長谷川浩, 中山翔太, 星信彦, 平久美子, 石塚真由美 環境化学討論会要旨集(CD-ROM) 28th ROMBUNNO.2B‐05 2019年06月11日 [査読無し][通常論文]
  
• デカブロモジフェニルエーテル(BDE209)の長期曝露がイエネコへ及ぼす影響

  田中啓介, 野見山桂, 水川葉月, 水川葉月, 高口倖暉, 田上瑠美, 横山望, 市居修, 滝口満喜, 笹岡一慶, 中山翔太, 池中良徳, 石塚真由美, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 28th ROMBUNNO.1C‐09 2019年06月11日 [査読無し][通常論文]
  
• 血漿中のステロイドホルモンの一斉分析法の開発とウマ性ホルモンの季節変動の解明

  一瀬貴大, 池中良徳, 池中良徳, 三津橋嵩史, 中山翔太, SAENGTIENCHAI Aksorn, 野見山桂, 田上瑠美, 石塚真由美 環境化学討論会要旨集(CD-ROM) 28th ROMBUNNO.P‐106 2019年06月11日 [査読無し][通常論文]
  
• ネオニコチノイド系殺虫剤と農薬の現状と今後の展望〜毒性学・農学・行政の視点から〜 ネオニコチノイド系殺虫剤の曝露実態の解明と毒性評価

  池中 良徳, 一瀬 貴大, Nimako Collins, 中山 翔太, 平野 哲史, 市川 剛, 加藤 恵介, 高橋 圭介, 長谷川 浩, 平 久美子, 有薗 幸司, 星 信彦, 藤岡 一俊, 石塚 真由美 The Journal of Toxicological Sciences 44 (Suppl.) S53 -S53 2019年06月 [査読無し][通常論文]
  
• Assessing the population-wide exposure to lead pollution in Kabwe, Zambia : blood lead level estimation based on survey data

  Hiwatari Masato, Yamada Daichi, Hangoma Peter, Narita Daiju, Mphuka Chrispin, Chitah Bona, Yabe John, Nakayama Shouta MM, Nakata Hokuto, Choongo Kennedy, Ishizuka Mayumi Discussion Paper, Series A (338) 1 -28 2019年05月
• ヒゲ板中安定同位体比変動から推定するクロミンククジラ雌の生活史履歴

  打田茉由果, 石塚真由美, 池中良徳, 水川葉月, 中山翔太, 坂東武治, 田村力, 小西健志, 鈴木一平, 三谷曜子 日本水産学会大会講演要旨集 2019 162 2019年03月26日 [査読無し][通常論文]
  
• 鉛汚染は末梢血中の免疫系細胞を変動させるのか?

  牛根奈々, 中山翔太, 石塚真由美, 羽山伸一 日本野生動物医学会大会・講演要旨集 25th 2019年
• PCR法によるオオワシ(Haliaeetus pelagicus)の孵化前雌雄判定

  中山翔太, 平野なぎ沙, 境秀文, 五島渉, 伊藤真輝, 池中良徳, 石塚真由美 日本野生動物医学会大会・講演要旨集 25th 2019年
• オガサワラオオコウモリ(Pteropus pselaphon)のリスク評価のためのエジプトフルーツバット(Rousettus aegyptiacus)での第一世代抗凝血性殺鼠剤ワルファリンのin vivo薬物動態/薬力学解析

  NAKAYAMA Shouta M.M., MANAGO Kosuke, TAKEDA Kazuki, MORITA Ayuko, IKENAKA Yoshinori, ISHIZUKA Mayumi 環境化学討論会要旨集(CD-ROM) 28th 2019年
• DDTによる異物代謝酵素の遺伝子発現撹乱と健康影響評価

  本平航大, 池中良徳, 池中良徳, BEYENE Yared, 中山翔太, 江口哲史, 武田一貴, WEPENER Victor, SMIT Nico, VAN VUREN Johan, 石塚真由美 日本分子生物学会年会プログラム・要旨集(Web) 42nd 2019年
• 「基質結合部位からも活性残基からも離れたアミノ酸変異はどのように殺鼠剤抵抗性に寄与するのか?」ドッキングシミュレーション・分子動力学シミュレーションによるビタミンKエポキシド還元酵素の解析

  武田一貴, 池中良徳, 池中良徳, FOURCHES Denis, 田中和之, 中山翔太, 谷川力, TRIKI Dhoha, LI Xinhao, 石塚真由美 日本分子生物学会年会プログラム・要旨集(Web) 42nd 2019年
• 東京都小笠原諸島における殺鼠剤散布のアオウミガメへのリスク評価

  山村快哉, 武田一貴, 中山翔太, 川合佑典, 森田鮎子, 池中良徳, 小松謙之, 北山知代, 近藤理美, 石塚真由美 日本野生動物医学会大会・講演要旨集 25th 2019年
• グルクロン酸化と硫酸化プロファイリングを通じた哺乳類における生体異物代謝のキャラクタリゼーションと差別化

  SAENGTIENCHAI Aksorn, IKENAKA Yoshinori, NAKAYAMA Shouta M.M., ISHIZUKA Mayumi 環境化学討論会要旨集(CD-ROM) 28th 2019年
• 齧歯類モデルにおけるネオニコチノイド殺虫剤と高脂肪食2型糖尿病発症促進シグナルの相互作用

  NIMAKO Collins, IKENAKA Yoshinori, IKENAKA Yoshinori, OKAMATSU-OGURA Yuko, KOBAYASHI Atsushi, NAKAYAMA Shouta M.M., ISHIZUKA Mayumi 環境化学討論会要旨集(CD-ROM) 28th 2019年
• ネオニコチノイド系殺虫剤の曝露実態の解明と毒性評価

  池中 良徳, 平 久美子, 有薗 幸司, 星 信彦, 藤岡 一俊, 石塚 真由美, 一瀬 貴大, Collins NIMAKO, 中山 翔太, 平野 哲史, 市川 剛, 加藤 恵介, 高橋 圭介, 長谷川 浩 日本毒性学会学術年会 46 (0) S7 -2 2019年 [査読無し][通常論文]
   

  ネオニコチノイド（NNs）は、現在世界で最も使用されている殺虫剤の一つである。特に日本では、果物や野菜における残留基準値が諸外国と比べ高く設定され、かつ複数種が使用されるため、全体的にNNsの摂取量が多いと考えられる。

  そこで本研究では、日本人におけるNNs曝露実態を明らかにする事を目的に、新生児、幼児を含む延べ数百人から尿を採取し、尿中に含まれる7種のNNs（アセタミプリド、イミダクロプリド、チアメトキサム、チアクロプリド、ニテンピラム、クロチアニジン、ジノテフラン）及び代謝物（N-デスメチルアセタミプリド）をLC/MS/MSで定量した。更に、得られた尿中データより、推定摂取量を算出し、一日摂取許容量（ADI）と比較した。

  分析の結果、日本人の尿から何らかのNNsが検出され、特に、N-デスメチルアセタミプリド（90％）、クロチアニジン（50％）、ジノテフラン（50％）の検出頻度が高かった。一方、尿中濃度から推定した各NNs摂取量は、10～50 µg/dayであり、ADIに比べアセタミプリドで最大1％程度、他のNNsは1％未満であった。更に本研究では、生後48時間以内の新生児の尿も分析した。その尿中濃度は‹LOD～0.7 ng/mLと極めて低かったが、分析した57サンプルのうち14サンプルから検出された。

  本研究の結果、多くの日本人は胎児を含めNNsの曝露を受けていることが明らかにされた。NNsの慢性低濃度曝露の健康影響については、胎児移行のメカニズムや神経発達を含む毒性に不明な点が多いが、最近の報告においてNNsは現在のNOAELの1/10程度の曝露でも実験動物に対し不安などの情動認知行動に影響を与える事が示されている。

  NNsの毒性について、再度リスク評価を実施した上で、継続的なモニタリングを行う必要がある。

• ペットボトル緑茶飲料中のネオニコチノイド系農薬および代謝物の分析と安全性評価

  高本 亜希子, 石橋 弘志, 石塚 真由美, 有薗 幸司, 池中 良徳, 杉本 真夕, 岩野 まな美, 福島 聡, 一瀬 貴大, 中山 翔太, 高橋 圭介, 加藤 恵介 日本食品化学学会誌 26 (1) 17 -27 2019年 [査読無し][通常論文]
   

  In this study, we determined the concentration of seven neonicotinoid insecticides and 13 of their metabolites in 46 bottled greenteabeverages, and estimated the daily intake of neonicotinoids in adults and children from these drinks. Liquid chromatographycoupled with electrospray ionization tandem mass spectrometry (LC–ESI/MS/MS) analysis revealed that six neonicotinoidsand two metabolites were detected in bottled green-tea beverages, and the 50th percentile concentration indicated dinotefuran > thiacloprid > clothianidin > imidacloprid > thiamethoxam > acetamiprid > N-desmethyl-acetamiprid > thiacloprid-amide. Theconcentration and composition profile of neonicotinoids in bottled green-tea beverages were different between brands; however,no significant differences were observed among manufacturing sites. The concentration of acetamiprid in bottled green-teabeverages was significantly correlated with that of N-desmethyl-acetamiprid. A significant relationship between concentrations ofthiamethoxam and clothianidin in bottled green-tea beverages was also observed, suggesting those neonicotinoids are metabolizedduring the tea leaves cultivation period. The daily intake for neonicotinoids in both adults and children from consumption ofbottled green-tea beverages was < 2.1% when compared with the acceptable daily intake (ADI) of neonicotinoids.
• 海鳥の越冬期の行動が繁殖地への汚染物質輸送に与える影響

  庄子晶子, ELLIOTT K, ARIS‐BROSOU S, 水川葉月, 中山翔太, 池中良徳, 石塚真由美, 桑江朝比呂, 渡辺謙太, 綿貫豊 日本鳥学会大会講演要旨集 2018 97 2018年09月14日 [査読無し][通常論文]
  
• XAFSを用いたザンビア鉛汚染地域の生物及び環境試料における鉛の化学形態の解明

  豊巻治也, 中山翔太, 中田北斗, 藤森崇, 塩田憲司, Yabe John, Muzandu Kaampwe, Beyene Yared, 池中良徳, 水川葉月, 石塚真由美 第21回XAFS討論会 2018年09月 [査読無し][通常論文]
  
• グルクロン酸転移酵素UGT1A6と哺乳類の食性の関係

  佐野花澄, 池中良徳, 近藤誉充, 川合佑典, 中山翔太, 水川葉月, 石塚真由美 日本獣医学会学術集会講演要旨集 161st 469 2018年08月21日 [査読無し][通常論文]
  
• オジロワシを中心とした鳥類の食性による腸内細菌叢変動と影響の解析

  山田尚輝, 中山翔太, 水川葉月, 小笠原浩平, 渡邊有希子, 齊藤慶輔, 伊藤真輝, 大澤夏生, 竹中康進, 小松謙之, 千葉茜, 内田義崇, 池中良徳, 石塚真由美 日本獣医学会学術集会講演要旨集 161st 469 2018年08月21日 [査読無し][通常論文]
  
• 誘導体化液体クロマトグラフィー質量分析法(LC/MS法)によるステロイドホルモン多成分一斉分析メソッドの開発及びその応用

  三津橋嵩史, 池中良徳, 池中良徳, 中山翔太, 水川葉月, 一瀬貴大, SAENGTIENCHAI Aksorn, 河合正人, 南保泰雄, 石塚真由美 日本獣医学会学術集会講演要旨集 161st 467 2018年08月21日 [査読無し][通常論文]
  
• スーパーラットは何が「スーパー」なのか？ ～東京の殺鼠剤抵抗性クマネズミにおける抵抗性獲得機序の探索～

  武田 一貴, 池中 良徳, 田中 和之, 中山 翔太, 谷川 力, 水川 葉月, 石塚 真由美 日本毒性学会学術年会 45 (0) P -71 2018年08月10日 [査読無し][通常論文]
   

  <p> 野生げっ歯類はレプトスピラやハンタウイルス感染症、ペストなど種々の人獣共通感染症を媒介するため殺鼠剤による駆除は不可欠である。しかしワルファリン(Wf)など殺鼠剤に対し抵抗性を有する個体群が殺鼠剤使用頻度の高い世界各地の都市に出現している。現在抵抗性ラットに有効な防除策は乏しく、抵抗性獲得機序の解明と新規防除策の提案は急務である。</p><p> これまでWf抵抗性の原因はWfの標的分子ビタミンKエポキシド還元酵素の遺伝子変異だと考えられてきたが、発表者が東京の殺鼠剤抵抗性ラットでWf肝灌流試験を実施した所、肝臓でのWf代謝が亢進していた。このため、抵抗性にWfの代謝・排泄も寄与することが示唆された。また、肝臓から薬物代謝酵素シトクロムP450(CYPｓ)を含む酵素画分を調製しWf代謝試験を実施すると、ミクロソームへNADPHを添加した所CYPsの酵素活性に大きな差は認められなかったが、S9画分へNADP＋を添加するとCYPsによる代謝活性が抵抗性群で大きく上昇した。このため、肝灌流で確認された高代謝能はCYPs自体の変化ではなく、その活性に必要なNADPH産生能に起因するということが示唆された。また、実際に抵抗性ラットS9画分ではNADPHの産生が亢進していた。</p><p> このため、抵抗性ラットで確認された高NADPH産生能の責任分子を特定するため、肝臓でNADPH産生を主に担うペントースリン酸経路のNADPH産生酵素、グルコース6リン酸脱水素酵素(G6PD)について、シークエンス解析とウェスタンブロットによる発現量の定量を行った。しかしG6PD発現量自体には有意な差は認められず、アミノ酸配列においても変化は認められなかった。</p>
• ザンビア共和国カブウェ鉱床地域における鉛汚染問題：10年間の研究結果と今後の課題

  中山 翔太, ジアンボ ゴルデン, 栗谷 豪, 中川 光弘, 水川 葉月, 石塚 真由美, ヤベ ジョン, 池中 良徳, ムザンド カアンプウェ, チョーンゴ ケネディ, 中田 北斗, 豊巻 治也, ベイエネ ヤレド, カタバ アンドリュー 日本毒性学会学術年会 45 (0) P -35 2018年08月10日 [査読無し][通常論文]
   

  <p>発表者らは、2008年よりアフリカのザンビア共和国カブウェ市における鉛汚染問題に関わる研究を進めてきた。当該の鉛・亜鉛鉱床地域では、1900年頃から鉱床活動が行われているが、低効率の精錬技術による多くの不純物を含む鉱さいの排出および不適切な廃棄により、地質中の鉛やカドミウムが環境に拡散している。我々の先行研究により、家畜（ニワトリ、ヤギ、ウシ）およびイヌ、野生ラットなどの動物における血中・臓器中の高濃度の鉛蓄積を確認した。さらに、鉱床周辺に住む子供300名の血中鉛濃度は、対象のほぼ全員が研究当時の基準値である5 µg/dLを超過する深刻な状況であることを解明した。この研究結果を受けて、特に子供における治療や地域の環境汚染レベルの低減を目的としたプロジェクト（<u>KA</u>bwe <u>M</u>ine <u>P</u>ollution <u>A</u>melioration <u>I</u>nitiative ~KAMPAI Project~）を2016年より実施している。本発表では、より広範囲のエリアにおける汚染状況の解明や、鉛の暴露経路解明を目的としたプロジェクトの一部結果を発表する。</p><p>ザンビア大学、ザンビア国保健省および所属機関における研究倫理許可を取得し、鉱床付近およびそれ以外のエリアも対象とした約500世帯（父、母、子供）の合計1250名における血液・血漿・尿および子供の糞便試料を採取した。血中鉛濃度は、オンサイトで測定可能なLeadCareⅡを用いて、現地クリニックにおいて測定し、鉛汚染の広がっている範囲の概要を掴むことができた。予想に反して、鉱床から離れた地域でも高濃度の血中鉛が検出される対象者の存在も明らかになった。今後は、血液や糞便における金属濃度および鉛安定同位体比解析により鉛の人への暴露経路を解明し、環境改善手法を検討する。さらに、100年間以上にも及ぶ長期慢性暴露により、動物や人におけるゲノム・エピゲノム修飾、腸内細菌叢コミュニティ変化などの可能性を予想している。近年では、鉛の毒性発現には閾値を設定できないとされているが、長期慢性暴露に伴う毒性発現メカニズムを解明し、効果的な予防法・治療法開発に貢献したい。</p>
• 食肉目動物での第II相抱合酵素の遺伝的性状および酵素学的性状の解明

  近藤 誉充, 池中 良徳, 中山 翔太, 水川 葉月, 三谷 曜子, 野見山 桂, 田辺 信介, 石塚 真由美 日本毒性学会学術年会 45 (0) P -60 2018年08月10日 [査読無し][通常論文]
   

  <p>アザラシやネコ科を含む食肉目動物は生態系高次栄養段階に位置し、食物連鎖を介した生物濃縮により残留性の高い有機化合物が高濃度で生体内に蓄積している。化学物質代謝酵素はこれら化学物質の解毒を担う酵素である。その中でも特に第II相抱合酵素はCytochrome P450等の代謝を受けた化学物質をさらに代謝する酵素であり、発がん性物質を含む多くの化学物質がP450の代謝を受けた後に代謝的活性化を示すため、第II相酵素は特に解毒に重要な酵素である。しかし多くの食肉目動物で第II相抱合酵素の情報は皆無であり、特に基本的情報である遺伝的性状や酵素活性の種差の情報が欠如している。そこで本研究は主要な第II相抱合酵素であるグルクロン酸転移酵素（UGT）および硫酸転移酵素（SULT）の遺伝子性状およびin vitro酵素活性の解明を目的とした。遺伝的性状解析では遺伝子データベースやシークエンス解析による遺伝子情報から系統解析、および遺伝子コード領域の種差を解明した。In vitro活性解析ではネコ、イヌ、ラット、および鰭脚類（カスピカイアザラシ、ゼニガタアザラシ、トド、キタオットセイ）の肝ミクロソームおよびサイトゾルを用いて種々の分子種特異的な基質（Lorazepam：UGT2B分子種, Estradiol：SULT1E1等）に対する酵素活性を測定した。UGTに関して、系統解析の結果から食肉目で特に重要と推定される2B31分子種の存在が明らかとなった。また、食肉目の中でもイヌでは3つのUGT2B31を持つのに対して、ネコ科動物では2B分子種が存在せず、鰭脚類でも1つの分子種しか持たないことが明らかとなった。さらにin vitro活性もイヌと比較してネコ及びアザラシ科で非常に低い活性が確認された。SULTに関しては、鰭脚類でエストロゲン代謝に重要なSULT1E1分子種が遺伝的に欠損しており、in vitro活性も低いことが解明された。これらの結果から食肉目動物の中でもとくに鰭脚類やネコ科動物では第II相抱合酵素による解毒能が弱く、種々の化学物質に対して感受性が強い可能性が示唆された。</p>
• 殺鼠剤に弱い野生動物種を探る:標的分子ビタミンKエポキシド還元酵素(VKOR)の鳥類における特徴および種差

