池中 良徳 (イケナカ ヨシノリ)
| Ｏｎｅ Ｈｅａｌｔｈリサーチセンター 高度診断検査部門 | 教授 |
Last Updated :2025/11/06
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経歴
- 2023年10月 - 現在
北海道大学, One Healthリサーチセンター, 教授, 日本国 - 2015年01月 - 現在
ノースウェスト大学 (南アフリカ共和国), 教授, 南アフリカ共和国 - 2021年04月 - 2023年09月
北海道大学大学院獣医学研究院附属動物病院トランスレーショナルリサーチ推進室, 教授, 日本国 - 2015年12月 - 2021年03月
北海道大学, (連合)獣医学研究科, 准教授 - 2011年01月 - 2015年11月
北海道大学（連合）獣医学研究科, 講師 - 2009年04月 - 2009年07月
北海道大学（連合）獣医学研究科, 博士研究員 - 2008年04月 - 2009年03月
北海道大学, 日本学術振興会 特別研究員(PD) - 2007年04月 - 2008年03月
信州大学, 日本学術振興会 特別研究員（DC2）
学歴
委員歴
■研究活動情報
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論文
- Evaluation of ascorbic acid as an intervention of metal toxicity in dogs in Kabwe district.
Nelly Banda, Mahongo Selwa, Rio Doya, Nyein Chan Soe, Andrew Kataba, John Yabe, Golden Zyambo, Kaampwe Muzandu, Yared Beyene Yohannes, Yoshinori Ikenaka, Mayumi Ishizuka, Shouta Mm Nakayama
Veterinary and animal science, 30, 100519, 100519, 2025年12月, ［国際誌］
英語, 研究論文（学術雑誌）, Non-essential metals and metalloids are known to induce oxidative stress in exposed organisms, often leading to cellular damage and systemic toxicity. While chelation therapy remains the primary treatment for metal toxicity, its application is limited by side effects. L-ascorbic acid (L-AA), a widely available antioxidant, has emerged as a promising nutritional intervention for mitigating metal-induced oxidative stress. Dogs, whose blood lead levels (BLLs) closely mirror those of humans, have been utilized as sentinel species in environmental toxicology studies. This study aimed to evaluate the therapeutic potential of L-AA in dogs residing in Kabwe, Zambia, a former mining town where remediation of heavy metal contamination is ongoing. The reported BLLs in Kabwe dogs ranged from 0.43 µg/dL to 123.5 µg/dL. A total of 22 dogs (10 females and 12 males) received oral L-AA supplementation daily for 14 days. Blood samples were collected on Day 1 of L-AA administration and Day 14 to assess biochemical and toxicological changes. Post-treatment analysis revealed statistically significant reductions in plasma malondialdehyde, cortisol, blood urea nitrogen, and creatinine levels, as determined by Student's t-test and Wilcoxon signed-rank test. Additionally, δ-aminolaevulinic acid dehydratase activity was significantly elevated, indicating improved oxidative status. These findings support the efficacy of L-AA in attenuating oxidative stress associated with metal and metalloid exposure, even in the absence of exposure cessation. Interestingly, Pb levels declined predominantly in dogs younger than 24 months. Furthermore, reductions in Zn and Cu commonly linked to L-AA administration were observed exclusively in male dogs, suggesting a sex-specific response. - Forensic detection and quantification of methomyl in animal stomach contents using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS) in Japan.
Yared Beyene Yohannes, Aki Tanaka, Yuko Kihara, Tsuyoshi Tajima, Shouta Nakayama, Collins Nimako, Yoshinori Ikenaka, Mayumi Ishizuka
The Journal of veterinary medical science, 2025年10月29日, ［国内誌］
英語, 研究論文（学術雑誌）, Pesticide poisoning in animals is a rising forensic issue due to widespread chemical use. This study analyzed stomach contents from 44 deceased animals (domestic and wild) in Japan using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS) for non-targeted screening and liquid Chromatography tandem mass spectrometry (LC-MS/MS) for quantification after Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) extraction. Non-target screening detected multiple pesticide classes, with carbamates and herbicides being the most prevalent. Methomyl was identified in 29 cases (65.9%), with concentrations up to 157 mg/kg in cats, 75 mg/kg in a civet, and 30 mg/kg in a dog, exceeding the oral LD₅₀ of methomyl in dogs (10 mg/kg) and cats (estimated to be similar). These findings suggest acute poisoning and possible intentional misuse. The toxicological significance of methomyl highlights the need for stricter regulations, better monitoring, and increased public awareness to prevent further animal poisonings. - Effects of Imidacloprid on Afrotropical Aquatic Ecosystems: A South African Microcosm Study.
Marelize Marsay, Paul J van den Brink, Collins Nimako, Yoshinori Ikenaka, Mayumi Ishizuka, Victor Wepener
Integrated environmental assessment and management, 2025年09月08日, ［国際誌］
英語, 研究論文（学術雑誌）, Pesticides are widely used to meet the food demands of a growing population, with various types used to control pests depending on the crops grown. Rainfall, overspray, and runoff from agricultural fields can wash these insecticides into water bodies, posing documented environmental risks. Imidacloprid is commonly used in Afrotropical regions such as South Africa, yet limited information is available on its toxicity to aquatic ecosystems within this climate region. To address this, a 16-week outdoor microcosm study was conducted, exposing aquatic communities to 0.1, 10 and 250 µg/L imidacloprid under natural conditions. Physicochemical parameters, such as pH, dissolved oxygen, temperature, and various others, were monitored regularly. The microbial community, organic decomposition and zooplankton were largely unaffected by the exposure to imidacloprid. In contrast, 10 and 250 µg/L of imidacloprid led to long-term effects on the macroinvertebrate community, while short-term effects were found in the 0.1 µg/L treatment. Families such as Coenagrionidae were affected across all treatments, while Caenidae and Notonectidae were only affected in the highest treatment. Changes in the community structure resulted in reduced predator abundance (such as Coenagrionidae, Libellulidae and Notonectidae) and increased filter feeders (Culicidae). High temperatures likely increase the toxicity to arthropods when compared to similar studies with lower light intensities and temperatures. Recovery was limited during the post-exposure period, with some families (Baetidae) rebounding quickly, while others, Caenidae and Coenagrionidae, showed delayed recovery. Full recovery of the macroinvertebrate community systems did not occur during the 8-week recovery period, highlighting the importance of unexposed refuges for recolonization. This study provides important field-realistic evidence of the ecological risks associated with imidacloprid use in Southern African freshwater systems. - Evaluation of Neurotoxicity of Neonicotinoid Insecticides Using Lipidomics.
Tomoya Koike, Anri Hirai, Kei Nomiyama, Akihumi Eguchi, Nobuhiko Hoshi, Tetsushi Hirano, Collins Nimako, Yared Beyene Yohannes, Mai Tamba, Shouta M M Nakayama, Mayumi Ishizuka, Yoshinori Ikenaka
Environmental toxicology and chemistry, 44, 11, 3212, 3224, 2025年08月09日, ［国際誌］
英語, 研究論文（学術雑誌）, Neonicotinoid (NN) pesticides are widely used globally, but recent studies suggest that even non-toxic doses can induce anxiety-like behaviors and alter brain monoamine neurotransmitter levels in mice. Current neurotoxicity assays may fail to detect subtle toxic effects, such as higher brain function abnormalities caused by small molecule disruptions. These findings highlight the need for highly sensitive and reproducible neurotoxicity testing methods. The brain, a lipid-rich organ, relies on lipids for various functions, and disturbances in lipid homeostasis are linked to numerous diseases. This study uses lipidomics to analyze the cerebral cortex of mice exposed to the NN acetamiprid (ACE), aiming to identify lipid biomarkers of neurotoxicity. Thirty 12-week-old male C57BL/6J mice were randomly divided into control (0 mg/kg), low dose (65 mg/kg), and high dose (130 mg/kg) groups, with 10 mice in each group. Mice were euthanized, and cerebral cortex samples were collected 30 minutes after oral ACE administration. Lipids were extracted and analyzed using Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (LC/Q-TOF/MS). A total of 358 lipids were annotated. Fifteen lipids exhibited a fold change > 2.0 and significant differences between control and high-dose groups, with an AUC ≥ 0.900 in ROC analysis. Increased levels of seven fatty acids (e.g., palmitic acid) and five Fatty Acyl Esters of Hydroxy Fatty Acids (e.g., FAHFA 22:6_22:5) were observed, suggesting roles in neurodegenerative diseases and inflammation. These findings identify a promising lipid biomarker linked to NN-induced neurotoxicity and contribute to detecting neurotoxic effects from acute exposure to such substances. - Anthropogenic Activities Elevate Heavy Metals Levels in Soil and Tree Bark; A Case Study of Lower Zambezi and Mosi-Oa-Tunya National Parks.
Nelly Banda, Kanami Watanabe, Rio Doya, Nyein Chan Soe, Andrew Kataba, John Yabe, Golden Zyambo, Kaampwe Muzandu, Yared Beyene Yohannes, Yoshinori Ikenaka, Mayumi Ishizuka, Shouta M M Nakayama
Archives of environmental contamination and toxicology, 89, 2, 180, 194, 2025年08月, ［国際誌］
英語, 研究論文（学術雑誌）, The impact of various human activities on protected environments remains a significant concern. Mining for ores is crucial in many aspects of society. To achieve global decarbonisation, more metals are required, which will lead to increased worldwide metal exploration and mining. Zambia is primarily a mining country and has expanded exploration into protected lands (national parks). The effects of this exploration on these protected areas is ongoing. This study aimed to establish baseline data for monitoring metal pollution in the Lower Zambezi National Park before mining commenced. It also evaluated whether tourism influenced metal pollution in national parks and how these metals and metalloids correlate within tree bark and soils. To accomplish this, soil and Acacia tree bark samples were collected from Lower Zambezi National Park and Mosi-Oa-Tunya National Park. Arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn) were analysed in this study. The concentrations of metals and metalloids were higher in areas with vehicular traffic and mining activity in the national parks, which may directly impact the biosystems in those areas. Maximum levels of metals in soil in these areas were as follows: As 40.8 mg/kg, Cd 0.879 mg/kg, Cr 241 mg/kg, Hg 1.1 mg/kg, Pb 211 mg/kg, and Zn 1285 mg/kg. When compared to areas of lower anthropogenic activities, differences in metal concentrations were up to 1000-fold. These changes can potentially affect the adaptation of wildlife to various stressors, especially as we are facing global climate change. - Human plasma protein bindings of neonicotinoid insecticides and metabolites.
Kumiko Taira, Yoshinori Ikenaka, Jean-Marc Bonmatin, Anton Safer
Scientific reports, 15, 1, 13155, 13155, 2025年04月16日, ［国際誌］
英語, 研究論文（学術雑誌）, Neonicotinoid insecticides (neonicotinoids) are widely used in agriculture, forestry and public health in the world. Environmental exposure to neonicotinoids has been increasing due to their continuous uses. Neonicotinoids act as agonists, antagonists, or modulators of acetylcholine receptors and have adverse effects on non-target species, such as invertebrates, amphibians, reptiles, birds, microbes and mammals. Although there is concern about their adverse effects on ecosystem services and their potential effects on human health, their xenobiotic kinetics and dynamics in humans are not understood well. In this study, we determined a xenobiotic kinetic parameter, plasma protein bindings (PPBs) of 7 neonicotinoids and 18 metabolites with human plasma using a Rapid Equilibrium Dialysis (RED) device and liquid chromatography-tandem mass spectrometry (LC-MS/MS), and compared their PPBs with their physicochemical properties. 6-chloronicotinic acid (6-CNA) exhibited the highest PPB (86.4%), followed by imidacloprid-olefin (86.3%) in human plasma. Their PPBs are much higher than that of the parent compound, imidacloprid (27.5%). The PPBs of neonicotinoids and metabolites are not related to their lipophilicity determined by reversed-phase LC. The results shed light on the behavior of environmentally exposed neonicotinoids and metabolites and warrant further research on their xenobiotic kinetics and dynamics in humans. - Associations between urinary phthalate metabolites and reproductive, adrenal, and gonadotropic hormones in peripubertal children: the Hokkaido study.