  中山翔太, 森田鮎子, 池中良徳, 石井千尋, 水川葉月, 武田一貴, 川合佑典, 齊藤慶輔, 渡邊有希子, 大澤夏生, 伊藤真輝, 石塚真由美 日本野生動物医学会大会・講演要旨集 24th 150 2018年08月 [査読無し][通常論文]
  
• 鰭脚類を中心とした食肉目の薬物代謝酵素である硫酸転移酵素の種差解明

  近藤誉充, 池中良徳, 中山翔太, 水川葉月, 三谷曜子, 田辺信介, 野見山桂, 石塚真由美 日本野生動物医学会大会・講演要旨集 24th 151 2018年08月 [査読無し][通常論文]
  
• 国内に生息する野生鳥類における鉛曝露状況の解明

  石井千尋, 池中良徳, 池中良徳, 中山翔太, 齊藤慶輔, 渡辺有希子, 小笠原浩平, 水川葉月, 石塚真由美 日本野生動物医学会大会・講演要旨集 24th 114 2018年08月 [査読無し][通常論文]
  
• PCR法による鳥類の雌雄判定:孵化前雌雄判定の試みとその課題

  中山翔太, 池中良徳, 石井千尋, 水川葉月, 川合佑典, 平野なぎ沙, 齊藤慶輔, 渡邊有希子, 大澤夏生, 伊藤真輝, 中村亮平, 石塚真由美 日本野生動物医学会大会・講演要旨集 24th 138 2018年08月 [査読無し][通常論文]
  
• シスプラチン膀胱内ソノポレーションの前臨床試験的検討

  佐々木 東, 中山 翔太, 大田 寛, 大菅 辰幸, 森下 啓太郎, 水川 葉月, 池中 良徳, 石塚 真由美, 滝口 満喜 日本獣医学会学術集会講演要旨集 161回 429 -429 2018年08月 [査読無し][通常論文]
  
• ザンビア共和国カブウェ鉱床地域における鉛汚染問題:10年間の研究結果と今後の課題

  中山翔太, YABE John, 池中良徳, MUZANDU Kaampwe, CHOONGO Kennedy, 中田北斗, 豊巻治也, BEYENE Yared, KATABA Andrew, ZYAMBO Golden, 栗谷豪, 中川光弘, 水川葉月, 石塚真由美 Journal of Toxicological Sciences 43 (Supplement) S226 2018年06月 [査読無し][通常論文]
  
• 食肉目動物での第II相抱合酵素の遺伝的性状および酵素学的性状の解明

  近藤誉充, 池中良徳, 中山翔太, 水川葉月, 三谷曜子, 野見山桂, 田辺信介, 石塚真由美 Journal of Toxicological Sciences 43 (Supplement) S238 2018年06月 [査読無し][通常論文]
  
• スーパーラットは何が「スーパー」なのか?~東京の殺鼠剤抵抗性クマネズミにおける抵抗性獲得機序の探索~

  武田一貴, 池中良徳, 池中良徳, 田中和之, 中山翔太, 谷川力, 水川葉月, 石塚真由美 Journal of Toxicological Sciences 43 (Supplement) S244 2018年06月 [査読無し][通常論文]
  
• 誘導体化LC/MS/MS法による血漿中のステロイドホルモンおよびその抱合体代謝物35種類の一斉分析法の開発とその応用

  一瀬貴大, 池中良徳, 池中良徳, SAENGTIENCHAI Aksorn, 中山翔太, 水川葉月, 石塚真由美 環境化学討論会要旨集(CD-ROM) 27th ROMBUNNO.P‐086 2018年05月11日 [査読無し][通常論文]
  
• マラリアベクターコントロールにおけるDDTの使用実態とリスク評価

  池中良徳, THOMPSON Lesa, DARWISH Wageh, YOHANNES Yared, VAN VUREN Johan, SMIT Nico, WEPENER Victor, 中山翔太, 水川葉月, 石塚真由美 環境化学討論会要旨集(CD-ROM) 27th ROMBUNNO.2A‐04 2018年05月11日 [査読無し][通常論文]
  
• GPS装置を用いた鉛鉱床地域のイヌの行動のモニタリングと鉛曝露の関係性

  豊巻治也, YABE John, 中山翔太, YARED Beyene, MUZANDU Kaampwe, 水川葉月, 池中良徳, 中田北斗, 石塚真由美 環境化学討論会要旨集(CD-ROM) 27th ROMBUNNO.3C‐06(PA‐54) 2018年05月11日 [査読無し][通常論文]
  
• HPLC‐APCI‐MSを用いたビタミンKの網羅的検出とin vitroビタミンKエポキシド還元酵素活性の評価

  武田一貴, 池中良徳, 池中良徳, 田中和之, 中山翔太, 谷川力, 水川葉月, 石塚真由美 環境化学討論会要旨集(CD-ROM) 27th ROMBUNNO.2B‐01(PA‐22) 2018年05月11日 [査読無し][通常論文]
  
• 野生哺乳類における硫酸転移酵素の動物種差解明

  近藤誉充, 池中良徳, 中山翔太, 水川葉月, 三谷曜子, 田辺信介, 野見山桂, 石塚真由美 環境化学討論会要旨集(CD-ROM) 27th ROMBUNNO.2A‐09(PA‐18) 2018年05月11日 [査読無し][通常論文]
  
• タイ王国におけるペットネコ血清およびペットフード中有機ハロゲン化合物と類縁化合物の汚染実態

  島崎真琴, 野見山桂, 水川葉月, SAENGTIENCHAI Aksorn, NGAMCHIRTTAKUL Araya, PENCHAREE Disdanai, 星野光希, 山本恭央, 高口倖暉, 石塚真由美, 池中良徳, 中山翔太, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 27th ROMBUNNO.2A‐03(PA‐14) 2018年05月11日 [査読無し][通常論文]
  
• ネオニコチノイド系殺虫剤のヒト健康影響評価問題点の整理と今後の研究課題

  池中良徳, 一瀬貴大, NIMAKO Collins, 市川剛, 水川葉月, 中山翔太, 有薗幸司, 石塚真由美 環境化学討論会要旨集(CD-ROM) 27th ROMBUNNO.1C‐16 2018年05月11日 [査読無し][通常論文]
  
• 血清中メタボローム解析によるペットネコ(Felis catus)の有機ハロゲン化合物毒性影響評価

  野見山桂, 江口哲史, 西川博之, 水川葉月, 山本恭央, 滝口満喜, 中山翔太, 池中良徳, 石塚真由美, 田辺信介 環境化学討論会要旨集(CD-ROM) 27th ROMBUNNO.2A‐11 2018年05月11日 [査読無し][通常論文]
  
• 鉛鉱床地域における野生トカゲ亜目の生体内金属類濃度に影響を与える環境要因の解析

  銅谷理緒, 中山翔太, 中田北斗, 豊巻治也, YABE John, MUZANDU Kaampwe, BEYENE Yared, KATABA Andrew, ZYAMBO Golden, 水川葉月, 池中良徳, 石塚真由美 環境化学討論会要旨集(CD-ROM) 27th ROMBUNNO.3C‐05(PA‐53) 2018年05月11日 [査読無し][通常論文]
  
• 非侵襲的に採取可能な乳幼児の糞便における鉛安定同位体比を用いた鉛暴露経路の推定

  中山翔太, 豊巻治也, YABE John, MUZANDU Kaampwe, 中田北斗, 栗谷豪, 中川光弘, 水川葉月, 池中良徳, 石塚真由美 環境化学討論会要旨集(CD-ROM) 27th ROMBUNNO.3C‐08 2018年05月11日 [査読無し][通常論文]
  
• 有機ハロゲン化合物曝露によるネコの生化学マーカーの変化および甲状腺機能に及ぼす影響評価

  水川葉月, KHIDKHAN Kraisiri, 高口倖暉, 横山望, 市居修, 滝口満喜, 笹岡一慶, 池中良徳, 池中良徳, 中山翔太, TSEND‐AYUSH Sainnoxoi, 野見山桂, 田辺信介, 石塚真由美 環境化学討論会要旨集(CD-ROM) 27th ROMBUNNO.2A‐10 2018年05月11日 [査読無し][通常論文]
  
• ネコのin vivo BDE209長期曝露試験による体内動態の解明および甲状腺ホルモンへの影響評価

  田中啓介, 野見山桂, 水川葉月, 高口倖暉, 田上瑠美, 横山望, 市居修, 滝口満喜, 笹岡一慶, 中山翔太, 池中良徳, 石塚真由美, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 27th ROMBUNNO.1A‐03(PA‐13) 2018年05月11日 [査読無し][通常論文]
  
• クロミンククジラ未成熟雌のヒゲ板安定同位体比を用いた摂餌履歴推定

  打田茉由果, 鈴木一平, 石塚真由美, 池中良徳, 中山翔太, 水川葉月, 田村力, 坂東武治, 小西健志, 三谷曜子 日本水産学会大会講演要旨集 2018 44 2018年03月26日 [査読無し][通常論文]
  
• スーパーラットは何が「スーパー」?東京の殺鼠剤抵抗性ラットにおける抵抗性獲得機序の解析

  武田一貴, 池中良徳, 池中良徳, 田中和之, 中山翔太, 谷川力, 石塚真由美 日本分子生物学会年会プログラム・要旨集(Web) 41st ROMBUNNO.3P‐0628 (WEB ONLY) 2018年 [査読無し][通常論文]
  
• 化学汚染の毒性影響の検知

  石塚真由美, 池中良徳, 中山翔太 日本環境化学会講演会予稿集 60th 8 2018年 [査読無し][通常論文]
  
• ポリ塩化ビフェニル曝露によるイヌ・ネコの甲状腺ホルモン恒常性への影響

  高口 倖暉, 中山 翔太, 池中 良徳, 石塚 真由美, 岩田 久人, 国末 達也, 田辺 信介, 野見山 桂, 西川 博之, 水川 葉月, 田上 瑠美, 草木 桃子, 横山 望, 市居 修, 滝口 満喜 日本毒性学会学術年会 45 (0) P -72 2018年 [査読無し][通常論文]
   

  近年、ペット動物に対するポリ塩化ビフェニル（PCBs）および水酸化代謝物（OH-PCBs）の曝露による甲状腺ホルモン（THs）の恒常性への影響が注目されている。本研究ではPCBs曝露がペット動物のTHs恒常性に及ぼす影響を明らかにするため、イヌ・ネコのPCBs投与試験を実施し、PCBs曝露に伴う血清中THs濃度の変化を解析した。

  PCBs投与後から5日間、継続的に血清を採取し、THs濃度の変化を解析した結果、ネコ血清中THs濃度は、総THs、遊離型THsともに対照群と投与群の間に有意な変化は認められなかった。一方、イヌ血清中総THs濃度は投与群において、総L-サイロキシン（T4）と総3,5,3'-トリヨード-L-サイロニン（T3）の減少傾向がみられ、総PCBs濃度は総T4、総T3濃度と有意な負の相関を示した（p < 0.01）。一方、遊離型T4、遊離型T3濃度では、対照群と投与群の間に経時的な変化は認められなかったが、曝露後48、96時間目で有意に増加した（p < 0.05）。加えて、遊離型T4濃度は総OH-PCBs濃度と正の相関を示し（p < 0.01）、異性体別ではT4様構造の高塩素化OH-PCBsで同様の傾向が認められた。上記の結果および先行研究から、PCBs曝露によるイヌ血清中THsへの影響を推察した。PCBsがT4様構造のOH-PCBsへ代謝されてTHs輸送タンパクに競合結合し、結合できない遊離型T4が血中に増加することで、THsの臓器・組織への取り込み量が増加したと予測される。その結果、イヌ肝臓中のTHs濃度は増加し、PCBs曝露により肝臓中のAhR・CARが過剰に誘導されることで、UGTおよびSULTが誘導され、THsの抱合化を促進することで体外排泄量が増加し、血清中総T4、T3が減少したものと推察された。

• 幼児および新生児におけるネオニコチノイド系殺虫剤の曝露実態

  池中良徳, 宮原裕一, 一瀬貴大, 中山翔太, 水川葉月, 市川剛, 遠山千春, 石塚真由美 日本内分泌かく乱化学物質学会研究発表会要旨集 20th 44 2017年12月 [査読無し][通常論文]
  
• ポリ塩化ビフェニル(PCBs)がネコの甲状腺機能に及ぼす影響

  水川 葉月, 高居 名菜, 野見山 桂, 高口 倖暉, 横山 望, 市居 修, 滝口 満喜, 池中 良徳, 中山 翔太, 石塚 真由美 環境ホルモン学会研究発表会要旨集 20回 78 -78 2017年12月 [査読無し][通常論文]
  
• 鳥類で起こっているケミカルハザードとそのメカニズム (特集 野生鳥類の化学物質汚染とその影響 : 第21回日本野生動物医学会大会学会主催シンポジウム)

  中山 翔太, 水川 葉月, 池中 良徳, 石塚 真由美 日本野生動物医学会誌 = Japanese journal of zoo and wildlife medicine 22 (4) 69 -72 2017年12月 [査読無し][通常論文]
   

  <p> 化学物質が引き起こす被害「ケミカルハザード」は，鳥類においても報告されているが，その実態やメカニズムには不明な点も多い。シンポジウムでは鳥類において懸念されるケミカルハザードについて「重金属」と「殺鼠剤」を取り上げ，これまでの研究成果を報告した。本稿では，殺鼠剤に関して報告する。ドブネズミなどの外来性小哺乳類は，公衆衛生学的理由のほか，生態系を攪乱することから，その駆除のために殺鼠剤が使用されている。1950年代より，安全性を考慮して，ビタミンKエポキシド還元酵素を標的とした殺鼠剤が世界的に使用されている。一方で，ニワトリについて殺鼠剤への感受性が極めて低いため，鳥類では中毒が起こりにくいと考えられてきた。しかしながら，これまでの我々の研究で，鳥類では種によってこの殺鼠剤に対する感受性が大きく異なることがわかってきた。殺鼠剤の感受性種差についてその分子メカニズムを明らかにした研究はない。基礎的なデータ基盤が欠落したまま殺鼠剤を使用することにより，海外では外来性のげっ歯類駆除のために散布された殺鼠剤により，離島で8割の海鳥種が全滅したことも報告されている。また近年加速する猛禽類の生息数の減少の主要因の1つとして，この殺鼠剤による環境及び餌生物の汚染が挙げられている。現在，国内では離島の野生げっ歯類の駆除のために，鳥類での感受性が低いことを前提に殺鼠剤が用いられている。ここでは鳥類の殺鼠剤感受性と毒性メカニズムの一端を紹介する。</p>
• 高次栄養段階生物への化学物質の感受性の種差

  石塚真由美, 中山翔太, 水川葉月, 池中良徳 Endocrine Disrupter News Letter 20 (3) 4 2017年12月 [査読無し][通常論文]
  
• 鳥類医学の発展に向けた新規腎障害マーカーの探索

  石井千尋, 池中良徳, 川合佑典, 市居修, 中山翔太, 水川葉月, 石塚真由美 日本鳥学会大会講演要旨集 2017 100 2017年09月15日 [査読無し][通常論文]
  
• 海鳥を介した汚染物質輸送

  庄子晶子, ELLIOTT K, ARIS‐BROSOU S, 水川葉月, 中山翔太, 池中良徳, 石塚真由美, 桑江朝比呂, 渡辺謙太, 綿貫豊 日本鳥学会大会講演要旨集 2017 70 2017年09月15日 [査読無し][通常論文]
  
• 鳥類におけるグルクロン酸抱合能の種差の解明と化学物質感受性の推定

  新屋惣, 池中良徳, 中山翔太, 水川葉月, 伊藤真輝, 高江洲昇, 齊藤慶輔, 渡邉有希子, 石塚真由美 日本鳥学会大会講演要旨集 2017 105 2017年09月15日 [査読無し][通常論文]
  
• 東京由来殺鼠剤抵抗性ラットを用いた新規抵抗性獲得機序の解明:ペントースリン酸経路の亢進による殺鼠剤代謝能の活性化

  武田一貴, 池中良徳, 田中和之, 中山翔太, 谷川力, 水川葉月, 石塚真由美 日本獣医学会学術集会講演要旨集 160th 504 2017年08月30日 [査読無し][通常論文]
  
• 超音波と膀胱内注入療法を組み合わせた膀胱癌治療法の開発

  佐々木 東, 中山 翔太, 森下 啓太郎, 中村 健介, 大田 寛, 水川 葉月, 池中 良徳, 石塚 真由美, 滝口 満喜 日本獣医学会学術集会講演要旨集 160回 461 -461 2017年08月 [査読無し][通常論文]
  
• ソノポレーションを用いた膀胱内注入療法の開発 (特集 進化する超音波治療技術の最前線(1))

  佐々木 東, 工藤 信樹, 中山 翔太, 滝口 満喜 超音波techno 29 (4) 27 -30 2017年07月 [査読無し][通常論文]
  
• ポリ塩化ビフェニル(PCBs)暴露によるネコ甲状腺機能への影響評価~甲状腺ホルモンの脱ヨード化と代謝能の解析~

  水川葉月, 高居名菜, 横山望, 市居修, 滝口満喜, 野見山桂, 高口倖暉, 西川博之, 池中良徳, 池中良徳, 中山翔太, SAINNOXOI Tsend‐ayush, 田辺信介, 石塚真由美 環境化学討論会要旨集(CD-ROM) 26th ROMBUNNO.2A‐01 2017年06月05日 [査読無し][通常論文]
  
• PCBs曝露がイヌ・ネコの甲状腺ホルモン恒常性へ及ぼす影響

  高口倖暉, 野見山桂, 西川博之, 水川葉月, 田上瑠美, 芳之内結加, 横山望, 市居修, 滝口満喜, 中山翔太, 池中良徳, 石塚真由美, 岩田久人, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 26th ROMBUNNO.2A‐02 2017年06月05日 [査読無し][通常論文]
  
• イエネコのin vivo長期曝露試験:デカブロモジフェニルエーテル(BDE209)は甲状腺機能亢進症を引き起こすのか?

  水川葉月, 野見山桂, 池中良徳, 池中良徳, 中山翔太, SAENGTIENCHAI Aksorn, SAINNOXOI Tsendayush, 横山望, 笹岡一慶, 市居修, KHIDKHAN Kraisiri, 高居名菜, 滝口満喜, 田辺信介, 石塚真由美 環境化学討論会要旨集(CD-ROM) 26th ROMBUNNO.2A‐03 2017年06月05日 [査読無し][通常論文]
  
• 幼児における尿中ネオニコチノイド濃度とその曝露実態の解明

  池中良徳, 池中良徳, 宮原裕一, 一瀬貴大, 八木橋美緒, 中山翔太, 水川葉月, 遠山千春, 石塚真由美 環境化学討論会要旨集(CD-ROM) 26th ROMBUNNO.3C‐03 2017年06月05日 [査読無し][通常論文]
  
• 血清中メタボローム解析によるイエネコのPCBs毒性影響評価

  野見山桂, 西川博之, 水川葉月, 高口倖暉, SAINNOXOI Tsend‐ayush, 横山望, 市居修, 滝口満喜, 石塚真由美, 池中良徳, 中山翔太, 江口哲史, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 26th ROMBUNNO.2A‐05 2017年06月05日 [査読無し][通常論文]
  
• In situ肝灌流試験によるワルファリン抵抗性クマネズミでのワルファリン代謝能の解明

  武田一貴, 池中良徳, 田中和之, 中山翔太, 谷川力, 水川葉月, 石塚真由美 環境化学討論会要旨集(CD-ROM) 26th ROMBUNNO.P‐218 2017年06月05日 [査読無し][通常論文]
  
• ヒト生体試料を用いたネオニコチノイドおよびネオニコチノイド代謝物の分析方法

  一瀬貴大, 池中良徳, 池中良徳, 藤岡一俊, 平久美子, 中山翔太, 水川葉月, 八木橋美緒, 有薗幸司, 加藤恵介, 高橋圭介, 石塚真由美 環境化学討論会要旨集(CD-ROM) 26th ROMBUNNO.P‐093 2017年06月05日 [査読無し][通常論文]
  
• イエネコのin vivo長期曝露試験:デカブロモジフェニルエーテル(BDE209)の生体内変化

  田中啓介, 野見山桂, 水川葉月, 高口倖暉, 田上瑠美, SAENGTIENCHAI Aksorn, SAINNOXOI Tsend‐ayush, 横山望, 市居修, 滝口満喜, 中山翔太, 池中良徳, 石塚真由美, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 26th ROMBUNNO.2A‐04 2017年06月05日 [査読無し][通常論文]
  
• Contamination status and accumulation characteristics of heavy metals and arsenic in five seabird species from the central Bering Sea

  Chihiro Ishii, Yoshinori Ikenaka, Shouta M. M. Nakayama, Hazuki Mizukawa, Yared Beyene Yohannes, Yutaka Watanuki, Masaaki Fukuwaka, Mayumi Ishizuka JOURNAL OF VETERINARY MEDICAL SCIENCE 79 (4) 807 -814 2017年04月 [査読無し][通常論文]
   

  Seabirds are marine top predators and accumulate high levels of metals and metalloids in their tissues. Contamination by metals in the highly productive offshore region has become a matter of public concern. It is home to 80% of the seabird population in the U.S.A., 95% of northern fur seals (Callorhinus ursinus), and major populations of Steller sea lions (Eumetopias jubatus), walruses (Odobenus rosmarus) and whales. Here, the concentrations of eight heavy metals (Hg, Cd, Cr, Co, Ni, Cu, Zn and Pb) and a metalloid (As) in the liver and kidneys of the northern fulmar (Fulmarus glacialis), thick-billed murre (Uria lomvia), short-tailed shearwater (Puffinus tenuirostris), tufted puffin (Fratercula cirrhata) and horned puffin (Fratercula corniculata) collected in the Bering Sea were measured. As proxies of trophic level and habitat, nitrogen (delta N-15) and carbon (delta C-13) stable isotope ratios of breast muscles were also measured. Hepatic Hg concentration was high in northern fulmar, whereas Cd level was high in tufted puffin and northern fulmar. The Hg concentration and d15N value were positively correlated across individual birds, suggesting that Hg uptake was linked to the trophic status of consumed prey. Furthermore, Hg concentration in our study was higher than those of the same species of seabirds collected in 1990.
• クロミンククジラ妊娠雌のヒゲ板の安定同位体比を用いた摂餌履歴推定

  打田茉由果, 伊藤慶造, 石塚真由美, 池中良徳, 中山翔太, 水川葉月, 坂東武治, 田村力, 小西健志, 鈴木一平, 三谷曜子 日本水産学会大会講演要旨集 2017 24 2017年03月26日 [査読無し][通常論文]
  
• 8-2-5 Multidisciplinary field research in Kabwe, Zambia, towards better understanding of lead contamination of the city - A short report from a field survey（8-2 地球環境，2017年度仙台大会）

  好井 優衣, 内田 義崇, Kawawa Banda, 濱本 亨, Kabenuka Munthali, Mukuka Mwansa, Yabe John, 石塚 真由美, 中山 翔太 日本土壌肥料学会講演要旨集 63 (0) 168 -168 2017年 [査読無し][通常論文]
  
• 陸棲哺乳類の血中に残留する臭素化フェノール類の曝露源解明と感受性の種差

  水川 葉月, 野見山 桂, 田辺 信介, 池中 良徳, 中山 翔太, 石塚 真由美 日本毒性学会学術年会 44 (0) S4 -4 2017年 [査読無し][通常論文]
   

  臭素系難燃剤であるポリ臭素化ジフェニルエーテル（PBDEs）は、薬物代謝酵素の働きにより水酸化PBDEs（OH-PBDEs）に代謝され、酵素による抱合作用を受けた後、体外へ排泄される。近年、OH-PBDEsの曝露経路にはPBDEsの曝露とその水酸化代謝由来に加え、海藻やシアノバクテリアなどが生成する海洋天然生成物の取り込みが重要視されている。また、同じく海洋天然生成物であるメトキシPBDEs（MeO-PBDEs）を体内に取り込み、脱メチル化によりOH-PBDEsが生成することも報告されている。さらに、ブロモフェノール（BPhs）も難燃剤など工業用製剤として使用され、海洋天然起源の生成物としても報告されている。OH-PBDEsやBPhsは甲状腺ホルモンと類似の構造を持つことから、血中の甲状腺ホルモン輸送タンパクに競合的に結合し、甲状腺ホルモンの恒常性撹乱や脳神経系への悪影響を引き起こすことが懸念されている。<br>本研究では、ネコやイヌなど陸棲哺乳類の血中に残留するハロゲン化フェノール類を分析し、汚染実態や残留特性、リスクについて考察した。その結果、全ての陸棲哺乳類の血中から天然および人工起源の臭素化フェノール類が検出され、特にネコで高値であった。また、検出された異性体組成から生体内の臭素化フェノール類の大部分は、餌から取り込んだPBDEsや天然起源のMeO-PBDEsが体内で変化した代謝生成物であると推察された。とくに、海産物を主原料とするキャットフードでは高濃度のMeO-PBDEsやBPhsが検出され、主要な曝露源となっていることが判明した。ネコではグルクロン酸抱合酵素の欠損による水酸化代謝物の感受性は高いことが予想され、本種はハロゲン化フェノール類のハイリスクアニマルであることが推察される。元来陸棲の肉食種であるイエネコに魚類を原料とするペットフードを与えることで、ネコの健康悪影響を引き起こしている可能性も考えられ、更なるリスク評価が重要課題と考えられた。
• ネコの甲状腺機能に対するポリ塩化ビフェニル（PCBs）の影響評価～甲状腺ホルモンの脱ヨード化と代謝能の解析～

  水川 葉月, 中山 翔太, Tsend-ayush SAINNOXOI, 田辺 信介, 石塚 真由美, 高居 名菜, 横山 望, 市居 修, 滝口 満喜, 野見山 桂, 高口 倖暉, 西川 博之, 池中 良徳 日本毒性学会学術年会 44 (0) P -55 2017年 [査読無し][通常論文]
   

  有機ハロゲン化合物の一種であるポリ塩化ビフェニル（PCBs）は甲状腺ホルモン（THs）の恒常性かく乱が懸念されており、実際、ヒトやげっ歯類においてはPCBs暴露により血中THs濃度の低下が認められている。ヒトの身近な動物であるネコは餌などを介してPCBsに暴露していると懸念され、THs恒常性に何らかの悪影響をもたらすことが予想される。本研究では、ネコの甲状腺機能に対するPCBsの影響を解析するため、in vivo投与試験したネコを用いて甲状腺機能への影響を解析した。血中のTHs濃度（総T4、総T3、遊離T4、遊離T3、リバースT3）を解析した結果、対照群と暴露群の間に有意な差は見られなかった。また、THsの恒常性に関与する遺伝子（甲状腺ホルモン受容体αおよびβ、脱ヨード酵素type1）の肝臓中発現量やTHs代謝に関わる酵素であるグルクロン酸抱合酵素（UGT1A1）の活性を調べたところ、対照群と暴露群の間に有意な差は見られなかった。
  本実験結果では、ネコにおいてPCBs短期暴露によるTHsへの影響が認められなかったが、日本のペットネコにおけるモニタリング調査では、血中のTHs濃度とPCBs濃度との間に負の相関が見られており、有機ハロゲン化合物によるTHsかく乱が懸念されている。また、本研究試料のメタボローム解析結果では酸化ストレスの発現、抗酸化物質、電子伝達物質の生産阻害などが示唆されており、PCBsや水酸化代謝物による内分泌撹乱作用が心配される。THsの恒常性は非常に複雑な機構のもと維持されていることが知られており、負のフィードバック機構に加え、THsの活性化や代謝、排泄の調整にも多くの遺伝子やトランスポーター、酵素など様々な要因が関わっていることから、ネコは長期的かつ慢性的に化学物質に暴露されることで、甲状腺機能などへの悪影響が現れると考えられ、内分泌撹乱作用の作用機序について解析を進めることが重要である。
• In situ肝灌流試験、in vitro酵素活性試験による東京由来ワルファリン抵抗性クマネズミのワルファリン代謝能の解明

  武田 一貴, 池中 良徳, 田中 和之, 中山 翔太, 谷川 力, 水川 葉月, 石塚 真由美 日本毒性学会学術年会 44 (0) P -21 2017年 [査読無し][通常論文]
   

  ワルファリン(Wf)等の抗凝血作用を持つ物質は殺鼠剤として広く用いられてきた。しかし、これらに対し抵抗性を持つ個体群が殺鼠剤使用頻度の高い世界各地の都市部に出現している。現在抵抗性ラットに有効な防除策は乏しく、新規防除策提案のため抵抗性獲得機序の解明は急務である。<br> 抵抗性ラットでは、Wfの標的分子ビタミンKエポキシド還元酵素（VKOR）に遺伝子変異が生じ、VKORのWf感受性が低下していることが報告された(Rost 2004 Nature 427:537–41)。しかし各地の抵抗性群は異なる変異パターンを有し、VKOR変異以外の抵抗性獲得機序の存在も疑われる。著者らが東京の殺鼠剤抵抗性ラットでのWfの体内動態を解析した所、抵抗性群は高いWf排泄能を有しており、代謝が抵抗性に関与する事が示唆された。(Takeda et al. 2016 Pestic Biochem Physiol. 134:1-7)<br>目的・方法：Wfは肝臓で薬物代謝酵素シトクロムP450 (CYPs)により水酸化され代謝される。そこで、抵抗性ラット肝臓におけるWf代謝能解明を目的に下記の実験を実施した。東京由来Wf抵抗性野生クマネズミのクローズドコロニーを用い、<i>in situ</i> Wf肝灌流試験を行い、生体に近い条件での代謝能を評価した。またCYPが局在するミクロソーム画分を肝臓より抽出し、<i>in vitro</i>での酵素活性も測定した。ミクロソーム中CYPs発現量はウェスタンブロットにて定量した。<br>結果・考察：<i>In situ</i>肝灌流試験では今回定量した5種全てのWf水酸化体において抵抗性群が感受性群より5～10倍程度有意に高い値を示した。また、<i>in vitro </i>Wf代謝活性でも抵抗性群は感受性群より有意に高い酵素活性を示し、CYPs発現量も有意に高い傾向であった。しかし、その差はいずれも1.3倍程度と肝灌流よりも小さかった。この結果から抵抗性ラットはWfの高代謝能を有するが、その要因はCYPsではなく<i>in vitro</i>試験では観察できなかった電子伝達系等に存在することが示唆された。
• 幼児に対するネオニコチノイド系殺虫剤の曝露評価

  池中 良徳, 加藤 恵介, 遠山 千春, 石塚 真由美, 宮原 裕一, 一瀬 貴大, 八木橋 美緒, 中山 翔太, 水川 葉月, 平 久美子, 有薗 幸司, 高橋 圭介 日本毒性学会学術年会 44 (0) O -20 2017年 [査読無し][通常論文]
   

  ネオニコチノイド系殺虫剤は、哺乳類における体内蓄積性は短く、昆虫とヒトのニコチン受容体に対する親和性の違いから、ヒトに対する毒性は相対的に低いため、一定の基準以下であれば、日常生活においてその毒性は無視できると考えられている。しかし、日本では諸外国と比べ数倍～数十倍と果物や野菜、茶葉における食品残留基準値が高く設定されていること、また、記憶・学習などの脳機能に及ぼす影響をはじめ、発達神経毒性には不明な点が多いことなどから、健康に及ぼす懸念が払拭できていない。とりわけ、感受性が高いこどもたちや化学物質に過敏な人々の健康へのリスクを評価するためには、ネオニコチノイドが体内にどの程度取り込まれているかを把握することがまず必要である。そこで本調査では、長野県上田市の松くい虫防除が行われている地域の住民のうち、感受性が高いと考えられる小児（3歳～6歳）から尿を採取し、尿中のネオニコチノイドおよびその代謝物を測定することで、曝露評価を行う事を目的とした。当該調査では、松枯れ防止事業に用いる薬剤（エコワン３フロワブル、主要成分：Thiacloprid）の散布時期の前後に、46人の幼児から提供された尿試料中のネオニコチノイドとその代謝産物を測定した。また、同時に大気サンプルもエアーサンプラーを用いて採取し、分析に供した。分析した結果、Thiaclopridは検出頻度が30％程度であり、濃度は
• Studies on polycyclic aromatic hydrocarbons formation in heat-treated meat

  DARWISH Wageh Sobhy, IKENAKA Yoshinori, NAKAYAMA Shouta M.M, MIZUKAWA Hazuki, ISHIZUKA Mayumi 日本毒性学会学術年会 44 (0) O -15 2017年 [査読無し][通常論文]
   

  Polycyclic aromatic hydrocarbons (PAHs) are wide spread as environmental pollutants, which can be generated during the preparation of food. Food is the main source of exposure to PAHs for people who do not smoke. Epidemiological studies indicate that diets rich in fruits and vegetables can be associated with lower risks of numerous diseases and cancers. However, the exact mechanisms behind these effects are still unclear. The objectives of this study were firstly to estimate PAHs contents in some heat-treated meat samples collected from different localities in Egypt. Secondly, to investigate the mutagenic activities for some of the formed PAHs. Finally, to investigate the protective effects and mechanism of action of some micronutrients against the adverse effects of PAHs. <br> Polycyclic aromatic hydrocarbons were measured in heat-treated meat collected from different localities in Egypt using HPLC. Mutagenic activities of some formed PAHs were examined using Ames Salmonella typhimurium mutagenicity assay. Human HepG2 cells were exposed to environmental-relevant concentrations of some formed PAHs. Modulation of xenobiotic metabolizing enzymes (XMEs) mRNA expressions was investigated using real-time qPCR.<br> The results of this study indicated the formation of different PAHs in heat-treated meat with variable concentrations. Some of the formed PAHs had clear mutagenic activities such as benzo[a]pyrene. Obtained results declare the protective effects of carotenoids like β-carotene and retinoids like retinol against B[a]P induced adverse effects. Modulation of XMEs is proposed to be a possible mechanism for this protection. In conclusion, consumption of β-carotene and retinol in the areas of high PAH pollution is recommended.
• 全国規模での鳥類への鉛曝露:曝露指標として骨の利用の可能性

  石井千尋, 中山翔太, 池中良徳, ANDREW Kataba, 齊藤慶輔, 渡辺有希子, 槇納好岐, 松川岳久, 久保田章乃, 横山和仁, 水川葉月, 平田岳史, 石塚真由美 日本野生動物医学会大会・講演要旨集 23rd 81 2017年 [査読無し][通常論文]
  
• エストロジェン類高感度分析法の開発と野生動物におけるスクリーニング

  新屋惣, 池中良徳, 中山翔太, 石井千尋, 水川葉月, 伊藤真輝, 高江洲昇, 大澤夏生, 綿貫豊, 石塚真由美 日本野生動物医学会大会・講演要旨集 23rd 125 2017年 [査読無し][通常論文]
  
• 薬物代謝酵素の動物種差

  石塚真由美, 中山翔太, 水川葉月, 池中良徳 日本薬学会年会要旨集(CD-ROM) 137th ROMBUNNO.S45‐4 2017年 [査読無し][通常論文]
  
• 東京のワルファリン抵抗性ラットの抵抗性獲得機序の解明:ペントースリン酸経路の亢進を通したワルファリン代謝の活性化

  武田一貴, 池中良徳, 池中良徳, 田中和之, 中山翔太, 谷川力, 水川葉月, 石塚真由美 日本生化学会大会(Web) 90th ROMBUNNO.3AT12‐14(3P‐0236) (WEB ONLY) 2017年 [査読無し][通常論文]
  
• 鳥類の鉛中毒の分析と原因 (特集 野生動物の鉛中毒 : 希少猛禽類の鉛中毒を中心に)

  石井 千尋, 中山 翔太, 水川 葉月, 池中 良徳, 石塚 真由美 The Japanese journal of clinical toxicology = 中毒研究 : 日本中毒学会機関誌 30 (4) 363 -367 2017年 [査読無し][通常論文]
  
• 野生げっ歯類の殺鼠剤の抵抗性メカニズムと非対象動物に対する毒性メカニズム

  石塚真由美, 中山翔太, 水川葉月, 池中良徳 日本哺乳類学会大会プログラム・講演要旨集 2016 56 2016年09月23日 [査読無し][通常論文]
  
• 野生動物の化学物質蓄積や感受性の種差

  石塚真由美, 中山翔太, 水川葉月, 池中良徳 日本獣医学会学術集会講演要旨集 159th 293 2016年08月30日 [査読無し][通常論文]
  
• 野生動物及び実験動物におけるグルクロン酸抱合酵素の動物種差解明

  近藤誉充, 池中良徳, 中山翔太, 水川葉月, SAENGTIENCHAI Aksorn, BEYENE Yared, 坂本健太郎, 和田昭彦, 服部薫, 三谷曜子, 田辺信介, 野見山桂, 石塚真由美 日本獣医学会学術集会講演要旨集 159th 493 2016年08月30日 [査読無し][通常論文]
  
• 家畜・家禽の鉛安定同位体生体内分別の種差および歩哨動物としての有用性評価

  栂尾正雄, 中山翔太, YABE John, 池中良徳, 中田北斗, 石井千尋, 水川葉月, BEYENE Yared, SAENGTIENCHAI Aksorn, 石塚真由美 日本獣医学会学術集会講演要旨集 159th 494 2016年08月30日 [査読無し][通常論文]
  
• ヒト尿中のネオニコチノイドおよびその代謝産物の分析法の確立とヒトへの曝露評価

  池中良徳, 池中良徳, 藤岡一俊, 平久美子, 中山翔太, 水川葉月, 一瀬貴大, MARFO Jemima Tiwaa, 有薗幸司, 加藤恵介, 石坂真澄, 馬場浩司, 川上智規, 石塚真由美 環境化学討論会要旨集(CD-ROM) 25th ROMBUNNO.1A‐07 2016年06月06日 [査読無し][通常論文]
  