Ayaka Yasuda, Yu Ait Bamai, Takeshi Yamaguchi, Rahel Mesfin Ketema, Yi Zeng, Megasari Marsela, Yoshinori Ikenaka, Akie Nakamura, Takeya Kitta, Masafumi Kon, Atsushi Manabe, Reiko Kishi, Hiroyuki Kojima, Atsuko Ikeda
Environmental research, 276, 121535, 121535, 2025年04月03日, ［国際誌］
英語, 研究論文（学術雑誌）, Phthalates have raised concerns regarding the disruption of hormone synthesis and signaling. The purpose of this study was to investigate the associations between urinary phthalate metabolites and 18 hormones, including reproductive, adrenal, and gonadotropic hormones, in peripubertal children. The study comprised a cross-sectional analysis of participants in the Hokkaido Birth Cohort Study. We collected data from 429 school children aged 9-12 living in Sapporo, Japan. Ten phthalate metabolites and 14 steroid hormones were analyzed using LC-MS/MS, whereas four peptide hormones were detected using immunoassays. Multivariable linear regression, quantile-based g-computation (qg-computation), and Bayesian kernel machine regression (BKMR) were used to investigate the associations between the individual phthalate metabolites and the phthalate mixtures with hormone levels, as well as with puberty based on hormone levels. In girls, we found that higher phthalate metabolite levels, as well as phthalate mixtures, were significantly associated with lower dehydroepiandrostenedione-sulfate (DHEA-S) and higher (androstenedione + testosterone) / DHEA-S. The higher phthalate mixture showed lower levels of LH, FSH, and cortisol levels among girls, whereas higher 11-deoxycortisol levels. In boys, a higher phthalates mixture was significantly associated with a higher estradiol/testosterone ratio, whereas lower levels of insulin-like factor-3 (INSL3), testosterone, (androstenedione + testosterone)/DHEA-S, testosterone/androstenedione, and cortisol/cortisone. Higher phthalate mixtures were associated with lower prevalence of puberty in girls. These findings indicate that phthalate exposure may disrupt the hormones in children during puberty. - Assessing the efficacy of phosphate and lime amendments in immobilizing three forms of lead in contaminated soil: An in vivo study on C57/BL6 mice simulating environmentally realistic exposure pathways.
Nyein Chan Soe, Takashi Fujimori, Kenji Shiota, Rio Doya, Walubita Mufalo, Mayumi Ito, Tsutomu Sato, Toshifumi Igarashi, Yoshinori Ikenaka, Mayumi Ishizuka, Shouta M M Nakayama
Chemosphere, 374, 144201, 144201, 2025年04月, ［国際誌］
英語, 研究論文（学術雑誌）, Lead (Pb) bioavailability differs depending on the specific Pb species present in the area. Adding organic and inorganic soil amendments can ameliorate the mobility of Pb in the soil. However, there is a scarcity of in vivo studies investigating the impact of these amendments on mammals via environmentally realistic exposure pathways. We evaluated the accumulation of Pb in blood and tissues of mice living on soils spiked with one of three Pb species (hydrocerussite [2PbCO3·Pb(OH)2], lead sulfate [PbSO4], and lead sulfide [PbS]) and compared the efficacy of phosphate (triple super phosphate [TSP] or phosphoric acid) or liming (calcined dolomite) amendments in reducing Pb accumulation from these soils via realistic exposure pathways. The Pb species in the spiked soil were investigated via X-ray absorption near edge structures (XANES) spectroscopy. C57/BL6 mice (six per group) were exposed to both Pb-spiked and amended soils by housing them on the soil for three months and thus simulating realistic exposure pathways. XANES analysis revealed that Pb carbonates were the dominant phase in all Pb-spiked soils. The group exposed to 2PbCO3·Pb(OH)2 had the greatest Pb accumulation in brain, trachea, kidneys, liver, bone, and blood, but not lungs, whereas the PbS-exposed group accumulated more Pb in the lungs. TSP was the most effective chemical stabilizer of the three amendments, facilitating reductions in the 2PbCO3·Pb(OH)2, PbSO4, and PbS exposure groups of 68-88%, 44-62%, and 6-49%, respectively. This suggests that chemical remediation using phosphate sources may be effective for immobilizing various Pb species in soils. - Pollution and partitioning of neonicotinoid insecticides in free-grazing ducks and their eggs: Implications for human health.
Collins Nimako, Kraisiri Khidkhan, Sittinee Kulprasertsri, Saranya Poapolathep, Paphatsara Khunlert, Yared B Yohannes, Yoshinori Ikenaka, Shouta M M Nakayama, Mayumi Ishizuka, Amnart Poapolathep
Environmental pollution (Barking, Essex : 1987), 373, 126099, 126099, 2025年03月20日, ［国際誌］
英語, 研究論文（学術雑誌）, Neonicotinoid insecticides are used extensively in many pest control schemes across the globe; but little is known about their impacts on free-grazing domestic birds and the quality of meat or eggs produced from such birds. This study assessed the pollution and partitioning of neonicotinoids in serum and eggs of free-grazing ducks from 5 provinces of Thailand and elucidated the associated human health implications. Biological samples (duck serum, egg albumins, and egg yolks) and environmental samples (soil, water, feed) were collected from 9 duck farms in Thailand and subjected to LC/MS/MS analysis. Out of 6 neonicotinoid compounds targeted, five were detected in duck serum. Imidacloprid had the greatest median concentration of 1.4 ng/mL and the highest detection frequency (df) of 85.8 % in the ducks' serum, followed by acetamiprid (median concentration = 0.4 ng/mL; df = 2.8 %), clothianidin (median concentration = 0.2 ng/mL; df = 9.4 %) or thiamethoxam (median concentration = 0.2 ng/mL; df = 7.5 %) and dinotefuran (only one sample was contaminated with 6.3 ng/mL of dinotefuran). The neonicotinoids were similarly detected in soil, water, and feed samples obtained from the duck farms, suggesting that the ducks were exposed to the insecticides from the nearby agricultural fields. The neonicotinoid compounds selectively accumulated in the albumin of duck eggs compared to yolk. The median concentration ratios of albumin to yolk obtained for imidacloprid, dinotefuran, thiamethoxam, clothianidin, and acetamiprid were 694, 463, 458, 382, and 263, respectively. However, upon human health risk analysis, levels of neonicotinoids detected in duck eggs were not found to present any appreciable risks to duck egg consumers. - Phosphate Flame Retardants and Plasticizers and Their Association with Reproductive and Steroid Hormone Levels among Peripubertal-Aged Children: The Hokkaido Birth Cohort Study.
Atsuko Ikeda, Takeshi Yamaguchi, Yu Ait Bamai, Maarten Roggeman, Yoshinori Ikenaka, Yi Zeng, Ayaka Yasuda, Rahel Mesfin Ketema, Megasari Marsela, Celine Gys, Fatima den Ouden, Sachiko Itoh, Akie Nakamura, Takeya Kitta, Masafumi Kon, Atsushi Manabe, Adrian Covaci, Reiko Kishi
Environmental science & technology, 59, 10, 4820, 4831, 2025年03月18日, ［国際誌］
英語, 研究論文（学術雑誌）, This cross-sectional study investigated associations between exposure to organophosphate flame retardants and plasticizers (PFRs) and reproductive and steroid hormones in peripubertal children from the Hokkaido Birth Cohort (429 children aged 9-12 years; between September 2017 and March 2020). Thirteen urinary PFR metabolites and 14 plasma steroid hormones were investigated using LC-MS/MS and four reproductive hormones were investigated using immunoassays. Linear regression for single PFR, quantile g-computation, and Bayesian machine kernel regression (BKMR) models for the PFR mixtures were used to examine the association between hormones and PFRs. Among boys, significant positive associations were observed between estradiol and ΣTCIPP and ΣTBOEP, and inverse associations were identified between insulin-like factor-3 (INSL3) and ΣTCIPP, and between luteinizing hormone (LH) and ΣEHDPHP. The PFR mixture was associated with the trends of increasing estradiol and androstenedione, and decreasing cortisol, cortisone, LH, inhibin B, and INSL3. Among girls, androstenedione and ΣTCIPP, testosterone and ΣEHDPHP, (androstenedione + testosterone)/DHEA-S and ΣTCIPP, and ΣEHDPHP and ΣTPHP were significantly correlated. The PFR mixture showed trends of increasing testosterone, androstenedione, and inhibin B, and decreasing cortisol, cortisone, and INSL3. Individual PFRs and PFR mixtures altered steroids and reproductive hormones in peripubertal children. - Anticoagulant rodenticide accumulation in the liver and plasma of pigeons (Columba livia) in Thailand.