• メタボローム解析を用いたイエネコにおけるPCBsの毒性影響評価

  西川博之, 野見山桂, 水川葉月, 横山望, 市居修, 滝口満喜, 石塚真由美, 池中良徳, 中山翔太, 江口哲史, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 25th ROMBUNNO.1A‐12 2016年06月06日 [査読無し][通常論文]
  
• 有機ハロゲン化合物によるコンパニオンアニマルの汚染実態と甲状腺ホルモンへの影響評価

  野見山桂, 山本恭央, 水川葉月, 江口哲史, 滝口満喜, 中山翔太, 池中良徳, 石塚真由美, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 25th ROMBUNNO.1A‐14 2016年06月06日 [査読無し][通常論文]
  
• ネコにおけるポリ塩化ビフェニル(PCBs)の異物代謝機構解明と甲状腺ホルモンへの影響評価

  水川葉月, 前原美咲, 横山望, 市居修, 滝口満喜, 野見山桂, 西川博之, 池中良徳, 中山翔太, 高口倖暉, 田辺信介, 石塚真由美 環境化学討論会要旨集(CD-ROM) 25th ROMBUNNO.1A‐13 2016年06月06日 [査読無し][通常論文]
  
• 脂肪組織における芳香族炭化水素受容体(AhR)の機能解明

  本平航大, 池中良徳, DARWICH Wageh S, 中山翔太, 水川葉月, 石塚真由美 Journal of Toxicological Sciences 41 (Supplement) S255 -84 2016年06月 [査読無し][通常論文]
   

  【はじめに】AhR(芳香族炭化水素受容体)はシトクロムP450をはじめとした種々の薬物代謝酵素を誘導することで異物の代謝に関与する受容体として研究が進められてきた。近年、従来主要な役割であると考えられてきた異物の代謝に加え、成長因子、抗酸化因子、炎症物質などを誘導するといった新たな生体内での役割が注目を集めている。AhRは肝臓や肺といった異物代謝活性が高い組織で活性が高く、上記に挙げた新たなAhRの働きの研究がなされているのに対し、薬物の「蓄積」という特徴的な応答を示す脂肪組織における反応は未知の部分が多い。そこで本研究では脂肪組織におけるAhRの働きを探求するとともに他組織との比較を試みた。<br>【方法】脂肪組織としてヒト脂肪由来幹細胞、肝臓組織としてヒト肝癌由来細胞を用い、AhRのリガンドと考えられているβ-naphthoflavoneを含む複数の化学物質を暴露した。これらの暴露細胞から抽出、精製したcDNAを用いて比較リアルタイムPCR法により各組織における異物代謝酵素と成長因子をはじめとした異物代謝とは直積関与するわけではない遺伝子の発現量を暴露-被暴露間、肝-脂肪細胞間で比較した。<br>【結果と考察】AhRリガンド暴露の結果、ヒト脂肪由来幹細胞、ヒト肝癌細胞の何れの細胞においてもCYP1A1や成長因子である繊維芽細胞増殖因子(fgf2など)の発現量の増加が確認された。種々の遺伝子で脂肪由来幹細胞と肝癌細胞の間で反応性や遺伝子発現量に違いが確認された。この結果から一般的に肝臓で誘導が認められている遺伝子に関して、脂肪組織でも誘導されていることが明らかになった。また今回観察を行った繊維芽細胞増殖因子では複数のサブファミリーがAhRリガンドにより誘導されており、繊維芽細胞増殖因子の全てのサブファミリーがAhRの支配を受けていることが示唆された。本研究の結果、種々の遺伝子で脂肪由来幹細胞-肝癌細胞間に反応性や遺伝子発現量に差が見られ、これが脂肪組織におけるAhRの他組織における働きとの違いと推測出来た。
• 東京由来ワルファリン抵抗性クマネズミクローズドコロニーでのワルファリン体内動態の解明

  武田一貴, 池中良徳, 田中和之, 谷川力, 中山翔太, 水川葉月, 石塚真由美 Journal of Toxicological Sciences 41 (Supplement) S257 -89 2016年06月 [査読無し][通常論文]
   

  ワルファリンは抗凝血作用を示す化学物質であり、その薬効はビタミンK依存性血液凝固因子合成に不可欠なビタミンKエポキシド還元酵素 (VKOR)の阻害により発揮される。ワルファリンを含む種々の抗凝血薬は殺鼠剤として広く用いられているが、世界中の都市部でワルファリンに対し抵抗性を持つ野生齧歯類の棲息が確認されており、東京では棲息数の80%を占める地域すら存在する。これら野生齧歯類は重篤な人獣共通感染症を媒介するため、抵抗性獲得機序の解明は急務であるといえる。抵抗性の原因としてワルファリンの標的分子：VKORに遺伝子変異が生じ、それに伴いVKORのワルファリン感受性が低下する事が報告されている。しかしVKOR変異が生体レベルでどの程度抵抗性へ寄与するか不明な点も多くVKOR以外の抵抗性獲得機序が疑われている。そこでVKOR変異以外の要因を探索するため、筆者らは東京由来ワルファリン抵抗性野生クマネズミクローズドコロニーを確立し、その個体群を用いワルファリン経口投与後体内薬物動態解析を行った。その結果、抵抗性群ではワルファリン投与後のAUC(血漿中濃度－時間曲線下面積)、肝臓腎臓中蓄積濃度が感受性群に比べ有意に低く、一方で消失速度を示すクリアランスは有意に高かった。またワルファリンの代謝産物である水酸化ワルファリンの血漿中濃度は、抵抗性群において投与後1時間と非常に迅速に最高濃度に達し（感受性群では投与後6時間前後）、尿中への排泄量も水酸化体の一分子種(4’水酸化体)で有意に増加していた。このワルファリン代謝を担っているシトクロムP450分子種の肝ミクロソーム中タンパク発現量は抵抗性群では有意に高かった。<br>これらの結果は東京のワルファリン抵抗性個体群ではワルファリンの代謝・排泄能が亢進している事を示唆し、それによる迅速な解毒が抵抗性に寄与しているものと考えられる。
• UGTの動物種差

  石塚真由美, 中山翔太, 水川葉月, 池中良徳 Journal of Toxicological Sciences 41 (Supplement) S106 -4 2016年06月 [査読無し][通常論文]
   

  外来性化学物質代謝の第II相反応では、第I相反応の代謝物の極性をさらに増加させるグルクロン酸抱合（UGT）や硫酸抱合（SULT）、グルタチオン抱合酵素などの抱合反応が主要な代謝となっている。化学物質の代謝能力は、生物の化学物質に対する感受性を決定する重要なファクターである。我々はこれまでの研究から、魚類から哺乳類まで、P450および第II相反応の抱合に大きな動物種差があることを報告してきた。<br>哺乳類ではUGT1ファミリーは、主に内因性物質を代謝するビリルビングループ(1A1-1A5)と外因性物質を代謝するフェノールグループ(UGT1A6-1A10)に大別される。我々は、食肉目を中心とした哺乳類におけるUGT1ファミリーの遺伝子解析を行ったところ、鰭脚類は外因性物質であるアセトアミノフェン及び1－ヒドロキシピレンに対するUGT活性がネコと同程度に低く、中でもトドおよびキタオットセイではUGT1A6の偽遺伝子化が明らかになった。またUGT1ファミリーの系統解析及びシンテニー解析の結果、哺乳類のUGT1ファミリーは内因性物質代謝を担うUGT1A1相同遺伝子及び外因性物質代謝を担うUGT1A6相同遺伝子がそれぞれ遺伝子重複した後、動物種ごとに独自に遺伝子重複/欠損が起き、UGT1A2-1A5及びUGT1A7-1A10遺伝子が形成されたことが示唆された。一方、UGTと基質特異性が一部重複するSULTに関しては、これまで教科書的にブタで活性が欠損しているとされてきたが、ブタの肝臓ミクロソームのKm/Vmaxによる酵素効率の比較では他の動物種と大きな差はないことや、新たに硫酸抱合酵素が低活性である哺乳類を同定した<br>そこで、今回、動物が有する化学物質代謝の種差と毒性発現の違いを、UGTを中心に紹介したい。
• Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats

  Yoshihiro Nishiyama, Shouta M. M. Nakayama, Kensuke P. Watanabe, Yusuke K. Kawai, Marumi Ohno, Yoshinori Ikenaka, Mayumi Ishizuka JOURNAL OF VETERINARY MEDICAL SCIENCE 78 (4) 675 -680 2016年04月 [査読無し][通常論文]
   

  Rat cytochrome P450 (CYP) exhibits inter-strain differences, but their analysis has been scattered across studies under different conditions. To identify these strain differences in CYP more comprehensively, mRNA expression, protein expression and metabolic activity among Wistar (WI), Sprague Dawley (SD), Dark Agouti (DA) and Brown Norway (BN) rats were compared. The mRNA level and enzymatic activity of CYP1A1 were highest in SD rats. The rank order of Cyp3a2 mRNA expression mirrored its protein expression, i.e., DA>BN>SD>WI, and was similar to the CYP3A2-dependent warfarin metabolic activity, i.e., DA>SD>BN>WI. These results suggest that the strain differences in CYP3A2 enzymatic activity are caused by differences in mRNA expression. Cyp2b1 mRNA levels, which were higher in DA rats, did not correlate with its protein expression or enzymatic activity. This suggests that the strain differences in enzymatic activity are not related to Cyp2b1 mRNA expression. In conclusion, WI rats tended to have the lowest CYP1A1, 2B1 and 3A2 mRNA expression, protein expression and enzymatic activity among the strains. In addition, SD rats had the highest CYP1A1 mRNA expression and activity, while DA rats had higher CYP2B1 and CYP3A2 mRNA and protein expression. These inter-strain differences in CYP could influence pharmacokinetic considerations in preclinical toxicological studies.
• Feather mercury concentration in streaked shearwaters wintering in separate areas of southeast Asia

  Yutaka Watanuki, Ai Yamashita, Mayumi Ishizuka, Yoshinori Ikenaka, Shouta M. M. Nakayama, Chihiro Ishii, Takashi Yamamoto, Motohiro Ito, Tomohiro Kuwae, Philip N. Trathan MARINE ECOLOGY PROGRESS SERIES 546 263 -269 2016年03月 [査読無し][通常論文]
   

  We measured mercury concentration ([Hg]) and nitrogen stable isotope values (delta N-15) in tail feathers that were replaced during the non-breeding period of streaked shearwaters Calonectris leucomelas that bred on 3 islands in Japan. The birds' year-round movements were tracked and their breeding status was monitored. [Hg] was greater in males than in females, and was greatest in those birds spending their non-breeding period in the South China Sea (3.1 +/- 1.5 mu g g(-1) dry weight), moderate in birds in the Arafura Sea (1.5 +/- 0.7 mu g g(-1)), and lowest in birds in the Pacific Ocean north of New Guinea (0.8 +/- 0.4 mu g g(-1)). Adverse effects of feather [Hg] on breeding status were not observed. This regional variation in feather [Hg] might partly reflect differences in the intake of Hg between these non-breeding areas in addition to accumulation during the late breeding period and the southward migration period.
• ハリネズミは化学物質高感受性種？African hedgehog (Atalerix albiventris)で観察された低薬物代謝能

  アクソルン サエンティエンチャイ, 池中 良徳, ネスタ サム, ウスマ ジャムナーク, 水川 葉月, 中山 翔太, 石塚 真由美 日本毒性学会学術年会 43 (0) P -237 2016年 [査読無し][通常論文]
   

  African hedgehog, <i>Atalerix albiventris</i>, is a spiny mammal which becomes famous exotic pet in many counties. In order to elucidate xenobiotic metabolisms ability of hedgehogs, pyrene, one of the typical polycyclic aromatic hydrocarbon were exposed. From in vivo exposure study, pyrene was biotransformed to glucuronide and sulfate conjugates such as pyrene-1-glucuronide, pyrene-1-sulfate, and pyrenediol-sulfate and excreted to urine. Pyrene-1-glucuronide was main metabolite and limited excretion of sulfate conjugates were observed. Based on the results of in vivo exposure study, in vitro enzymatic kinetic experiments were performed by using various substrate and compare to rat and pig. Enzyme efficiency of cytochrome P450 (CYP) mediated Ethoxyresorufin <i>O</i>-deethylase activity, and warfarin 4'-, 6-, and 8-hydroxylation activity in hedgehogs were lower than that of rats. Furthermore, UDP-glucuronosyltransferase activities in hedgehogs were also lower <i>Km</i> than that of rats. Interestingly, the enzymatic efficiency of sulfation in hedgehogs was significantly lower than that of rats, whereas hedgehogs had similar sulfation ability as in pigs. Sulfation of hedgehogs may be limit activity in xenobiotic metabolism.
• Constitutive Effects of Lead on Aryl Hydrocarbon Receptor Gene Battery and Protection by β-carotene and Ascorbic Acid in Human HepG2 Cells.

  Wageh S Darwish, Yoshinori Ikenaka, Shouta M M Nakayama, Hazuki Mizukawa, Mayumi Ishizuka Journal of food science 81 (1) T275-81 -T281 2016年01月 [査読無し][通常論文]
   

  Lead (Pb) is an environmental pollutant that can get entry into human body through contaminated foods, drinks, and inhaled air leading to severe biological consequences, and has been responsible for many deaths worldwide. The objectives of this study were 1st to investigate the modulatory effects of environmentally relevant concentrations of Pb on AhR gene battery, which is controlling xenobiotics metabolism. 2nd, trials to reduce Pb-induced adverse effects were done using some phytochemicals like β-carotene or ascorbic acid. Human hepatoma (HepG2) cell lines were exposed to a wide range of Pb concentrations varying from physiological to toxic levels (0 to 10 mg/L) for 24 h. High Pb concentrations (1 to 10 mg/L) significantly reduced phase I (CYP1A1 and 1A2) and phase II (UGT1A6 and NQO1) xenobiotic metabolizing enzyme mRNA expression in a mechanistic manner through the AhR regulation pathway. Additionally, these Pb concentrations induced oxidative stress in HepG2 cells in terms of production of reactive oxygen species (ROS) and induced heme oxygenase-1 mRNA expression in a concentration-dependent phenomenon. Coexposure of HepG2 cells to physiological concentrations of some micronutrients, like β-carotene (10 μM) or ascorbic acid (0.1 mM), along with Pb (1 mg/L) for 24 h significantly reduced the levels of ROS production and recovered AhR mRNA expression into the normal levels. Thus, consumption of foods rich in these micronutrients may help to reduce the adverse effects of lead in areas with high levels of pollution.
• 鳥類における新規腎障害マーカーの探索

  石井千尋, 池中良徳, 市居修, 中山翔太, 西村紳一郎, 大橋哲, 田中誠一, 齊藤慶輔, 渡邊有希子, 水川葉月, 石塚真由美 日本野生動物医学会大会・講演要旨集 22nd 123 2016年 [査読無し][通常論文]
  
• 鳥類におけるグルクロン酸抱合酵素による薬物代謝

  新屋惣, 池中良徳, 中山翔太, 石井千尋, 水川葉月, 齊藤慶輔, 渡邊有希子, 伊藤真輝, 高江洲昇, 石塚真由美 日本野生動物医学会大会・講演要旨集 22nd 97 2016年 [査読無し][通常論文]
  
• 本当にソノポレーションか?

  佐々木東, 工藤信樹, 中山翔太, 滝口満喜 日本超音波医学会光超音波画像研究会プログラム・抄録集 2016 (2nd) 22‐24 2016年 [査読無し][通常論文]
  
• In situ肝灌流モデルによる殺鼠剤抵抗性野生クマネズミにおけるワルファリン代謝能の解明

  武田一貴, 池中良徳, 田中和之, 中山翔太, 谷川力, 水川葉月, 石塚真由美 日本分子生物学会年会プログラム・要旨集(Web) 39th ROMBUNNO.3LBA‐070 (WEB ONLY) 2016年 [査読無し][通常論文]
  
• ポリ塩化ビフェニル（PCBs）のin vivo暴露によるネコの異物代謝解明と甲状腺ホルモンへの影響評価

  水川 葉月, 高口 倖暉, 田辺 信介, 石塚 真由美, 前原 美咲, 横山 望, 市居 修, 滝口 満喜, 野見山 桂, 西川 博之, 池中 良徳, 中山 翔太 日本毒性学会学術年会 43 (0) P -6 2016年 [査読無し][通常論文]
   

  ポリ塩化ビフェニル（PCBs）の水酸化代謝物であるOH-PCBsは、肝臓内で薬物代謝酵素より生成され、その後体外へ排泄される。しかしながら、一部の水酸化代謝物は甲状腺ホルモン（TH）と類似の構造をもつため、THの恒常性を撹乱することが危惧されている。これまでに、多様な陸棲哺乳類の血中OH-PCBsを分析したところ、種間でOH-PCBsの組成に差異が認められ、中でも、ネコのOH-PCBs残留パターンは他種と大きく異なることから、本種は特異な代謝機能を有することが示唆された。しかし、ネコの異物代謝能の研究は僅かであり、化学物質暴露による毒性影響も不明な点が多い。本研究では、ネコにおけるPCBs in vivo暴露試験を実施し、体内動態および代謝に関与する酵素活性や遺伝子を解析するとともに、化学物質の暴露評価に繋がる基盤的情報の収集を目的とした。
  コーン油に溶解した12異性体のPCBsを腹腔内投与し、経時採血した血清中PCBsおよびOH-PCBs濃度について同条件で実施したイヌのin vivo試験と比較した結果、異性体の残留パターンや体内動態にイヌとネコで種差が観察された。とくにネコでは低塩素化体の残留が顕著であった。また、代謝酵素活性および遺伝子解析の結果、PCBs暴露によりEROD、MROD、PROD活性は上昇するものの、第2相抱合酵素（UGTやSULT）活性は変化せず、PCBs暴露による抱合酵素活性への影響もみられなかった。また、CYP1A1およびCYP1A2遺伝子の発現量の上昇も認められた。
  本研究により、ネコのPCBs吸収・代謝・排泄能はイヌと異なることが示唆され、とくに低塩素化OH-PCBsの毒性リスクは高いことが予想された。低塩素化OH-PCBsは血中でTH輸送タンパクとの競合結合や、THの硫酸抱合排泄の阻害、TH起因性遺伝子の転写抑制などが報告されており、ネコの甲状腺機能障害が懸念される。
• 非実験動物における化学物質代謝能の特徴と種差

  池中良徳, 池中良徳, 筧麻友, 水川葉月, 中山翔太, 石塚真由美 日本薬学会年会要旨集(CD-ROM) 136th ROMBUNNO.S66-3 2016年 [査読無し][通常論文]
  
• Uridine Diphosphate-Glucuronosyltransferase (UGT) Xenobiotic Metabolizing Activity and Genetic Evolution in Pinniped Species

  Mayu Kakehi, Yoshinori Ikenaka, Shouta M. M. Nakayama, Yusuke K. Kawai, Kensuke P. Watanabe, Hazuki Mizukawa, Kei Nomiyama, Shinsuke Tanabe, Mayumi Ishizuka TOXICOLOGICAL SCIENCES 147 (2) 360 -369 2015年10月 [査読無し][通常論文]
   

  There are various interspecies differences in xenobiotic-metabolizing enzymes. It is known that cats show slow glucuronidation of drugs such as acetaminophen and strong side effects due to the UGT1A6 pseudogene. Recently, the UGT1A6 pseudogene was found in the Northern elephant seal and Otariidae was suggested to be UGT1A6-deficient. From the results of measurements of uridine diphosphate-glucuronosyltransferase (UGT) activity using liver microsomes, the Steller sea lion, Northern fur seal, and Caspian seal showed UGT activity toward 1-hydroxypyrene and acetaminophen as low as in cats, which was significantly lower than in rat and dog. Furthermore, UGT1A6 pseudogenes were found in Steller sea lion and Northern fur seal, and all Otariidae species were suggested to have the UGT1A6 pseudogene. The UGT1 family genes appear to have undergone birth-and-death evolution based on a phylogenetic and synteny analysis of the UGT1 family in mammals including Carnivora. UGT1A2-1A5 and UGT1A7-1A10 are paralogous genes to UGT1A1 and UGTA6, respectively, and their numbers were lower in cat, ferret and Pacific walrus than in human, rat, and dog. Felidae and Pinnipedia, which are less exposed to natural xenobiotics such as plant-derived toxins due to their carnivorous diet, have experienced fewer gene duplications of xenobiotic-metabolizing UGT genes, and even possess UGT1A6 pseudogenes. Artificial environmental pollutants and drugs conjugated by UGT are increasing dramatically, and their elimination to the environment can be of great consequence to cat and Pinnipedia species, whose low xenobiotic glucuronidation capacity makes them highly sensitive to these compounds.
• 抗血液凝固系殺鼠剤の標的分子であるビタミンKエポキシド還元酵素(VKOR)の鳥類における特徴及び種差

  森田鮎子, 池中良徳, 中山翔太, 石井千尋, 水川葉月, 渡邉研右, 齊藤慶輔, 渡邊有希子, 伊藤真輝, 高江洲昇, 石塚真由美 日本獣医学会学術集会講演要旨集 158th 433 2015年08月30日 [査読無し][通常論文]
  
• Accumulation of Heavy Metals and Metalloid in Foodstuffs from Agricultural Soils around Tarkwa Area in Ghana, and Associated Human Health Risks.

  Nesta Bortey-Sam, Shouta M M Nakayama, Osei Akoto, Yoshinori Ikenaka, Julius N Fobil, Elvis Baidoo, Hazuki Mizukawa, Mayumi Ishizuka International journal of environmental research and public health 12 (8) 8811 -27 2015年07月28日 [査読無し][通常論文]
   

  This study was carried out to assess the extent of heavy metals and metalloid accumulation from agricultural soils to foodstuffs (viz, M. esculenta (cassava) and Musa paradisiaca (plantain)) around thirteen neighboring communities within Tarkwa, Ghana; and to estimate the human health risk associated with consumption of these foodstuffs. Concentrations of As, Cd, Co, Cr, Cu, Ni, Pb, and Zn were measured with an inductively coupled plasma-mass spectrometer and mercury analysis was done using a mercury analyzer. From the results, 30% of cassava samples collected, contained higher concentrations of Pb when compared to Codex Alimentarius Commission standard values. Bioconcentration factor indicated that Ni had higher capacity of absorption into food crops from soil than the other heavy metals. For both children and adults, the target hazard quotient (THQ) of Pb in cassava in communities such as Techiman, Wangarakrom, Samahu, and Tebe (only children) were greater than 1, which is defined as an acceptable risk value. This indicated that residents could be exposed to significant health risks associated with cassava consumption.
• Mercury concentrations in primary feathers reflect pollutant exposure in discrete non-breeding grounds used by Short-tailed Shearwaters

  Yutaka Watanuki, Takashi Yamamoto, Ai Yamashita, Chihiro Ishii, Yoshinori Ikenaka, Shouta M. M. Nakayama, Mayumi Ishizuka, Yuya Suzuki, Yasuaki Niizuma, C. E. Meathrel, R. A. Phillips JOURNAL OF ORNITHOLOGY 156 (3) 847 -850 2015年07月 [査読無し][通常論文]
   

  We measured mercury concentrations ([Hg]) and nitrogen stable isotope ratios (delta N-15) in the primary feathers of Short-tailed Shearwaters (Puffinus tenuirostris) that were tracked year-round. The [Hg] were highest in 14 birds that used the Okhotsk and northern Japan Seas during the non-breeding period (2.5 +/- A 1.4 mu g/g), lowest in nine birds that used the eastern Bering Sea (0.8 +/- A 0.2 mu g/g), and intermediate in five birds that used both regions (1.0 +/- A 0.5 mu g/g), with no effects of delta N-15. The results illustrate that samples from seabirds can provide a useful means of monitoring pollution at a large spatial scale.
• 鳥類で起こっているケミカルハザードとそのメカニズム

  中山翔太, 水川葉月, 池中良徳, 石塚真由美 日本野生動物医学会大会・講演要旨集 21st 22 2015年07月01日 [査読無し][通常論文]
  
• 北海道沿岸にストランディングした鯨類の臓器における金属濃度の測定とその比較検討

  川田大紀, 松田純佳, 松石隆, 中山翔太, 石塚真由美, 浅川満彦, 能田淳 日本野生動物医学会大会・講演要旨集 21st 76 2015年07月01日 [査読無し][通常論文]
  
• 第II相抱合反応の種差:食肉目におけるグルクロン酸抱合酵素の進化と遺伝子構造

  池中良徳, 筧麻友, 中山翔太, 川合佑典, 渡邊研右, 水川葉月, 野見山桂, 田辺信介, 石塚真由美 環境化学討論会要旨集(CD-ROM) 24th ROMBUNNO.3A‐06 2015年06月17日 [査読無し][通常論文]
  
• 渡り性海鳥2種の越冬海域と羽の水銀濃度

  綿貫豊, 山下愛, 石塚真由美, 池中良徳, 中山翔太, 石井千尋, 山本誉士, 山本誉士, 伊藤元裕, 桑江朝比呂, 鈴木裕也, 新妻靖彰, MEATHREL C.E, TRATHAN P.N, PHILLIPS R.A 環境化学討論会要旨集(CD-ROM) 24th ROMBUNNO.P‐146 2015年06月17日 [査読無し][通常論文]
  
• タンチョウの水銀蓄積特性に関する検討

  寺岡宏樹, 岡本絵梨佳, 久道萌, 中山翔太, 池中良徳, 石塚真由美, 北澤多喜雄 環境化学討論会要旨集(CD-ROM) 24th ROMBUNNO.P‐145 2015年06月17日 [査読無し][通常論文]
  
• 野生齧歯類におけるワルファリン抵抗性獲得機序の解明

  武田一貴, 池中良徳, 田中和之, 中山翔太, 谷川力, 水川葉月, 石塚真由美 環境化学討論会要旨集(CD-ROM) 24th ROMBUNNO.3A‐07 2015年06月17日 [査読無し][通常論文]
  
• ウマにおけるシトクロムP450の特性評価:ジアゼパム代謝を担うCYP3Aの重要性

  水川葉月, 中山翔太, 池中良徳, 速水秋, DARWISH Wageh Sobhy, 渡邊研右, 川合佑典, 石塚真由美 環境化学討論会要旨集(CD-ROM) 24th ROMBUNNO.P‐030 2015年06月17日 [査読無し][通常論文]
  
• 猛禽類における鉛中毒問題と骨における鉛分布の解明

  石井千尋, 中山翔太, 池中良徳, 水川葉月, 中田北斗, 森田鮎子, 齊藤慶輔, 渡邊有希子, 神和夫, 田辺信介, 野見山桂, 林光武, 増田泰, 坂本健太郎, 石塚真由美 環境化学討論会要旨集(CD-ROM) 24th ROMBUNNO.3D‐05 2015年06月17日 [査読無し][通常論文]
  
• Phase II酵素の欠損動物と非欠損動物―新たな動物種マッピング―

  池中良徳, SAENGTIENCHAI Aksorn, SAENGTIENCHAI Aksorn, 筧麻友, DARWISH Wageh Sobhy, DARWISH Wageh Sobhy, 水川葉月, 中山翔太, 石塚真由美 Journal of Toxicological Sciences 40 (Supplement) S68 -3 2015年06月 [査読無し][通常論文]
   

  化学物質に対する最も基本的な生体防御機構は異物代謝系である。一方、これら異物代謝系の動物種差が、各動物の化学物質に対する感受性に強く寄与することが知られている。各生物が持つ異物代謝系には大きな種差があることが報告されている。例えば、異物代謝・第II相抱合反応において、ネコではグルクロン酸抱合、イヌではアセチル抱合およびブタでは硫酸抱合遺伝子が欠損していることが獣医学領域の研究から明らかになっており、投薬時に注意を要する。しかし、これら異物代謝系の動物種差に関する知見は、一部の実験動物を除くとほとんどの生物種で十分に解明されていない。<br>我々の研究グループでは、野生動物を含む様々な動物の異物代謝・第II相抱合反応を解明するため、in vivo、in vitroレベルおよびゲノム情報を用いた評価法の構築を行った。その結果、グルクロン酸抱合活性が低いと言われているネコ科動物以外にも、フェレットやトド、北オットセイ等の野生動物でもその活性が低いことが明らかになってきた。一方、硫酸抱合活性が低いと言われてきたブタでは、その活性は代表的な実験動物であるラットと変化が無いことが明らかになった。
• 日本海北部に来遊するキタオットセイの安定同位体比と利用海域との関係

  山田綾子, 堀本高矩, 石塚真由美, 池中良徳, 中山翔太, 水川葉月, 三谷曜子, 宮下和士 日本水産学会大会講演要旨集 2015 49 2015年03月27日 [査読無し][通常論文]
  
• Incidence and public health risk assessment of toxic metal residues (cadmium and lead) in Egyptian cattle and sheep meats

  W. S. Darwish, W. S. Darwish, M. A. Hussein, K. I. El-Desoky, Y. Ikenaka, S. Nakayama, H. Mizukawa, M. Ishizuka International Food Research Journal 22 (4) 1719 -1726 2015年01月01日 [査読無し][通常論文]
   

  Environmental pollution by heavy metals is a serious problem worldwide. This study aimed to investigate comparisons between concentrations of toxic metals (cadmium and lead) in the liver, kidneys, and muscle of Egyptian cattle and sheep. The effect of animal age on levels of toxic metal residues as well as results of a public health risk assessment is also reported. The results show that both cadmium and lead levels exceeded Food and Agriculture Organization and World Health Organization permissible limits in the liver and kidneys. These parts had higher concentrations of toxic metals compared with muscle in the two animal species examined. Age had a significant influence on toxic metal accumulation in both species. The hazard index indicates that consuming the livers and kidneys of these animals might pose a health risk.
• Protective effects of carotenoids and retinoids on benzo[a]pyrene induced mutagenicity and oxidative stress

  DARWISH Wageh Sobhy, IKENAKA Yoshinori, NAKAYAMA Shouta, MIZUKAWA Hazuki, ISHIZUKA Mayumi 日本毒性学会学術年会 42 (0) O -20 2015年 [査読無し][通常論文]
   

  Benzo[a]pyeren (B[a]P) is one of the polycyclic aromatic hydrocarbons which is formed due to smoking of foods, incomplete combustion of woods, vehicle exhausts and cigarettes smokes. B[a]P gets entry into human and animal bodies mainly through their diets. B[a]P is confirmed to be pro-mutagenic and pro-carcinogenic to animals and humans in many studies. <br>Carotenoids such asβ-carotene and its metabolites like retinol and retinoic acids have a confirmed antioxidant activities through their radical scavenging roles. <br>The aim of this study, was firstly to estimate the B[a]P levels in fresh and heat treated meats. Additionally, B[a]P induced mutagenicity was studied using Salmonella mutagenicity assay. Moreover, B[a]P induced oxidative stress was examined using human hepatoma cell line (HepG2) cells after exposure to the relevant concentrations of B[a]P formed in heat-treated foods. In addition, the protective effects of carotenoids and retinoids against these harmful effects were also examined. The mechanisms behind these effects were also investigated.<br>The obtained results confirmed that carotenoids and retinoids have clear protective effects against B[a]P induced mutagenicity and oxidative stress, probably through their ability of induction of phase II and III enzymes and interference with the induction of phase I enzymes.
• 外来化学物質の代謝の種差

  石塚真由美, 中山翔太, 水川葉月, 池中良徳 日本毒性病理学会講演要旨集 31st (JA)44,(EN)116 2015年 [査読無し][通常論文]
  
• ニワトリにおけるDDTの汚染状況と臓器蓄積性の解析

  伊藤玄悟, 池内良徳, BEYENE Yared, 中山翔太, 水川葉月, VUREN Johannes, WEPENER Victor, SMIT Nico, WYNAND Vlok, 石塚真由美 日本獣医学会学術集会講演要旨集 157th 533 2014年08月11日 [査読無し][通常論文]
  
• アフリカのゴミ集積場における化学物質の汚染実態と生体への健康影響の評価:ナイロビのダンドラ地域における家畜の重金属汚染の例

  中田北斗, 中山翔太, 水川葉月, 池中良徳, 石井千尋, YARED YB, YABE John, 今内覚, 石塚真由美 日本獣医学会学術集会講演要旨集 157th 533 2014年08月11日 [査読無し][通常論文]
  
• 日本における猛禽類の鉛中毒被害状況と中毒原因,鉛体内分布の解明

  石井千尋, 中山翔太, 池中良徳, 水川葉月, 中谷北斗, 齊藤慶輔, 渡邊有希子, 田辺信介, 野見山桂, 林光武, 増田泰, 坂本健太郎, 石塚真由美 日本獣医学会学術集会講演要旨集 157th 533 2014年08月11日 [査読無し][通常論文]
  
• ケニアの大規模ゴミ集積場・ダンドラ地域における家畜の化学物質汚染の実態と住民の健康影響評価

  中田北斗, 中山翔太, 水川葉月, 池中良徳, 石井千尋, YOHANNES Yared B, 今内覚, 石塚真由美 J Toxicol Sci 39 (Supplement) S336 -187 2014年07月 [査読無し][通常論文]
   

  ケニア共和国の首都ナイロビ市内の大規模ゴミ集積場・ダンドラ地域は、世界第二位の巨大・高密度スラム街であり、地域内の子供の半数はWHO基準（100 μg/kg）以上の血中Pb濃度であることが報告されているが、家畜の汚染や生体への曝露源に関する報告はない。本研究では、ダンドラおよび対照区として同国・ナクル地域に生息するヤギ、ヒツジ、ブタおよびウシの血中金属類（10元素）濃度およびPb安定同位体比をICP-MSにより、PCBsおよび有機塩素系農薬（OCPs）濃度をGC-MSとGC-ECDにより測定した。<br> その結果、全てのサンプルでCr, Mn, Ni, Cu, Zn, As, Mo, Agの高濃度蓄積は認められず、PCBsおよびOCPsは検出限界以下であった。Pb濃度はナクルに比べてダンドラで高い蓄積傾向を示し、ヤギおよびヒツジでは有意差が認められた。ブタの平均Pb濃度はダンドラ（2600 μg/kg, dry wt:dw）がナクル（73 μg/kg, dw）の約35倍の高値を示した。ダンドラのウシからは、ヘム合成に関与するアミノレブリン酸脱水酵素活性が低下するとされる値（100μg/kg）と同程度のPb濃度（91 μg/kg以上）が検出され、血液毒性等の中毒症状の蔓延が示唆された。Cd濃度の地域差および種差は認められなかったが、総じて高値（570±460 ng/kg, dw）を示し、ウシの摂食によるヒトのCd曝露が示唆された。Pb安定同位体比は地域および動物種により異なる傾向を示し、地域内に複数の曝露源があること、動物種により主要な曝露源が異なることが示唆された。<br> 本研究より、両地域に生息する家畜には高濃度のPb, Cdが蓄積し、特にPb汚染はダンドラで深刻なレベルであり、その曝露源が複数存在することが示唆された。家畜と生活環境を共にするヒトへの同様の汚染も強く示唆された。
• 日本に生息する猛禽類の鉛汚染状況と鉛安定同位体比を指標とした汚染源の解明

  石井千尋, 中山翔太, 池中良徳, 水川葉月, 中田北斗, 齊藤慶輔, 渡邊有希子, 田辺信介, 野見山桂, 林光武, 増田泰, 坂本健太郎, 石塚真由美 J Toxicol Sci 39 (Supplement) S336 -188 2014年07月 [査読無し][通常論文]
   

  【はじめに】北海道では、猛禽類において鉛弾摂取による鉛中毒が問題となっている。現在は鉛弾の使用規制が設けられているものの、未だに被害個体が発見されている。また、本州など他地域でも鉛中毒個体が発見されているが、北海道を除く地域における汚染実態調査は極僅かであり、鉛弾使用規制も不十分である。そこで、本研究では北海道、本州、四国において死亡した猛禽類の鉛濃度と鉛安定同位体比を測定し、鉛汚染状況と汚染源の解明を試みた。<br>【方法】試料は、1993年から2014年に北海道、本州、四国で死亡したイヌワシ、トビ、オオワシ、オオタカ、フクロウ、オジロワシ、オオハヤブサ、クマタカ、サシバ、ハイタカ、ツミ、チョウゲンボウの計49個体の肝臓を採取し、誘導結合プラズマ質量分析計で鉛濃度と鉛安定同位体比（²⁰⁷Pb/²⁰⁶Pb、²⁰⁸Pb/²⁰⁶Pb）を分析した。<br>【結果と考察】本研究の結果、1999‐2014年に北海道で死亡した4羽のオオワシにおいて、鉛中毒が疑われる値（11.0-29.5 mg/kg、湿重量）が検出された。北海道では2004年に大型獣の狩猟における鉛弾使用が禁止されているが、2013、2014年に採取されたオオワシにおいても高濃度の鉛蓄積が検出され、このうち1羽からはレントゲン撮影と剖検で胃内に鉛弾の破片が認められた。また岩手県で死亡したイヌワシからも高濃度の鉛蓄積（2.0 mg/kg）が認められた。さらに鉛安定同位体比を分析した結果、高濃度の鉛蓄積個体の鉛安定同位体比の値が同程度であった。このうち1羽から鉛弾が検出されたことを考慮すると、これらの高濃度蓄積個体の汚染源は鉛ライフル弾であると考えられた。<br> 上記の結果から、猛禽類の鉛弾摂取による中毒が未だに問題となっていることが明らかとなった。従って、北海道以外の地域における調査、また日本全国における鉛弾流通の完全禁止など規制強化の検討が必要であると考えられた。
• 鰭脚類を中心とした食肉目において異物代謝を担うグルクロン酸抱合酵素の特徴