Kosal Phourng, Ratiwan Sitdhibutr, Yared Beyene Yohannes, Yoshinori Ikenaka, Aksorn Saengtienchai
Open veterinary journal, 15, 8, 3608, 3617, 2025年, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Anticoagulant rodenticides (ARs) are widely used worldwide to control rodents. Currently, many countries are considering the use of ARs, which results in widespread accumulation and poisoning of nontarget animals. Nontarget pigeons (Columba livia) typically live near human communities and agricultural areas. These birds are at high risk of accidental daily exposure to ARs. AIM: This study aimed to evaluate ARs in the liver and plasma of pigeons living in rural and urban areas of Thailand. METHODS: Bird samples were characterized by sampling location, age, body weight (BW), and body condition score. Liver and plasma samples were extracted using liquid-liquid extraction with diethyl ether and analyzed for coumatetralyl and warfarin by liquid chromatography-mass spectrometry. RESULTS: Coumatetralyl and warfarin were detected in pigeons from both rural and urban areas. Both subadult and adult birds showed the presence of these two compounds, which were mainly detected in rural areas. The increase in BW was compared with the accumulation of coumatetralyl and warfarin, and a significant difference was observed. In addition, the concentration of coumatetralyl was significantly higher in the liver than in the plasma. The plasma concentrations of coumatetralyl and warfarin were 0.19-0.50 and 0.12-2.41 ng/ml, respectively. In the liver, coumatetralyl levels were higher than those of warfarin, with concentrations ranging from 0.07- to 3.33-ng/g wet weight and from 0.12- to 0.50-ng/g wet weight. CONCLUSION: AR use in human settlements and agricultural areas poses a high risk of accumulation in nontarget animals, such as pigeons. The findings of this study indicate coumatetralyl and warfarin in various concentrations in pigeon hepatic and plasma samples. - Effect of the neonicotinoid pesticide clothianidin at a no-observed-adverse-effect-level (NOAEL) dose on maternal behavior in pregnant mice and their female offspring
Sarika NUNOBIKI, Ayano YOSHIMOTO, Makiko ITO, Sakura YONOICHI, Yukako HARA, Yuya ISHIDA, Rinako MORISHITA, Youhei MANTANI, Toshifumi YOKOYAMA, Tetsushi HIRANO, Yoshinori IKENAKA, Nobuhiko HOSHI
Journal of Veterinary Medical Science, 87, 4, 411, 418, Japanese Society of Veterinary Science, 2025年, ［国内誌］
英語, 研究論文（学術雑誌）, Our previous reports showed that exposure to the neonicotinoid pesticide clothianidin (CLO) at a no-observed-adverse-effect-level (NOAEL) dose during fetal development and lactation in mice led to higher rates of maternal neglect and infanticide. Although the demonstrated association between decreased oxytocin secretion and decreased maternal parenting behavior implies a link to declining oxytocin levels, no evidence has yet emerged in CLO to clearly establish such an association. This study investigated the effects of CLO on maternal behavior and oxytocin in C57BL/6N mice exposed during pregnancy and lactation (F0 mothers) as well as in their adult female offspring (F1 mothers). The effects were assessed using nest building assays during pregnancy and pup retrieval assessment after delivery. The results showed a decrease in oxytocin secretion and a marked decrease in pup retrieval behavior among the F0 mothers in the CLO exposure group compared to those in the control group. Their offspring, the F1 mothers, showed significantly lower nest-building scores during pregnancy. In conclusion, this study is the first to examine the potential mechanisms by which CLO exposure in mothers at the NOAEL dose during pregnancy and lactation results in reduced plasma oxytocin levels, subsequently leading to a decline in maternal behaviors such as pup retrieval. Furthermore, these effects may impair maternal behaviors in the next generation, when the offspring mice become mothers. - Effects of low-dose subchronic exposure to the phenylpyrazole insecticide fipronil in juvenile mice
Ayano YOSHIMOTO, Sarika NUNOBIKI, Makiko ITO, Sakura YONOICHI, Yukako HARA, Yuya ISHIDA, Youhei MANTANI, Toshifumi YOKOYAMA, Tetsushi HIRANO, Yoshinori IKENAKA, Nobuhiko HOSHI
Journal of Veterinary Medical Science, 87, 4, 419, 425, Japanese Society of Veterinary Science, 2025年, ［国内誌］
英語, 研究論文（学術雑誌）, Fipronil (FPN) inhibits gamma-aminobutyric acid type A receptors and exhibits strong insecticidal effects. Although FPN's adverse effects on mammals have been reported recently, few studies have examined subchronic exposure to low doses. We orally administered FPN (0.43 mg/kg) to 4-week-old male mice for 6 wk and assessed their behavior and blood characteristics. Compared with the control group, the FPN-treated group presented reduced weight gain but upward trends in locomotor activity and blood histamine levels. Fipronil sulfone (FPNS) was detected in all individuals, whereas FPN was not detected in any individual. The present study shows for the first time that subchronic exposure to low-dose FPN in mice led to FPNS conversion in the body, affecting weight gain and behavior. - Sex dependent intergenerational effects of lead in mouse model.