  筧麻友, 中山翔太, 水川葉月, 池中良徳, 渡邊研右, 坂本健太郎, 和田昭彦, 服部薫, 田辺信介, 野見山桂, 石塚真由美 J Toxicol Sci 39 (Supplement) S281 2014年07月 [査読無し][通常論文]
  
• 鰭脚類におけるグルクロン酸抱合酵素の解析

  筧麻友, 池中良徳, 中山翔太, 水川葉月, 渡邊研右, 坂本健太郎, 和田昭彦, 服部薫, 田辺信介, 野見山桂, 石塚真由美 J Toxicol Sci 39 (Supplement) S223 -9 2014年07月 [査読無し][通常論文]
   

  【目的】グルクロン酸抱合酵素(UGT)は、異物代謝の第Ⅱ相抱合反応を担い、各動物の化学物質感受性決定に関与することが報告されている。食肉目ネコ亜目(<i>Feliformia</i>)では環境化学物質や薬物等の代謝に関与するUGT1A6の偽遺伝子化が報告されており、この偽遺伝子化によりアセトアミノフェン等の薬物の毒性作用が強く表れることが知られている。一方、食肉目に属する鰭脚類(<i>Pennipedia</i>)では、PCB、DDTなどの残留性有機汚染物質の高濃度蓄積が報告されているが、感受性に関与するUGTについての研究がほとんど行われていない。そこで、鰭脚類を中心とした食肉目において、UGTの機能解析及び系統解析を行い、種差を明らかにすることを目的とした。<br>【方法】食肉目に属するネコ(<i>Felis catus</i>)、イヌ(<i>Canis familiaris</i>)、鰭脚類であるトド(<i>Eumetopias jubatus</i>)、キタオットセイ(<i>Callorhinus ursinus</i>)、カスピカイアザラシ(<i>Phoca caspica</i>)及び対照としてラット(<i>Rattus norvegicus</i>)の肝臓ミクロソームを調整した。この肝臓ミクロソームを用いて、1-ヒドロキシピレンを基質としてUGT活性を測定した。さらに食肉目UGT1A遺伝子について、他の哺乳類と比較し、系統解析を行った。<br>【結果及び考察】1-ヒドロキシピレンを基質として用いたところ、イヌはラットと同程度のUGT活性を示したが、鰭脚類3種およびネコのUGT活性はラットの3分の1以下だった。また、UGT1A遺伝子は一般に2-10程度のホモログが近接して染色体上に存在しているが、系統解析及びシンテニー解析より、食肉目は齧歯目に比べUGT1A領域が短くUGT1A分子種数が少ないことが確認された。さらに、トドおよびキタオットセイでは、UGT1A6のエクソン1領域に2塩基挿入によるストップコドンが生じ、偽遺伝子化していることが明らかになった。以上の結果より、鰭脚類は、UGTによる異物代謝能が低く、環境化学物質に対する感受性が高い可能性が考えられた。
• ネコ科動物における有機ハロゲン化合物の代謝能解析

  水川葉月, 池中良徳, 野見山桂, 田辺信介, 宇根有美, 伊藤真輝, 高江洲昇, 長野靖子, 中山翔太, 石塚真由美 環境化学討論会要旨集(CD-ROM) 23rd ROMBUNNO.3B-14 2014年05月14日 [査読無し][通常論文]
  
• 日本に生息する猛禽類における鉛汚染状況の解析

  石井千尋, 池中良徳, 中山翔太, 水川葉月, 齊藤慶輔, 渡邊有希子, 田辺信介, 野見山桂, 林光武, 増田泰, 坂本健太郎, 石塚真由美 環境化学討論会要旨集(CD-ROM) 23rd ROMBUNNO.3D-03 2014年05月14日 [査読無し][通常論文]
  
• ベクターコントロールのための薬剤散布の生態系およびヒト健康に与える影響評価:アフリカにおけるDDT使用の現状と課題

  池中良徳, YOHANNES Yared Beyene, 中山翔太, 水川葉月, VAN VUREN Johannes J, WEPENER Victor, SMIT Nico J, WYNAND Vlok, 石塚真由美 環境化学討論会要旨集(CD-ROM) 23rd ROMBUNNO.2A-08 2014年05月14日 [査読無し][通常論文]
  
• アフリカのゴミ集積場における化学物質の汚染実態と生体への健康影響の評価:ナイロビのダンドラ地域における重金属汚染の例

  中田北斗, 中山翔太, 水川葉月, 池中良徳, 石井千尋, YOHANNES Yared B, 今内覚, 石塚真由美 環境化学討論会要旨集(CD-ROM) 23rd ROMBUNNO.3D-01 2014年05月14日 [査読無し][通常論文]
  
• 鰭脚類においてグルクロン酸抱合酵素が担う異物代謝

  筧麻友, 池中良徳, 中山翔太, 水川葉月, 渡邉研右, 坂本健太郎, 和田昭彦, 服部薫, 田辺信介, 野見山桂, 石塚真由美 日本野生動物医学会大会・講演要旨集 20th 75 2014年 [査読無し][通常論文]
  
• 食肉目におけるグルクロン酸抱合酵素の遺伝子解析

  筧麻友, 池中良徳, 中山翔太, 水川葉月, 渡邉研右, 坂本健太郎, 和田昭彦, 服部薫, 田辺信介, 野見山桂, 石塚真由美 日本分子生物学会年会プログラム・要旨集(Web) 37th 3P-0853 (WEB ONLY) 2014年 [査読無し][通常論文]
  
• ハシボソミズナギドリの羽根の化学マーカーによる海洋環境モニタリング

  綿貫豊, 山下愛, 保科賢司, 鈴木優也, 山本誉士, 石塚真由美, 池中良徳, 中山翔太, 石井千尋, 新妻靖章, MEATHREL C, PHILLIPS R. A 日本鳥学会大会講演要旨集 2013 53 2013年09月13日 [査読無し][通常論文]
  
• In vitroにおけるウマのジアゼパム代謝

  速水秋, DARWISH Wageh, 池中良徳, 中山翔太, 石塚真由美 日本獣医学会学術集会講演要旨集 156th 388 2013年08月30日 [査読無し][通常論文]
  
• Molecular evaluation of a new highly sensitive aryl hydrocarbon receptor in ostriches

  N. Fujisawa, W. S. Darwish, Y. Ikenaka, E. Kim, J. Lee, H. Iwata, S. Nakayama, M. Ishizuka POULTRY SCIENCE 92 (7) 1921 -1929 2013年07月 [査読無し][通常論文]
   

  A 1,000-fold difference has been reported in dioxin sensitivity between avian species. This difference is because the 2 amino acids in the type 1 aryl hydrocarbon receptor (AhR1), at positions 325 and 381, correspond to Leu324 and Ser380 in chickens. The chicken had been reported to be the only avian species to possess a sensitive form of AhR1. This is the first study to reveal that the ostrich (Struthio camelus), a nonchicken species, also has a pair of amino acids (Ile-325 and Ser-381) that show high ligand affinity. However, the alignment of the AhR1 cDNA sequence showed that the AhR sequence in the ostrich was different than that of other avian species even though the critical amino acids were observed at positions 325 and 381. Ostrich AhR1 was also evaluated in a heterologous expression study. Ostrich AhR1 showed very high transcriptional activity of the cytochrome P450 1A5 (CYP1A5) gene in African Green Monkey Cercopithecus aethiops kidney cells (COS-7) treated with Sudan III. In primary cultures of ostrich kidney cells, CYP1A5 expression was induced by Sudan III at a lower (or almost identical) concentration to that observed in the chicken. The present study revealed a new AhR ligand sensitive avian species (i.e., the ostrich).
• 鳥類における金属の汚染状況と蓄積特性の解析

  石井千尋, 池中良徳, 中山翔太, 鈴木優也, 綿貫豊, 渡邊雄児, 福若雅章, YOHANNES Yared B, 川合佑典, 石塚真由美 環境化学討論会要旨集(CD-ROM) 22nd ROMBUNNO.1-1B-1-1 2013年07月 [査読無し][通常論文]
  
• ガーナの金鉱山周辺(オブアシ自治区)におけるヒ素汚染と陸生哺乳類への毒性影響評価

  大谷豪, 池中良徳, 中山翔太, AKOTO Osei, APAU Joseph, BAIDOO Elvis, 石塚真由美 環境化学討論会要旨集(CD-ROM) 22nd ROMBUNNO.1-1B-2-2 2013年07月 [査読無し][通常論文]
  
• 野生げっ歯類におけるワルファリン抵抗性機構

  池中良徳, 田中和之, 中山翔太, 春成常仁, 谷川力, 水川葉月, 石塚真由美 環境化学討論会要旨集(CD-ROM) 22nd ROMBUNNO.3-2D-6-3 2013年07月 [査読無し][通常論文]
  
• オオミズナギドリの越冬海域と尾羽の水銀濃度

  綿貫豊, 山下愛, 石塚真由美, 池中良徳, 中山翔太, 石井千尋, 山本誉士, 伊藤元裕, 桑江朝比呂 日本生態学会大会講演要旨集 60th 118 2013年03月05日 [査読無し][通常論文]
  
• 海鳥における金属の汚染状況と蓄積特性の解析

  石井千尋, 池中良徳, 中山翔太, 鈴木優也, 綿貫豊, 渡邊雄児, 福若雅章, YARED Yohannes Beyene, 川合佑典, 石塚真由美 日本獣医学会学術集会講演要旨集 155th 260 2013年03月04日 [査読無し][通常論文]
  
• Pyrene metabolism and the role of phase I and phase II enzymes in freshwater turtles

  OROSZLANY Balazs, IKENAKA Yoshinori, SAENGTIENGCHAN Aksorn, OGURI Mami, NAKAYAMA Shouta, ISHIZUKA Mayumi 日本毒性学会学術年会 40 (0) 2013年 [査読無し][通常論文]
   

  Introduction : Reptile populations all around the world are decreasing. The dominant stressors are decrease of habitats, targeted harvesting and climate change. Environmental pollution could be a common factor weakening populations, yet we know little about the effect of xenobiotics on reptiles. Pyrene, as a representative of polycyclic aromatic hydrocarbons (PAHs), was choosen to study the metabolism in freshwater turtles, as disasters involving PAHs (oil spills) are one of the main causes of health and reproductive problems in water-living organism. <br>Materials and Methods:Red-eared sliders (<i>Trachemys scripta elegans</i>), Chinese pond turtles (<i>Mauremys reevesii</i>) and Chinese softshell turtles (<i>Pelodiscus sinensis</i>) were used. Pyrene exposure occurred thorugh oral feeding (4 mg/kg pyrene, dissolved in corn oil) or through water (250 &mu;g/l). Exposed water was filtered, passed through a solid-phase cartridge, and eluded with methanol. Metabolites were determined by HPLC with FD equipped with an ODS column, and identified by an MS/MS system. Liver subcellular fractions were isolated from fresh samples, protein concentration were measured by BCA protein assay. EROD, UGT and SULT activity were measured.<br>Results and Discussion:Distinct metabolite distributions were measured for each species. The dominant metabolite in all three species was pyrene-1-sulfate. All enzyme activities were low compared to mammals (rat). Sulfate conjugation was the dominant phase II metabolic pathway in all three species.
• Regulatory effects of carotenoids on Aryl hydrocarbon receptor (AhR) gene battery

  DARWISH Wageh Sobhy, IKENAKA Yoshinori, NAKAYAMA Shouta, ISHIZUKA Mayumi 日本毒性学会学術年会 40 (0) 2013年 [査読無し][通常論文]
   

  <b>[Introduction]</b> <br> In our previous work, positive correlations between CYP1A- dependent activities, protein expression and &beta;-carotene (BC) accumulation in the ungulates were observed, however these cross-talks were poorly understood. Additionally, the regulatory effects of carotenoids on xenobiotics metabolizing enzymes (XMEs) had received little attention. Thus, the aim of the current study is to deeply investigate the constitutive response of AhR gene battery to the exposure to BC under various doses in the human hepatoma cell line (HEPG2) cells. Moreover, the possible regulatory mechanisms of these cross-talks between AhR and BC will be declared.<br> <b>[Materials and Methods]</b> <br> HEPG2 cell lines were treated with different concentrations of BC (0-10 &micro;M) for 12-24h. The mRNA expression for phase I (CYP1A1 and 1A2), Phase II (UGT1A6 and NQO1) enzymes and AhR were examined using Real-Time PCR. Protein expression of AhR was investigated using western blotting. Rat H4IIE cells were transfected with h-XRE luciferase reporter plasmid and exposed to BC for 24h and dual- luciferase reporter assay was performed.<br> <b>[Results and Discussion]</b> <br> BC differentially modulated XMEs (Phase I and II enzymes) expression in dose-dependent fashion. In parallel, BC induced AhR mRNA, protein expression and luciferase activity. Thus, &beta;-carotene differentially modulated AhR gene battery.
• Effects of lead, cadmium and other metals in domestic animals near a lead-zinc mine in Kabwe, Zambia

  YABE John, NAKAYAMA Shouta M.M, IKENAKA Yoshinori, MUZANDU Kaampwe, CHOONGO Kennedy, ISHIZUKA Mayumi, UMEMURA Takashi 環境化学討論会要旨集(CD-ROM) 21st ROMBUNNO.1B-12 2012年07月10日 [査読無し][通常論文]
  
• Levels and Bioaccumulation of Organochlorine Pesticides in Fish Species from Lake Ziway, ETHIOPIA

  YARED B. Yohannes, IKENAKA Yoshinori, WATANABE Kensuke, SAENGTIENCHAI Aksorn, NAKAYAMA Shouta, ISHIZUKA Mayumi 環境化学討論会要旨集(CD-ROM) 21st ROMBUNNO.1B-06 2012年07月10日 [査読無し][通常論文]
  
• アカハライモリとアフリカツメガエルにおける異物代謝酵素の発現量の比較

  上田春樹, 中山翔太, 川合佑典, 田中(上野)寛子, 池中良徳, 石塚真由美 は虫両棲類学会報 2012 (1) 89 2012年03月31日 [査読無し][通常論文]
  
• ラットにおけるシトクロムP450の系統差

  西山義広, 池中良徳, 大野円実, 渡邊研右, 川合佑典, 中山翔太, 田中和之, 石塚真由美 日本獣医学会学術集会講演要旨集 152nd 335 2011年08月31日 [査読無し][通常論文]
  
• ラットの消化管における異物代謝酵素の比較

  糸谷悠美, 池中良徳, 大野円実, 中山翔太, SOBHY Wageh, 石塚真由美 日本獣医学会学術集会講演要旨集 152nd 335 2011年08月31日 [査読無し][通常論文]
  
• Effects of current malaria control in lake environment; The levels of Organochlorine pesticide and toxic metals in fish species from Lake Awassa, ETHIOPIA

  YARED Beyene, IKENAKA Yoshinori, WATANABE Kensuke, SAENGTIENCHAI Aksorn, NAKAYAMA Shouta, ISHIZUKA Mayumi 環境化学討論会要旨集(CD-ROM) 20th ROMBUNNO.2E-01 2011年07月01日 [査読無し][通常論文]
  
• Metal and metalloid levels and bio-accumulation characteristics in soil, sediment, land plants and hippopotami (Hippopotamus amphibius L) from the South Luangwa National Park, Zambia

  NAKAYAMA Shouta M.M, IKENAKA Yoshinori, MUZANDU Kaampwe, CHOONGO Kennedy, M’KANDAWIRE Ethel, YASUDA Jun, ISHIZUKA Mayumi 環境化学討論会要旨集(CD-ROM) 20th ROMBUNNO.P-215 2011年07月01日 [査読無し][通常論文]
  
• Uptake of lead, cadmium and other metals in the liver and kidneys of cattle near a lead-zinc mine in Kabwe, Zambia

  YABE John, NAKAYAMA Shouta M.M, IKENAKA Yoshinori, MUZANDU Kaampwe, ISHIZUKA Mayumi, UMEMURA Takashi 環境化学討論会要旨集(CD-ROM) 20th ROMBUNNO.3E-01 2011年07月01日 [査読無し][通常論文]
  
• Metal concentration and stable isotope ratio analysis (d13C and d15N) in water, sediment and fish from Lake Itezhi-tezhi, Zambia

  NAKAYAMA Shouta M.M, IKENAKA Yoshinori, MUZANDU Kaampwe, CHOONGO Kennedy, YABE John, MUROYA Taro, UMEMURA Takashi, ISHIZUKA Mayumi 環境化学討論会要旨集(CD-ROM) 20th ROMBUNNO.2E-09 2011年07月01日 [査読無し][通常論文]
  
• ガーナの金鉱山周辺(オブアシ自治区)における金属汚染と野生ラットにおける毒性影響評価

  大谷豪, 池中良徳, 中山翔太, AKOTO Osei, APAU Joseph, BAIDOO Elvis, 石塚真由美 環境化学討論会要旨集(CD-ROM) 20th ROMBUNNO.P-214 2011年07月01日 [査読無し][通常論文]
  
• ラットの消化管における異物代謝酵素の発現パターン

  糸谷悠美, 池中良徳, 大野円実, 中山翔太, WAGEH Sobhy, 石塚真由美 日本獣医学会学術集会講演要旨集 151st 271 2011年03月01日 [査読無し][通常論文]
  
• Rattus属における薬物代謝能とシトクロムP450の種差・系統差

  西山義広, 田中和之, 大野円実, 渡邊研右, 川合佑典, 中山翔太, 谷川力, 春成常仁, 池中良徳, 石塚真由美 日本獣医学会学術集会講演要旨集 151st 270 2011年03月01日 [査読無し][通常論文]
  
• Heavy metal contamination of soil and sediment in Zambia

  Ikenaka Yoshinori, Nakayama Shouta M. M, Muzandu Kaampwe, Choongo Kennedy, Teraoka Hiroki, Mizuno Naoharu, Ishizuka Mayumi African Journal of Environmental Science and Technology 4 (11) 729 -739 2010年11月 [査読無し][通常論文]
   

  Heavy metal pollution is one of the most important problems in Zambia and causes serious effects to humans and animals. The aim of the present study was to evaluate the spatial distribution of heavy metals in main areas of Zambia and understand the characteristics of the pollution in each area. River and lake sediments and soil samples were collected from a large area of Zambia and analyzed for ten heavy metals (Cr, Co, Ni, Cu, Zn, As, Cd, Pb, Sr and Hg). The results indicate that heavy metal pollution in Zambia has strong regional differences. Using cluster analysis, the patterns of heavy metal pollution were divided into three major clusters: (1) Kabwe, (2) Copperbelt and (3) Lusaka and other areas. Heavy metals in the Copperbelt area are transported to downstream areas by the Kafue River. Pollution was also detected in national parks, and Lake Itezhi-tezhi has been polluted with high concentrations of Cu, possibly from mining activities in the upper reaches of the river. However, areas geographically distant from mining beds had only moderate or low heavy metal concentrations, although the concentrations of Pb and Zn were highly correlated with the populations of each town. Our findings indicate that heavy metal pollution in Zambia is still increasing, due to human activities, especially mining.
• アフリカ諸国における重金属汚染の現状と野生動物への影響

  池中良徳, 中山翔太, 石塚真由美 北海道獣医師会雑誌 54 (10) 569 -575 2010年10月10日 [査読無し][通常論文]
  
• ザンビア共和国をモデルとした微量元素汚染:ウシにおける微量元素濃度とメタロチオネインおよびサイトカインmRNA発現量

  室谷太郎, 池中良徳, 中山翔太, YABE John, MUZANDU Kaampwe, CHOONGO Kennedy, 今内覚, 梅村孝司, 石塚真由美 日本獣医学会学術集会講演要旨集 150th 323 2010年09月01日 [査読無し][通常論文]
  
• 野生ネズミの微量金属汚染‐日本におけるバイオモニタリングとその生体影響

  OROSZLANY Balazs, 池中良徳, 谷川力, 春成常仁, 田中和之, 中山翔太, 石塚真由美 日本獣医学会学術集会講演要旨集 150th 323 2010年09月01日 [査読無し][通常論文]
  
• ザンビア共和国の鉱床活動による微量元素汚染の野生ラットへの影響

  濱田泰平, 池中良徳, 中山翔太, MUZANDU Kaampwe, CHOONGO Kennedy, 寺岡宏樹, 石塚真由美 日本獣医学会学術集会講演要旨集 150th 323 2010年09月01日 [査読無し][通常論文]
  
• Estimation of environmental toxic effects by using wild rats: a possible model for terrestrial heavy metal biomonitoring

  OROSZLANY Balazs, IKENAKA Yoshinori, TANIKAWA Tsutomu, HARUNARI Tsunehito, TANAKA Kazuyuki, NAKAYAMA Shouta, ISHIZUKA Mayumi 環境化学討論会講演要旨集 19th 802 -803 2010年06月20日 [査読無し][通常論文]
  
• ザンビア共和国における土壌の重金属汚染

  中山翔太, 池中良徳, MUZANDU Kaampwe, CHOONGO Kennedy, 濱田恭平, 室谷太郎, 寺岡宏樹, 水野直治, 石塚真由美 環境化学討論会講演要旨集 19th 314 -315 2010年06月20日 [査読無し][通常論文]
  
• ザンビア共和国をモデルとした重金属類汚染:家畜における重金属類濃度とバイオマーカーmRNA発現量

  室谷太郎, 中山翔太, 池中良徳, YABE John, MUZANDU Kaampwe, CHOONGO Kennedy, 今内覚, 梅村孝司, 石塚真由美 環境化学討論会講演要旨集 19th 816 -817 2010年06月20日 [査読無し][通常論文]
  
• 多環芳香族炭化水素類(PAHs)に対する両棲類の異物代謝機構の解明:両棲類で観察された第II相抱合反応の特徴と種差

  上田春樹, 中山翔太, 池中良徳, 石塚真由美 J Toxicol Sci 35 (Supplement) S196 -320 2010年05月 [査読無し][通常論文]
   

  【目的】2004年国際自然保護連合より，世界の両棲類種の約1/3が危機に晒されており，また，1980年代以降120種以上が絶滅した可能性があると発表された。その原因の一つに環境化学物質への曝露が考えられている。しかし，両棲類では化学物質の感受性を決定する異物代謝系でさえ十分に解明されていない。そこで，環境化学物質の一つとして多環芳香族炭化水素類（PAHs）に注目し，両棲類における代謝反応，特に第II相抱合反応を明らかにすることを試みた。<BR>【方法】PAHsのモデルとして，ピレン（4環のPAH）を用いた。両棲類はアカハライモリ（Cynops pyrrhogaster），アフリカツメガエル（Xenopus laevis）を用いた。さらに対照として，ピレンの代謝に対し知見が得られているメダカ（Oryzias latipes）に注目し，ピレンの曝露（24h，125ppb，24℃）を行った。固相抽出（PS@Liq; 昭和電工）を用いて排泄物を含む水中からピレン代謝物を精製し，HPLC/蛍光検出および質量分析によりその同定を行った。<BR>【結果と考察】ピレン代謝産物として，魚類のメダカではグルクロン酸抱合体（m/z 297）と硫酸抱合体（m/z 393）のみが検出され，前者が主産物であった。両棲類のアフリカツメガエルでは硫酸抱合体が主産物として検出され，グルクロン酸抱合体はほとんど検出されなかった。一方，同じ両棲類であるアカハライモリでは，硫酸抱合体，グルクロン酸抱合体がともに検出され，アフリカツメガエルとは異なるパターンを示した。さらに，本研究において，両棲類では，メダカでは検出されなかった代謝産物が数種類検出された。これらの未知の代謝産物をMSにより測定したところ，m/z 299，315，381など，既知の抱合体とは異なるm/zが観察された。本研究により，化学物質の解毒経路に重要な第II相抱合反応について，両棲類では魚類とは異なる代謝抱合能を示すこと，有尾類と無尾類で異なる代謝パターンを示す可能性が示唆された。
• ザンビア共和国における重金属汚染:野生ラットをモデルとした陸圏の汚染モニタリング

  濱田恭平, 中山翔太, 池中良徳, KAAMPWE Muzandu, KENNEDY Choongo, 水野直治, 寺岡宏樹, 石塚真由美 日本獣医学会学術集会講演要旨集 149th 308 2010年 [査読無し][通常論文]
  
• Sources and distributions of heavy metals in Zambia: Environmental monitoring of soil and sediment contamination by heavy metals in Zambia

  IKENAKA Yoshinori, NAKAYAMA Shouta M.M, MUZANDU Kaampwe, CHOONGO Kennedy, SAKAMOTO Kentaro Q, TERAOKA Hiroki, MIZUNO Naoharu, ISHIZUKA Mayumi 環境化学討論会講演要旨集 18th 134 -135 2009年06月09日 [査読無し][通常論文]
  
• アカハライモリにおけるシトクロムP450 1Aのcharacterization

  中山翔太, 石塚真由美, 田中(上野)寛子, 坂本健太郎, 藤田正一 は虫両棲類学会報 2008 (1) 41 -42 2008年03月31日 [査読無し][通常論文]
  
• 両生類,特に有尾類アカハライモリを中心としたCYP1Aのcharacterization

  中山翔太, 石塚真由美, 田中‐上野寛子, 坂本健太郎, 藤田正一 日本獣医学会学術集会講演要旨集 144th 192 2007年08月27日 [査読無し][通常論文]
  
• Mechanism and kinetics of smectite dissolution under alkaline conditions

  T Sato, M Kuroda, S Yokoyama, K Fukushi, T Tanaka, S Nakayama GEOCHIMICA ET COSMOCHIMICA ACTA 67 (18) A415 -A415 2003年09月 [査読無し][通常論文]
  

受賞

• 2018年07月 日本毒性学会 第45回 日本毒性学会学術年会 優秀研究発表賞
   ザンビア共和国カブウェ鉱床地域における鉛汚染問題：10年間の研究結果と今後の課題 

  受賞者: 中山翔太
• 2012年03月 日本学術振興会 第２回（平成23年度）日本学術振興会育志賞
   アフリカの野生生物における環境汚染物質の毒性影響評価 

  受賞者: 中山翔太
• 2011年07月 日本環境化学会 第20回環境化学討論会 優秀学生賞
   Metal concentration and stable isotope ratio analysis (d13C and d15N) in water, sediment and fish from Lake Itezhi-tezhi, Zambia 

  受賞者: 中山翔太

共同研究・競争的資金等の研究課題

• アフリカの環境汚染によるヒトと動物の毒性学的影響とそのメカニズム解析

  日本学術振興会：科学研究費助成事業 国際共同研究加速基金(国際共同研究強化(B))

  研究期間 : 2022年10月 -2026年03月 

  代表者 : 石塚 真由美, 武田 一貴, 池中 良徳, 江口 哲史, 中山 翔太
• 外来性の化学物質（xenobiotics）に対する哺乳類の適応進化/変化

  日本学術振興会：科学研究費助成事業 基盤研究(A)

  研究期間 : 2021年04月 -2026年03月 

  代表者 : 石塚 真由美, 武田 一貴, 川合 佑典, 山崎 淳平, 池中 良徳, 中山 翔太, 早川 卓志

   

  我々はこれまでの研究により、高次の動物が外来性の化学物質（Xenobiotics）への「適応」ために、化学物質の代謝や排泄など、解毒のカスケードに沿って薬物代謝酵素などの一連の多様性を発展させてきたとの仮説を立てた。化学物質感受性には多様性があり、解毒代謝酵素の解析から、この多様性獲得の主要因は食餌由来の化学物質である可能性を報告した。本研究では食性の観点および重度環境汚染域に棲息する動物を中心に、哺乳類が日常的に曝露される化学物質にどのように適応してきたのか、多様な種を用いてその進化を機能面から明らかにする。これまでの研究で構築してきた多様な動物試料を用いた研究体制を生かし、食性のユニークな動物種を対象としたウェットな実験や、データベースを用いた網羅的解析により、外来性の化学物質に対する動物の「適応」と「共存」メカニズムを明らかにする。
  今年度は、食肉目クマ科、スカベンジャー種（腐肉食類）等について、ゲノムデータベースを用いた遺伝子解析を行った。外来化学物質の代謝を担う第I相反応酵素シトクロムP450、第II相反応のグルクロン酸転移酵素や硫酸転移酵素について、種間比較を行い、食性との関連性について解析した。特に硫酸転移酵素についてはこれまで分子進化と食性に関するデータは少なく、研究成果については、現在論文を作成している。野生げっ歯類、トカゲ、一部の食肉性哺乳類について、次世代シークエンサーを用いて、エクソーム解析およびトランスクリプトームを行っている。また農薬や重金属の環境汚染地域に生活・棲息している野生げっ歯類及びヒトについてメタボローム解析を行った。現在データを解析中であるが、野生げっ歯類についてはDDT高濃度汚染域に棲息している野生げっ歯類のステロイド代謝への影響が認められた。現在、野生げっ歯類をDDT環境汚染レベル下で世代飼育し、フィールドデータの検証を行っている。
• 毒性試験の高感度化・効率化を目指したMITAシステムの構築と実践

  日本学術振興会：科学研究費助成事業 挑戦的研究(開拓)

  研究期間 : 2022年06月 -2025年03月 

  代表者 : 池中 良徳, 野見山 桂, 新間 秀一, 杉尾 翔太, 石塚 真由美, 江口 哲史, 中山 翔太, 星 信彦, 平野 哲史
• 高精度XAFSを多階層陸生生物群に応用した遺伝子変異に依らない新規金属耐性機構

  日本学術振興会：科学研究費助成事業 挑戦的研究(開拓)

  研究期間 : 2020年07月 -2023年03月 

  代表者 : 中山 翔太, 藤森 崇, 中田 北斗

   

  野生ラットの臓器および内容物の鉛化学形態分布について、Pb L3端 XANESスペクトルによる解析を進めた。高濃度の鉛で汚染されたラットであることに加えて、凍結乾燥による試料均一性の増大や鉛濃度の濃縮によって、これまで鉛低濃度により測定が制約されていた生物試料のXANESスペクトルの臓器別、内容物別の測定に成功した。野生ラット3個体を主として、臓器は心臓、脳、肺、脾臓、肝臓、腎臓、筋肉など、胃・小腸・大腸の内容物、および糞便に対して、スペクトルの質を考慮したうえで系統的な解析を試みた。鉛化学形態の参照用XANESとして、グルタチオンと鉛の結合体や経口曝露源と考えられる現地の鉛汚染土壌等のデータを用いた。スペクトル形状および参照スペクトルとの線形結合フィッティングの結果、臓器別の鉛形態の違いや、消化器系や体内へ吸収された際の鉛化学形態の変化に関する知見を得ることができた。トカゲ亜目(Trachylepis wahlbergii)計112匹の臓器（肝臓、肺、卵巣/精巣）、血液、胃内容物を採集し肝臓中の金属濃度の測定を行った。土壌、トカゲ臓器、生体内で鉛と結合することが知られているグルタチオンなどと鉛の結合試料のPb L3端 XANESスペクトルによる解析を行った。鉛の周囲にグルタチオンをはじめ硫黄化合物が存在することが示唆された。このため、硫黄K端のエネルギー領域も計測し、個体間及び臓器間で異なるスペクトルパターンを得た。化学形態に加えて多角的なデータの取得を目的に遺伝子解析も実施しデータベース上にない全ゲノム配列データを得た。肝臓、肺、卵巣ついてRNA-seqも実施した。関係省庁・現地獣医師の協力の下、ニワトリ（10個体）、イヌ（26個体）の死亡個体の肝臓、腎臓、骨、腸管、脳、心臓、脾臓を採材し、鉛など10元素の濃度測定も行った。ラットの動物実験による確認実験も実施している。
• アフリカにおける新興・再興の環境汚染のフィールドベースの毒性メカニズム解析

  日本学術振興会：科学研究費助成事業 国際共同研究加速基金(国際共同研究強化(B))

  研究期間 : 2018年10月 -2022年03月 

  代表者 : 石塚 真由美, 池中 良徳, 中山 翔太, 中田 北斗

   

  近年、アフリカ諸国では急速な資源開発がすすめられている。そのため急激な環境の汚染が顕在化しており、一部の国では生態 系や家畜・ヒトにおける健康被 害が報告されるようになった。化学物質は、食糧生産や感染症制圧には必要不可欠であるが、途上国では化学物質汚染によるリスクを度外視して使用している現 状がある。2018年度に発表された大気汚染度を国別で分析した データでは世界ワースト10のうち7か国はアフリカで占められている。化学物質による脅威（ケミ カルハザード）については、 目に見えにくい潜在的な性質のため、対策が後手に回される傾向が強い。本研究では、アフリカでもっとも問題となっている金属、農薬についてその現状を明ら かにすること、およびフィールドトキシコ ロジーの概念により、そのメカニズムと現象を結 びつけることを目的としてい る。当該研究では、ザンビア大学（金属）および南アフリカのノースウェスト大学（再興農薬）、ガーナのクワメエンクルマ科学技術大学（KNUST 、新興農薬）と共 同研究を計画した。
  ザンビアでは鉛による環境汚染がヒトおよび動物に及ぼす毒性学的影響について調査を行った。特に、イヌを歩哨動物とした汚染モニタリング方法について報告した。また、乳児における鉛汚染の状況について調査を行った。ガーナではヒト試料の最終に向けた準備を行うとともに、ネオニコチノイドが神経系や脂肪代謝等に及ぼす影響について動物を用いた実験を行った。南アフリカではDDTが引き起こす毒性学的影響について、家畜や野生動物を用いてオミクス解析を行い、バイオマーカーの探索を行った。
• mlAOPコンセプトによる化学物質感受性多様性評価と殺虫剤中毒解明に向けた応用

  日本学術振興会：科学研究費助成事業 基盤研究(A)

  研究期間 : 2018年04月 -2022年03月 

  代表者 : 池中 良徳, 星 信彦, 川合 佑典, 石塚 真由美, 小林 篤史, 久保田 彰, 水川 葉月, 有薗 幸司, 平野 哲史, 加藤 恵介, 宮原 裕一, 市川 剛, 岡松 優子, 中山 翔太

   

  本年度は昨年度に引き続き、研究実施計画通り、以下の項目について、実施した。 ・mlAOPの基礎データ取得に向けた、げっ歯類およびゼブラフィッシュを用いた各種行動試験の実施：個体レベルでの評価として、様々な系統及び種の動物でオープンフィールドテストや高架式十字迷路等の行動試験を実施した。特に、マウスでは、神経毒性試験の新たな評価法として、２光子顕微鏡を用いた実験および解析を導入し、in vivoにおける化学物質の脳神経系への影響の可視化にチャレンジした。 ・組織レベルでの評価のための、イメージング解析を実施：組織レベルでの評価として、昨年度に引き続き、特にイメージング技術を駆使して実施した。特に超高分解能質量顕微鏡（MALDI-FT-ICR-MS 型;Bruker Solarix XR）によるネオニコチノイドおよびその代謝産物の組織分布のイメージング解析を試みた。カテコールアミンに着目した解析では、DPPによる誘導体化により、ドパミンの検出に成功した。一方、現在は再現性の評価や他のニューロトランスミッターへの応用を検討している。 ・細胞・分子レベルでの評価：昨年度に引き続き、SH-SY5Y細胞をモデル神経細胞として用い、細胞増殖パラメーターなどの各種項目についてデータを取得した。また、マイクロアレイを実施し、投与により変動する遺伝子群を明らかにした。また、標的分子のリン酸化状態についても解析を実施した。 ・ヒト尿試料を用いたバイオモニタリング：昨年度に引き続き、ボランティアを募り、一般市民延べ約1000人から尿試料の採取を実施し、尿中のネオニコチノイド濃度を測定した。また、有機野菜を食べてもらう事による尿中ネオニコチノイド低減効果についても明らかにした。
• 腸内細菌を軸とした金属汚染の新規影響評価法の開発～ザンビア鉛汚染地域をモデルに～

  日本学術振興会：令和2年度 (2020年度) 二国間交流事業 オープンパートナーシップ共同研究

  研究期間 : 2020年04月 -2022年03月 

  代表者 : 石塚真由美, 池中良徳, 中田北斗
• 希少鳥類の鉛汚染影響把握に必要な基盤技術開発

  環境再生保全機構：環境研究総合推進費・委託費【戦略的研究１】【戦略的研究２】

  研究期間 : 2018年04月 -2021年03月 

  代表者 : 石塚 真由美
• 小笠原諸島における殺鼠剤散布が野生動物に及ぼす影響の解明

  環境再生保全機構：平成30年度環境研究総合推進費（革新型研究開発（若手枠））

  研究期間 : 2018年04月 -2021年03月 

  代表者 : 中山翔太
• ザンビアにおける鉛汚染のメカニズムの解明と健康・経済リスク評価手法および予防・修復技術の開発

  JST/JICA：地球規模課題対応国際科学技術協力プログラム環境・エネルギー研究分野 「地球規模の環境課題の解決に資する研究」

  研究期間 : 2016年04月 -2021年03月 

  代表者 : 石塚真由美
• 「カクテル型」コンセプトによる「猛禽類対応型」新世代殺鼠剤の開発

  日本学術振興会：科学研究費助成事業 挑戦的研究(萌芽)

  研究期間 : 2018年06月 -2020年03月 

  代表者 : 石塚 真由美, 池中 良徳, 中山 翔太

   

  現在、殺鼠剤による猛禽類への二次被害が頻発している。このため、殺鼠剤抵抗性ラットに有効かつ安全な駆除方策は存在しない。これは抵抗獲得機序に対する研究の不足と野生動物における感受性評価法の欠如が原因である。本研究では、殺鼠剤抵抗性の獲得の原因を明らかにし、殺鼠剤の開発や非対象生物種への保全に資するデータを得ることを目的とした。本研究により、野生齧歯類の殺鼠剤への抵抗性の原因として、ビタミンKエポキシド還元酵素の結合ポケット内外の変異が抵抗性獲得に寄与する事を実証した他、NADPH産生の向上とそれに伴うシトクロムP450による殺鼠剤代謝能の活性化という新しい抵抗性獲得機序が明らかとなった。
• 高次の動物種における化学物質感受性の種差と適応進化の解明