Nelly Banda, Nyein Chan Soe, John Yabe, Rio Doya, Yared Beyene Yohannes, Yoshinori Ikenaka, Mayumi Ishizuka, Shouta M M Nakayama
Scientific reports, 14, 1, 30233, 30233, 2024年12月04日, ［国際誌］
英語, 研究論文（学術雑誌）, Lead (Pb) exposure negatively impacts fertility in both males and females, pregnancy outcomes, and child brain development. We investigated the reproductive and neurological effects of Pb exposure on male and female mice via Pb-contaminated soil for 4 weeks. Breeding was conducted after completion of exposure, in four groups; group 1 consisted of exposed dams and unexposed sires, group 2 consisted of exposed sires and unexposed dams, group 3 consisted of exposed sires and exposed dams and group 4 was the control. Generally, Pb exposure reduced observed conception rates, with a cumulative decrement observed when both males and females are exposed. Gene expression of the testes revealed oxidative stress as the cause of reduced conception rates. Neurological tests: Morris water maze and rotarod were conducted on F1 generation offspring. Maternally and paternally exposed F1 mice performed poorly in the Morris water maze when compared to the control. The severity of the neurological effects was also parent-dependent and sex-dependent. Paternal Pb exposure effects were more pronounced in female offspring. A comparison of gene expression changes of the hippocampus and prefrontal cortex showed paternal Pb-exposure resulted in more prefrontal cortex changes than in the hippocampus, a trend also recorded in the exposed sires. The pronounced effects in female offspring of paternal Pb exposure may suggest that Pb neurological effects may be X-chromosome-linked. - Investigating drug residues in Mongolian milk using a newly developed method with high performance liquid chromatography and a photo diode array.
Delgermurun Dugar, Kodai Motohira, Nyamsuren Purevdorj, Bolormaa Pelden, Shouta Mm Nakayama, Mayumi Ishizuka, Yoshinori Ikenaka
The Journal of veterinary medical science, 87, 1, 103, 109, 2024年10月14日, ［国内誌］
英語, 研究論文（学術雑誌）, Despite the beneficial impacts of using drugs in animal husbandry, the risks of drug residues in animal products are a concern worldwide. Therefore, most countries have developed systems and methods to detect and monitor drug residues in animal products using high performance liquid chromatography (HPLC) with mass spectrometry (MS). However, MS detectors are not available in all universities; thus, we developed a new method suitable for ultraviolet detection. We first validated a new method targeting tetracycline and albendazole in milk and evaluated these drug residues in 50 samples collected from farms and supermarkets in Mongolia. The practical limit of quantification (PQL) calculated in our newly developed method was suitable to detect the maximum residual limits defined in Codex Alimentarius, and the accuracy and precision of a new method were comparable to previous studies. In particular, inter-day analysis showed great precision, with albendazole showing a 99% recovery rate with ± 3.3 of relative standard deviation (RSD). In addition, we evaluated our drugs contamination, but targeted drugs residues were not detected in the current sample set. However, this may reflect the decreased use of tetracycline in the veterinary field and seasonal use of albendazole in Mongolia. Therefore, these drugs must be continuously monitored. To the best of our knowledge, this is the first report about drug residues in milk published in an international journal by a Mongolian domestic institution. Further investigations of drug residue in Mongolia are urgently needed. - Effect of Java plum (Syzygium cumini) leave extract and a silver nanoparticles synthesis on pathogens in skin diseases of dogs.
Namthip Wongstitwilairoong, Usuma Jermnark, Napasorn Paochoosak, Orawan Limsivilai, Wissanuwat Chimnoi, Yared Beyene Yohannes, Yoshinori Ikenaka, Aksorn Saengtienchai
Open veterinary journal, 14, 10, 2662, 2677, 2024年10月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Antibiotic use has been rising in both humans and animals. The growing concern over antimicrobial drug resistance and the promotion of regional drug use have led to a rise in the interest in medicinal applications of herbs combined with biosynthesized nanoparticles. AIM: To evaluate the antimicrobial and acaricidal effects of Syzygium cumini leaves crude extract (Sc-CE) and biosynthesized S. cumini silver nanoparticles (Sc-AgNPs) on dog skin pathogens and determined the optimal concentration and time for in vitro application. METHODS: Syzygium cumini leaves (Sc) were prepared as Sc-CE and Sc-AgNPs. The biosynthesized silver nanoparticles were characterized employing various techniques, including dynamic light scattering, scanning electron microscopy, and energy-dispersive X-ray analysis. Phytochemical analyses were conducted using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry screening. Antimicrobial activity was examined against gram-positive bacteria, including Staphylococcus aureus and Staphylococcus pseudintermedius, gram-negative bacteria such as Pseudomonas aeruginosa, yeast strains including Malassezia pachydermatis and Candida albicans, and ectoparasite. Cytotoxicity was evaluated on canine primary dermal fibroblast (CPDF) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS: The Sc-AgNPs exhibited nanoparticle sizes ranging from 100 to 350 nm with aggregated spherical shape and contained Ag element in this nanoparticle. Myricetin and Phloretin were among the extracted compounds, contributing to the reduction of pathogenic organisms. Sc-AgNPs showed high efficacy against skin pathogens compared to Sc-CE, with a lower cytotoxicity effect on CPDF. CONCLUSION: The Sc-AgNPs demonstrated superior efficiency against pathogens in dog skin diseases as both concentration- and time-dependent and were deemed safe to CPDF within 24 hours. - Reference intervals for urinary metanephrines to creatinine ratios in dogs in Japan.
Noriyuki Nagata, Yoshinori Ikenaka, Hiryu Sawamura, Noboru Sasaki, Mitsuyoshi Takiguchi
The Journal of veterinary medical science, 86, 10, 1096, 1099, 2024年09月03日, ［国内誌］
英語, 研究論文（学術雑誌）, The urinary normetanephrine to creatinine ratio (uNMN/Cr) and urinary metanephrine to creatinine ratio (uMN/Cr) are commonly evaluated for the diagnosis of pheochromocytomas (PCC) in dogs. This study aimed to establish reference intervals for uNMN/Cr and uMN/Cr in 56 healthy dogs in Japan and to investigate the effect of urine collection methods on these measurements in 15 non-PCC dogs. The upper limits of reference intervals for uNMN/Cr and uMN/Cr were 124.4 nmol/mmol (90% confidence interval [CI] 107.7-137.0) and 121.1 nmol/mmol (90% CI 102.8-145.1), respectively. Both uNMN/Cr and uMN/Cr were significantly higher when urine was collected in the hospital compared to at home. Several factors, including the method of urine collection, should be considered when utilizing these reference intervals. - Characterization of Neonicotinoid Metabolites by Cytochrome P450-Mediated Metabolism in Poultry.
Adisorn Dam-On, Collins Nimako, Sittinee Kulprasertsri, Yoshinori Ikenaka, Yared B Yohannes, Shouta M M Nakayama, Mayumi Ishizuka, Saranya Poapolathep, Amnart Poapolathep, Kraisiri Khidkhan
Toxics, 12, 8, 2024年08月21日, ［国際誌］
英語, 研究論文（学術雑誌）, Neonicotinoids, a neuro-effective class of insecticides, are heavily applied in agricultural activities worldwide. Poultry can be exposed to neonicotinoids by several routes, but the knowledge of neonicotinoid's metabolism in poultry and its associated interspecies differences is highly limited. Hence, this study aims to investigate the species differences in metabolite formations, as well as cytochrome P450 (CYP)-dependent metabolism of four major neonicotinoid compounds, acetamiprid, imidacloprid, clothianidin, and thiamethoxam, in poultry. In vitro biotransformation assays using hepatic microsomes of chicken, ducks, geese, quails, and rats were conducted. Metabolites of neonicotinoids were then screened by LC/Q-TOF and quantified by LC/MS/MS. The results revealed an existence of interspecies differences in the formations of N-[ (6-chloro-3-pyridyl) methyl] -N-methyl acetamidine (IM-1-5) of acetamiprid and dm-clothianidin of clothianidin between chicken and other species. In addition, the greatest CYP activities in the metabolism of most neonicotinoid substrates, such as acetamiprid to dm-acetamiprid, imidacloprid to hydroxylated-imidacloprid and imidacloprid-olefin, clothianidin to dm-clothianidin, and thiamethoxam to clothianidin, were found in chicken. These results suggested that the CYPs in chicken may have a greater capacity for metabolism of neonicotinoids compared to other poultry. This study further revealed that the maximum intrinsic clearance of dn-imidacloprid and dn-clothianidin in ducks may be superintended by CYP-mediated nitro-reductions of imidacloprid and clothianidin. Further studies employing CYP recombinant enzymes may be required to elucidate the specific CYP isoforms that may be involved in neonicotinoid metabolism in avian species. - FOUR-WEEK ORAL ADMINISTRATION OF BALOXAVIR MARBOXIL AS AN ANTI-INFLUENZA VIRUS DRUG SHOWS NO TOXICITY IN CHICKENS
Miki M, Obara RD, Nishimura K, Shishido T, Ikenaka Y, Oka R, Sato K, Nakayama SMM, Kimura T, Kobayashi A, Aoshima K, Saito K, Hiono T, Isoda N, Sakoda Y
J Zoo Wildl Med, 55, 2, 313, 321, 2024年06月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, High pathogenicity avian influenza is an acute zoonotic disease with high mortality in birds caused by a high pathogenicity avian influenza virus (HPAIV). Recently, HPAIV has rapidly spread worldwide and has killed many wild birds, including endangered species. Baloxavir marboxil (BXM), an anti-influenza agent used for humans, was reported to reduce mortality and virus secretion from HPAIV-infected chickens (Gallus domesticus, order Galliformes) at a dosage of ≥2.5 mg/kg when administered simultaneously with viral challenge. Application of this treatment to endangered birds requires further information on potential avian-specific toxicity caused by repeated exposure to BXM over the long term. To obtain information of potential avian-specific toxicity, a 4-wk oral repeated-dose study of BXM was conducted in chickens (n = 6 or 7 per group), which are commonly used as laboratory avian species. The study was conducted in reference to the human pharmaceutical guidelines for nonclinical repeated-dose drug toxicity studies to evaluate systemic toxicity and exposure. No adverse changes were observed in any organs examined, and dose proportional increases in systemic exposure to active pharmaceutical ingredients were noted from 12.5 to 62.5 mg/kg per day. BXM showed no toxicity to chickens at doses of up to 62.5 mg/kg per day, at which systemic exposure was approximately 71 times higher than systemic exposure at 2.5 mg/kg, the reported efficacious dosage amount, in HPAIV-infected chickens. These results also suggest that BXM could be considered safe for treating HPAIV-infected endangered birds due to its high safety margin compared with the efficacy dose. The data in this study could contribute to the preservation of endangered birds by using BXM as a means of protecting biodiversity. - Urinary steroid profiling using liquid chromatography-tandem mass spectrometry for the diagnosis of canine Cushing's syndrome.
N Nagata, H Sawamura, Y Ikenaka, K Morishita, K Hosoya, N Sasaki, K Nakamura, M Takiguchi
Veterinary journal (London, England : 1997), 106151, 106151, 2024年05月29日, ［国際誌］
英語, 研究論文（学術雑誌）, Serum cortisol measurements by chemiluminescence enzyme immunoassay (CLEIA) are widely used to diagnose hypercortisolism (HC) or Cushing's syndrome in dogs. However, they are associated with problems such as the need for multiple blood collections under stressful conditions or cross-reactivity between hormones. Therefore, a less invasive and more accurate diagnostic method is required. This study aimed to develop a urinary steroid profile analysis method using liquid chromatography-tandem mass spectrometry (LC/MS/MS) and to evaluate its clinical usefulness. Sixty-five healthy dogs and 38 dogs with suspected HC were included in the study. Using LC/MS/MS, the levels of 11 steroid hormones in the urine were determined. We established the upper limit of the reference interval for each urinary steroid-to-creatinine ratio and evaluated their diagnostic performances. The levels of the five steroid hormones were significantly higher in the 14 dogs with HC than in the 24 dogs with mimicking HC and 65 healthy dogs. The urinary corticosterone-to-creatinine ratio showed the highest diagnostic accuracy (area under the curve, 0.96). A significant correlation was seen between urinary cortisol concentrations measured by LC/MS/MS and CLEIA (rs = 0.88, P <0.001), although the CLEIA measurements were significantly higher than the LC/MS/MS measurements (P <0.001). LC/MS/MS-based urinary steroid profiles are a promising tool for diagnosing canine HC. - Role of brain monoamines in acetamiprid-induced anxiety-like behavior.
Anri Hirai, Chitoku Toda, Yared Beyene Yohannes, Nimako Collins, Mai Tamba, Kei Nomiyama, Akifumi Eguchi, Nobuhiko Hoshi, Tetsushi Hirano, Shouta M M Nakayama, Mayumi Ishizuka, Yoshinori Ikenaka
Toxicology, 505, 153839, 153839, 2024年05月21日, ［国際誌］
英語, 研究論文（学術雑誌）, Neonicotinoid (NN) pesticides have been linked to increased brain dysfunction in mammals, such as anxiety-like behavior; this is thought to involve monoamines (MA), neurotransmitters that control behavior, memory, and learning. However, the mechanism by which NNs affect the central nervous system is not fully understood. In this study, we aimed to investigate whether MAs affect NNs-induced anxiety-like behavior. Mice were orally administered acetamiprid (ACE), an NN, at the no observed adverse effect level (NOAEL) of mouse (20mg/kg body mass) set by the Food Safety Commission of Japan, and the elevated zero-maze (EZM) test was performed 30min after administration. After behavioral analysis, levels of four MA (dopamine, 3-MT, serotonin, and histamine) in selected brain regions were determined by liquid chromatography mass spectrometry (LC/MS/MS). In the exposed group, a trend toward increased anxiety-like behavior was observed, and at least one MA concentration was significantly increased in each region. Further, significant correlations were found between behavioral test results and hippocampal serotonin and striatal dopamine concentrations, as well as between dopamine and serotonin concentrations, in the exposed group. As anxiety can influence activity in the behavioral tests, the activity of neurons in the raphe nuclei (RN), a brain region greatly involved in anxiety via the serotonergic system, was examined by staining with anti-serotonin antibodies, and increased serotonergic activity was observed. Taken together, these results suggest that ACE regulates MA levels, notably serotonin levels in the hippocampus and that RN plays an important role in ACE-induced anxiety-like behavior. - Exposure of Male Farmers and Nonfarmers to Neonicotinoid Pesticides in the South-West and Littoral Regions of Cameroon: A Comparative Study.