  日本学術振興会：科学研究費助成事業 基盤研究(A)

  研究期間 : 2016年04月 -2020年03月 

  代表者 : 石塚 真由美, 池中 良徳, 中山 翔太, 水川 葉月

   

  哺乳類および鳥類について、肝臓における異物代謝の主要経路となるシトクロムP450（P450)、グルクロン酸転移酵素（UGT)、硫酸転移酵素（ST)についてクローニングを行い、その酵素学的特徴を明らかにした。UGTやSTが欠損もしくは極めて活性が低い動物種とその原因を明らかにした。また、現在、世界的に外来性の小型哺乳類の駆除には主に抗血液凝固系の殺鼠剤が使用されている。そこで、広範の動物種についての殺鼠剤感受性評価を行い、P450、UGTによる代謝能について、その種差を明らかにした。
• 低濃度・長期慢性暴露における鉛の毒性発現に腸内細菌叢が関係するか？

  日本学術振興会：科学研究費助成事業 国際共同研究加速基金(国際共同研究強化)

  研究期間 : 2018年 -2020年 

  代表者 : 中山 翔太

   

  本研究では、低濃度・中濃度・高濃度の鉛濃度が検出された子供を対象に、血中・尿中・糞便中の鉛濃度の推移および糞便を用いた腸内細菌叢解析を行い、鉛暴露が腸内細菌叢に及ぼす影響を解明する。 本事業中にザンビアに5回渡航しカウンターパートのJohn Yabe講師とディスカッションおよびサンプリングを実施した。現地で必要となるゲノム抽出装置、PCR装置などのラボのセッティングは初年度前半の渡航で完了した。約800名の子供から血液、尿、および糞便を収集した。現地クリニックにおけるオンサイト血液中鉛濃度測定を終了し、低濃度から高濃度の広範囲における血中鉛濃度を示す検体を集めた。糞便由来の腸内細菌叢解析を実施するためザンビア大学獣医学部に設置したラボにおいて細菌ゲノムを抽出した。これらの試料を対象に金属濃度および細菌叢解析を実施し、大規模なデータ取得が完了した。現在、これらのビッグデータを解析している段階である。対象を人だけでなく、人と生活圏を共有する野生ラットにも拡大し、血液、各種臓器、胃内容物、糞便を採取し、人では不可能な臓器中の金属濃度と細菌叢との関連を明らかにする。 共同研究の重要な目的である途上国における環境学・毒性学の研究者育成のためにザンビア大学より研究者を招聘し技術移転を実施した。招聘者はザンビア大学の学生に教育・指導を実施しており、当該分野の推進に貢献している。 2019年度より治療プロジェクトを遂行する世界銀行(World Bank)の担当者と実施計画のディスカッションを実施した。本共同研究のカウンターパートであるJohn YabeはWorld Bankプロジェクトにおけるメンバーでもあり、当該研究との連携の役割を担うことを確認した。
• 野生動物iHep細胞の作成とトッププレデターのMetabolism評価法の開発

  日本学術振興会：科学研究費助成事業 挑戦的研究(萌芽)

  研究期間 : 2017年06月 -2019年03月 

  代表者 : 池中 良徳, 川合 佑典, 鈴木 淳史, 三谷 曜子, 石塚 真由美, 水川 葉月, 中山 翔太

   

  本研究では、化学物質感受性のキーであるMetabolismの評価法を開発し、希少野生動物の感受性を明らかにする事である。この評価のためには、新鮮肝が必要であるが、希少種ではその入手が困難である。そこで、皮膚線維芽細胞からダイレクトリプログラミングにより肝臓様（iHep）細胞への誘導を試みた。先ずiHep作成に先立ち、本研究では数種のトッププレデターの線維芽細胞を入手し、その培養に成功した。培養した線維芽細胞を用い、iHep細胞への誘導を試みた結果、特定の因子を導入する事でアルブミンを発現する上皮細胞に変化する事を見出した。本研究を通じて、初めて野生動物iHep細胞の作成に成功した可能性が高い。
• 亜急性・慢性ネオニコチノイド中毒の診断法の開発と病態発生機序の解明

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2015年04月 -2019年03月 

  代表者 : 平 久美子, 池中 良徳, 中山 翔太, 小森 万希子, 藤岡 一俊, 川上 智規, 有薗 幸司

   

  ウサギにネオニコチノイド7種を投与し12-48時間後の尿を採取し、LC-TOF/MSと代謝物のスクリーニングソフトMetabolite Pilotを用い網羅的解析を行い、主要代謝物を見出し市販されてないものについて構造解析と有機合成を行った。 LC-ESI/MS/MSを用いた高感度分析法により親化合物7種、内部標準物質7種 に加え代謝産物20種の定量が、尿など液体試料と、組織や全血などマトリクスの多い試料で可能となった。 この方法を用い、フィールドレベルで随時尿を収集し分析したところ、親化合物とともに、脱メチルアセタミ プリド、脱メチルニテンピラム、水酸化イミダクロプリドが定量検出された。
• 次世代型殺鼠剤開発を目的とした殺鼠剤抵抗性ラットの抵抗性獲得機序の解明

  日本学術振興会：科学研究費助成事業 挑戦的萌芽研究

  研究期間 : 2016年04月 -2018年03月 

  代表者 : 石塚 真由美, 池中 良徳, 中山 翔太, 水川 葉月

   

  野生齧歯類は様々な感染症を媒介するため駆除する必要がある。駆除には殺鼠剤が用いられたがこれらに抵抗性を有す個体群が出現し駆除を困難にしている。従来抵抗性群は殺鼠剤の標的分子が変異し殺鼠剤が結合しにくい形になるのが原因と考えられてきた。本研究では殺鼠剤の解毒代謝機能を評価した。その結果、抵抗性群では肝で殺鼠剤を代謝し排泄する能力が向上しており、標的分子の変異と代謝能の向上という二つの機構を併せ持つことが判明した。
• 統合的メタロミクスによる鉛汚染源推定に有用な家畜・家禽の探索と種差の分子基盤解明

  日本学術振興会：科学研究費助成事業 若手研究(B)

  研究期間 : 2016年04月 -2018年03月 

  代表者 : 中山 翔太, 石塚 真由美, 池中 良徳, 水川 葉月, 平田 岳史

   

  年間23万人が主に鉱床由来の鉛中毒により死亡し、60万人以上の子供の知的発達に影響を及ぼしているが、汚染源推定に有用な手法は確立されていない。本研究では鉛汚染源推定に有用な家畜・家禽種を解明することを目的とした。高精度鉛同位体比解析より、アフリカを含めた発展途上国で流通し、またヒトの食糧源としても用いられるヤギやニワトリを用いることで、鉛汚染源の推定が可能であることを明らかにした。LA-ICP-MS（レーザー照射型 誘導結合プラズマ質量分析法）により、マウスにおける鉛の臓器内局所分布を解析した。脳の海馬領域の高濃度蓄積や、特に、腎臓の髄質において皮質よりも高濃度の鉛蓄積が確認された。
• ベクターコントロールが及ぼす希少野生動物への影響評価と新規感受性評価法の開発

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2015年04月 -2018年03月 

  代表者 : 池中 良徳, 石塚 真由美, 水川 葉月, 中山 翔太

   

  本研究では、アフリカのベクターコントロール地域である南アフリカのKwaZulu-Natal州に注目し、その汚染状況の調査および生息する生物に対する毒性影響評価を実施した。 家禽に着目した調査の結果、肝臓中DDT濃度は中央値として920 ng/g ww、最大濃度で14,400 ng/g wwと非常に高い値を示した。リアルタイムRT-PCR法により遺伝子発現解析を実施した結果、脂質代謝や合成や性ステロイドホルモン合成に関与する遺伝子群に影響を与えている事が明らかになった。本研究結果は、DDTが生体に一定の影響を与えている事を示しており、今後より適切なベクターコントロールを実施する必要性を示唆する。
• ネコにおける有機ハロゲン化合物の代謝機構解明と甲状腺機能の影響評価

  日本学術振興会：科学研究費助成事業 若手研究(B)

  研究期間 : 2015年04月 -2018年03月 

  代表者 : 水川 葉月, 石塚 真由美, 池中 良徳, 中山 翔太, 滝口 満善, 野見山 桂

   

  ネコにおけるPCBs短期投与試験およびBDE209長期投与試験を実施し、ネコにおける有機ハロゲン化合物の生体内動態（吸収、分布、代謝、排泄）の解明、甲状腺機能への影響評価、遺伝子解析やオミクス解析による毒性発現メカニズムの解明を目的とし、調査・研究を実施した。その結果、PCBsおよびBDE209曝露によって、甲状腺機能への影響のみならず酸化ストレスの増大やNADPHの生産の撹乱、脂質代謝機能や免疫機能のかく乱なども予想された。
• ケミカルハザード問題の克服に向けた国際コミッション

  日本学術振興会：研究拠点形成事業（アジア・アフリカ型）

  研究期間 : 2015年04月 -2018年03月 

  代表者 : 石塚真由美
• ザンビアのヒト・家畜における毒性金属汚染の解明と家畜の金属汚染低減技術の開発

  日本学術振興会：二国間交流事業共同研究

  研究期間 : 2015年06月 -2017年06月 

  代表者 : 中山翔太
• 生体外異物代謝におけるグルクロン酸抱合の進化と細胞内デリバリーに対する機能解明

  日本学術振興会：科学研究費助成事業 挑戦的萌芽研究

  研究期間 : 2015年04月 -2017年03月 

  代表者 : 池中 良徳, 水川 葉月, 中山 翔太

   

  当該研究では、比較生物学・系統解析により、脊椎動物におけるグルクロン酸抱合酵素(UGT)の種差を明らかにする事で、その生体内での役割と分子メカニズムについて解明することを試みた。その結果、UGT1A6活性が低いと報告されていたネコ以外にも、鰭脚類で極めてその活性が低い事が明らかになった。更に、ネコやアザラシではUGT1Aに加えUGT2B活性が低く、偽遺伝子化している事が示唆された。この結果から、グルクロン酸抱合は哺乳動物にとって極めて重要な解毒反応であると共に、欠損している動物では化学物質にとってのハイリスクアニマルであることが示唆された。
• ベクターコントロールのための薬剤散布の生態系およびヒト健康に与える影響評価

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2014年04月 -2017年03月 

  代表者 : 池中 良徳, 石塚 真由美, 中山 翔太, 水川 葉月, 櫻井 達也, 宮原 裕一, 下鶴 倫人, 中山 翔太, 水川 葉月

   

  WHOはハマダラカの駆除のためDDTの使用を推進しており、アフリカ等の途上国を中心に、室内残留散布として使用されている。一方、DDTは難分解性で環境中の長期間残留が知られ、発がんや内分泌撹乱などの生体影響も疑われている。当該研究では、南アフリカ共和国・クワズルナタール州をベクターコントロールモデル地域とし、DDT・IRSの潜在的な毒性リスク評価を行った。 ニワトリ、ラット、野生鳥類の卵のを採取し、その分析を行った結果、いずれの試料からも極めて高濃度のDDT蓄積が観察された。本研究結果は、環境負荷が小さいとされるDDT・IRSにおける、潜在的な毒性影響および環境リスクの存在を示唆していた。
• アフリカにおける鉛汚染問題解決に向けた共同研究および汚染対策に関するシンポジウムの実施

  北海道大学：平成27年度大学間協定校交流事業

  研究期間 : 2015年04月 -2016年03月 

  代表者 : 中山翔太
• 鉛汚染源推定に有用な家畜・家禽種の探索～鉛安定同位体の生体内分別崩壊における閾値の動物種差を指標に～

  ニッセイ財団：平成27年度 若手研究・奨励研究助成

  研究期間 : 2015年04月 -2016年03月 

  代表者 : 中山翔太
• ペットのネコにおける有機ハロゲン代謝物の分析法開発と代謝機構解明およびリスク評価

  日本学術振興会：科学研究費助成事業 研究活動スタート支援

  研究期間 : 2013年08月 -2015年03月 

  代表者 : 水川 葉月, 石塚 真由美, 池中 良徳, 中山 翔太, 滝口 満善, 野見山 桂

   

  ペットのネコに着目し、研究報告例の少ない液体クロマトグラフタンデム質量分析計（LC-MS/MS）を用いた有機ハロゲン化合物であるポリ塩化ビフェニル（PCBs）およびポリ臭素化ジフェニルエーテル（PBDEs）の代謝物の分析法を開発した。さらに、第I相、第II相代謝活性を測定しネコにおける有機ハロゲン化合物に対する代謝能評価を試みた。
• アフリカにおける有害金属汚染問題の解決のための共同研究実施と国際環境毒性シンポジウムの開催

  北海道大学：平成26年度大学間協定校交流事業

  研究期間 : 2014年04月 -2015年03月 

  代表者 : 中山翔太
• 北海道を中心に生息する野生鳥類の金属汚染解明と分子生物学的解析による生体影響評価

  秋山記念生命科学振興財団：2013年度研究助成（奨励）

  研究期間 : 2013年04月 -2014年03月 

  代表者 : 中山翔太
• アフリカ汚染地域をモデルとした化学物質汚染に弱い野生動物・食肉用動物種の解明～環境毒性学アプローチからの生態系保全・食糧確保問題への取り組み～

  三井物産：三井物産環境基金

  研究期間 : 2012年04月 -2014年03月 

  代表者 : 中山翔太
• ザンビア共和国で進行する重金属汚染のヒト・野生動物への影響評価およびザンビア大学、ザンビアの政府関係機関と連携した環境政策の実施

  損保ジャパン環境財団：2011年度 学術研究助成金

  研究期間 : 2011年04月 -2012年03月 

  代表者 : 中山翔太
• アフリカの野生動物における環境汚染物質の毒性影響評価

  日本学術振興会：特別研究員奨励費(DC2)

  研究期間 : 2010年04月 -2012年03月 

  代表者 : 中山翔太
• アフリカの野生動物における環境汚染物質に高感受性を示すハイリスク動物種の解明

  日本学術振興会：科学研究費助成事業 特別研究員奨励費

  研究期間 : 2012年 -2012年 

  代表者 : 中山 翔太

   

  近年の開発著しいアフリカにおける環境汚染物質がカバ、リーチェなどの野生動物に及ぼす影響および化学物質感受性の動物種差を明らかにすることを目的とした。[1]ザンビアのサウスルアングア国立公園のカバの肝臓、餌資源である植物、および土壌・河川底質における重金属および有機塩素系物質の蓄積濃度を測定した。カバの肝臓におけるカドミウムおよび水銀濃度は環境サンプルや植物よりも有意に高く、これら毒性金属がカバにおいても生物濃縮している可能性を示した。[2]さらに環境汚染の歩哨動物として野生ラットに注目した。ザンビアのカブウェ鉱床付近の野生ラットでは臓器中に高濃度の鉛やカドミウムの蓄積が見られた。さらに、腎臓におけるMTのmRNA発現量が対照地域の個体と比べて有意に上昇していた。フィールド調査で得られた結果が、土壌汚染が原因であることを明らかにするために、カブエ鉱床地域から土壌を採材し、Wistar rat(オス、30匹)に対して1年間の土壌の暴露試験を行った。土壌非暴露群、低濃度金属含有土壌(鉛:75mg/kg、カドミウム:0.4mg/kg)、および高濃度金属含有土壌(鉛:3757mg/kg、カドミウム:6mg/kg)の3群において金属蓄積濃度、血液生化学検査、および金属暴露のマーカー遺伝子であるMTのmRNA発現量を測定した。高濃度土壌暴露群では、肝臓・腎臓・肺・脳・骨における鉛・カドミウム蓄積濃度が他群と比較して有意に高く、腎臓におけるMTのmRNA発現量も有意に高かった。以上の結果より、鉱床活動由来の土壌汚染がラットにおける金属蓄積および生体反応を引き起こすことが明らかになった。 フィールド調査および室内実験の結果から、カブエ地域では、野生ラットに加えて家畜などのほかの動物やヒトに対する金属汚染の影響が懸念された。以上の研究結果を国際誌2報で報告した。
• Metal concentration and stable isotope ratio analysis (d13C and d15N) in water, sediment and fish from Lake Itezhi-tezhi, Zambia

  財団法人 内藤記念科学振興財団：第10回（2010年度）内藤記念若手研究者海外派遣助成金（春季）

  研究期間 : 2010年04月 -2011年03月 

  代表者 : 中山翔太
• アフリカの野生動物における環境汚染物質の毒性影響評価

  日本学術振興会：科学研究費助成事業 特別研究員奨励費

  研究期間 : 2010年 -2011年 

  代表者 : 中山 翔太

   

  近年の開発著しいアフリカにおける環境汚染物質がカバ、リーチェなどの野生動物に及ぼす影響を明らかにすることを目的とした。[1]ザンビアのサウスルアングア国立公園のカバの肝臓、餌資源である植物、および土壌・河川底質における重金属および有機塩素系物質の蓄積濃度を測定した。カバの肝臓におけるカドミウムおよび水銀濃度は環境サンプルや植物よりも有意に高く、これら毒性金属がカバにおいても生物濃縮している可能性を示した。(Ecotoxicology and Environmental Safety誌、印刷中)[2]さらに環境汚染の歩哨動物として野生ラットに注目した。ザンビアのカブウェ鉱床付近の野生ラットでは臓器中に高濃度の鉛やカドミウムの蓄積が見られた。さらに、腎臓におけるMTのmRNA発現量が対照地域の個体と比べて有意に上昇していた。フィールド調査で得られた結果が、土壌汚染が原因であることを明らかにするために、カブエ鉱床地域から土壌を採材し、Wistar rat(オス、30匹)に対して1年間の土壌の暴露試験を行った。土壌非暴露群、低濃度金属含有土壌(鉛:75mg/kg、カドミウム:0.4mg/kg)、および高濃度金属含有土壌(鉛:3757mg/kg、カドミウム:6mg/kg)の3群において金属蓄積濃度、血液生化学検査、および金属暴露のマーカー遺伝子であるMTのmRNA発現量を測定した。高濃度土壌暴露群では、肝臓・腎臓・肺・脳・骨における鉛・カドミウム蓄積濃度が他群と比較して有意に高く、腎臓におけるMTのmRNA発現量も有意に高かった。以上の結果より、鉱床活動由来の土壌汚染がラットにおける金属蓄積および生体反応を引き起こすことが明らかになった。フィールド調査および室内実験の結果から、カブエ地域では、野生ラットに加えて家畜などのほかの動物やヒトに対する金属汚染の影響が懸念された。
• ザンビア共和国の重金属汚染における毒性学的特徴

  財団法人 国際開発高等教育機構：平成21年度外務省委託研究フェロープログラム（研究発表助成）

  研究期間 : 2009年04月 -2010年03月 

  代表者 : 中山翔太
• 野生鳥類における鉛など毒性金属による汚染実態の解明―安定同位体比による汚染源の解明および分子レベルでの生体影響評価―

  ニッセイ財団：H25年度若手研究・奨励研究

  代表者 : 中山翔太

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