Faustin Pascal Tsagué Manfo, Collins Nimako, Edouard Akono Nantia, Christian Fusi Suh, Shu Policap Chenwi, Fidelis Cho-Ngwa, Paul Fewou Moundipa, Shouta M M Nakayama, Mayumi Ishizuka, Yoshinori Ikenaka
Environmental toxicology and chemistry, 43, 5, 952, 964, 2024年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Pesticides, especially the newly developed neonicotinoids, are increasingly used in many countries around the world, including Cameroon, to control pests involved in crop destruction or disease transmission. Unfortunately, the pesticides also pose tremendous environmental problems because a predominant amount of their residues enter environmental matrices to affect other nontargeted species including humans. This therefore calls for continuous biomonitoring of these insecticides in human populations. The present study sought to assess the neonicotinoid insecticide exposures in two agrarian regions of Cameroon, the South-West region and Littoral region. The study involved 188 men, including 125 farmers and 63 nonfarmers. Spot urine samples were obtained from these subjects and subjected to liquid chromatographic-tandem mass spectrometric analysis for concentrations of neonicotinoid compounds, including acetamiprid, clothianidin, dinotefuran, imidacloprid, thiacloprid, nitenpyram, thiamethoxam, and N-dm-acetamiprid. Neonicotinoid compounds were detected in all study participants, and residues of all the screened pesticides were detected among participants. N-dm-Acetamiprid and imidacloprid were the most prevalent among the subjects (100.0% and 93.1%, respectively), whereas nitenpyram was less common (3.2%). The median values of imidacloprid and total urinary neonicotinoid concentrations were elevated among farmers (0.258 vs. 0.126 µg/L and 0.829 vs. 0.312 µg/L, respectively). Altogether the findings showed that both the farmer and nonfarmer study populations of Cameroon were exposed to multiple residues of neonicotinoids, with relatively higher levels of pesticides generally recorded among farmers. Although exposure levels of the neonicotinoids were generally lower than their respective reference doses, these results warrant further research on the health risk evaluation of multiple residues of the pesticides and reinforcement of control measures to minimize the exposure risks, especially among farmers. Environ Toxicol Chem 2024;43:952-964. © 2024 SETAC. - 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), 349, 123907, 123907, 2024年04月04日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, Springer Science and Business Media LLC, 2024年03月13日
研究論文（学術雑誌） - 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, 43, 5, 943, 951, Wiley, 2024年03月05日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 484, 116847, 116847, 2024年02月07日, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - No-observed-adverse-effect-level (NOAEL) clothianidin, a neonicotinoid pesticide, impairs hippocampal memory and motor learning associated with alteration of gene expression in cerebellum.
Yukako Hara, Asuka Shoda, Sakura Yonoichi, Yuya Ishida, Midori Murata, Mako Kimura, Makiko Ito, Sarika Nunobiki, Ayano Yoshimoto, Youhei Mantani, Toshifumi Yokoyama, Tetsushi Hirano, Yoshinori Ikenaka, Yoshiaki Tabuchi, Nobuhiko Hoshi
The Journal of veterinary medical science, 86, 3, 340, 348, 2024年02月05日, ［国内誌］
英語, 研究論文（学術雑誌）, Neonicotinoid pesticides (NNs) have been associated with numerous neurobehavioral effects in rodents, raising concerns about their impact on cognitive function. Clothianidin (CLO), a type of NN, was orally administered to male mice (10 weeks old, C57BL/6N) at the no-observed-adverse-effect level (NOAEL) of 50 mg/kg/day as indicated in the pesticide risk assessment report. Behavioral tests (novel location recognition and rotarod tests) evaluated hippocampal memory and cerebellar motor learning. After each test, plasma monoamines (3-methoxytyramine, histamine, serotonin, tryptamine) were measured by LC-ESI/MS/MS (Liquid chromatography-electrospray ionization/tandem mass spectrometry), and cerebellar mRNA expression was quantified by microarray and qRT-PCR analyses. The NOAEL of CLO was found to impair hippocampal memory, leading to decreased spontaneous locomotor activity and motor function. We reported, for the first time, multiple alterations of gene expression in the cerebellum associated with motor dysfunction. - Effect of clothianidin exposure at the no-observed-adverse-effect level (NOAEL) in a mouse model of atopic dermatitis.
Yuya Ishida, Sakura Yonoichi, Yukako Hara, Asuka Shoda, Mako Kimura, Midori Murata, Makiko Ito, Sarika Nunobiki, Ayano Yoshimoto, Youhei Mantani, Toshifumi Yokoyama, Tetsushi Hirano, Eiko Matsuo, Yoshinori Ikenaka, Nobuhiko Hoshi
The Journal of veterinary medical science, 86, 3, 333, 339, 2024年02月05日, ［国内誌］
英語, 研究論文（学術雑誌）, The effects of exposure to clothianidin (CLO), a neonicotinoid pesticide (NN), on the thymus and intestinal microbiota were recently revealed. Immune cells express nicotinic acetylcholine receptors (nAChRs), an NN target, suggesting CLO may disrupt the immune system. However, the relationship between CLO and atopic dermatitis (AD) is unknown. We administered a no-adverse-effect-level (NOAEL) dose of CLO to male NC/Nga mice with induced AD and measured, at three time points, key AD symptom indicators: epidermal thickening, mast cell number, total plasma IgE, and histamine levels. CLO increased total plasma IgE levels but reduced epidermal thickening, mast cell number, and plasma histamine levels in the early stages of AD. This demonstrates for the first time that CLO exposure inhibits AD's early symptoms. - Metals and arsenic distribution in stray dogs' tissues around a lead-zinc mine in Kabwe, Zambia.
Nyein Chan Soe, Yared Beyene Yohannes, Andrew Kataba, Madalitso Tembo, John Yabe, Golden Zyambo, Kenneth Chawinga, Kaampwe Muzandu, Yoshinori Ikenaka, Mayumi Ishizuka, Shouta M M Nakayama
Environmental science and pollution research international, 31, 8, 12083, 12093, 2024年02月, ［国際誌］
英語, 研究論文（学術雑誌）, Metal contamination poses a threat to human, animal, and environmental health. The purpose of the current study was to assess the accumulation of toxic and trace metal concentrations in tissues of stray dogs in Kabwe, a town known for lead pollution due to a long history of lead and zinc mining. Brain, spleen, heart, stomach, stomach content, small intestine, kidney, liver, and bone samples were collected from 29 stray dogs (14 from locations within 3 km of the mine and 15 from sites 7 km away from the mine) after necropsy. Inductively coupled plasma mass spectrometry was used to analyze toxic metals, arsenic (As), cadmium (Cd), and lead (Pb), and trace elements, copper (Cu) and zinc (Zn). The lungs (0.117 ± 0.114 mg/kg dry weight), kidney (7.515 ± 8.830 mg/kg dry weight), and bone (41.68 ± 66.83 mg/kg dry weight) were found to have the highest concentrations of As, Cd, and Pb, respectively. In contrast, higher Cu and Zn concentrations were measured in the liver than in other tissues. In all tissues analyzed, tissues sampled from dogs near the mine had significantly higher mean concentrations of Cd and Pb than dogs far away. Neither sex nor age-related differences were observed in the distribution of metals in most tissues. There were significant associations among toxic (Pb and Cd) and trace metals (Cu and Zn). In the kidney, Cd positively correlated with Pb (ρ = 0.534) and Zn (ρ = 0.600), whereas in the liver, Cu correlated with Zn (ρ = 0.565). The current study's findings suggest that environmental pollution is still a problem in Kabwe, and environmental remediation is needed to address the pollution. - Brood patch size as a field indicator for feather mercury concentration, but not plastic ingestion, in a harvested seabird of the high Arctic: The little auk Alle alle
Mayuko Otsuki, Monica Ogawa, Watanuki Yutaka, Yoko Mitani, Mayumi Ishizuka, Yoshinori Ikenaka, Jean-Baptiste Thiebot
Polar Science, 2024年02月
研究論文（学術雑誌） - Effects of exposure to the neonicotinoid pesticide clothianidin on α-defensin secretion and gut microbiota in mice.
Sakura Yonoichi, Yukako Hara, Yuya Ishida, Asuka Shoda, Mako Kimura, Midori Murata, Sarika Nunobiki, Makiko Ito, Ayano Yoshimoto, Youhei Mantani, Toshifumi Yokoyama, Tetsushi Hirano, Yoshinori Ikenaka, Yuki Yokoi, Tokiyoshi Ayabe, Kiminori Nakamura, Nobuhiko Hoshi
The Journal of veterinary medical science, 86, 3, 277, 284, 2024年01月23日, ［国内誌］
英語, 研究論文（学術雑誌）, The mechanism by which the neonicotinoid pesticide clothianidin (CLO) disrupts the intestinal microbiota of experimental animals is unknown. We focused on α-defensins, which are regulators of the intestinal microbiota. Subchronic exposure to CLO induced dysbiosis and reduced short-chain fatty acid‒producing bacteria in the intestinal microbiota of mice. Levels of cryptdin-1 (Crp1, a major α-defensin in mice) in feces and cecal contents were lower in the CLO-exposed groups than in control. In Crp1 immunostaining, Paneth cells in the jejunum and ileum of the no-observed-adverse-effect-level CLO-exposed group showed a stronger positive signal than control, likely due to the suppression of Crp1 release. Our results showed that CLO exposure suppresses α-defensin secretion from Paneth cells as part of the mechanism underlying CLO-induced dysbiosis. - Assessment of Organohalogen Compounds Contamination in Pet Food and Associated Health Risks: A Case Study in Japan
Kei NOMIYAMA, Fuka SATO, Makoto SHIMASAKI, Hazuki MIZUKAWA, Kraisiri KHIDKHAN, Yoshinori IKENAKA, Mayumi ISHIZUKA
Environmental Monitoring and Contaminants Research, 4, 38, 54, Japan Society for Environmental Chemistry, 2024年
研究論文（学術雑誌） - Effects of exposure to the neonicotinoid pesticide clothianidin on mouse intestinal microbiota under unpredictable environmental stress.
Sakura Yonoichi, Tetsushi Hirano, Yukako Hara, Yuya Ishida, Asuka Shoda, Mako Kimura, Midori Murata, Youhei Mantani, Toshifumi Yokoyama, Yoshinori Ikenaka, Nobuhiko Hoshi
Toxicology and applied pharmacology, 482, 116795, 116795, 2023年12月29日, ［国際誌］
英語, 研究論文（学術雑誌）, Recent research has demonstrated the toxicity of neonicotinoid pesticides (NNs) in mammals through their interaction with nicotinic acetylcholine receptors (nAChRs). These effects are reported to extend to the intestinal microbiota as well. In addition, environmental stress affects the expression of nAChRs, which may alter sensitivity to NNs. In this study, we analyzed the intestinal microbiota of mice exposed to clothianidin (CLO), a type of NN, under environmental stress, and aimed to clarify the effects of such combined exposure on the intestinal microbiota. C57BL/6N male mice (9 weeks old) were subchronically administered a no-observed-adverse-effect-level (NOAEL) CLO-mixed rehydration gel for 29 days and simultaneously subjected to chronic unpredictable mild stress (CUMS). After the administration period, cecum contents were collected and analyzed by 16S rRNA sequencing for intestinal microbiota. CLO exposure alone resulted in alterations in the relative abundance of Alistipes and ASF356, which produce short-chain fatty acids. The addition of CUMS amplified these changes. On the other hand, CLO alone did not affect the relative abundance of Lactobacillus, but the abundance decreased when CUMS was added. This study revealed that the combined exposure to CLO and stress not only amplifies their individual effects on intestinal microbiota but also demonstrates combined and multifaceted toxicities. - An adverse outcome pathway-based approach to assess the neurotoxicity by combined exposure to current-use pesticides
Tetsushi Hirano, Yoshinori Ikenaka, Kei Nomiyama, Masato Honda, Nobuo Suzuki, Nobuhiko Hoshi, Yoshiaki Tabuchi
Toxicology, 500, 153687, 153687, Elsevier BV, 2023年11月, ［国際誌］
英語, 研究論文（学術雑誌）, Exposure to multiple pesticides in daily life has become an important public health concern. However, the combined effects of pesticide mixtures have not been fully elucidated by the conventional toxicological testing used for individual chemicals. Grouping of chemicals by mode of action using common key events (KEs) in the adverse outcome pathway (AOP) as endpoints could be applied for efficient risk assessment of combined exposure to multiple chemicals. The purpose of this study was to investigate whether exposure to multiple pesticides has synergistic neurotoxic effects on mammalian nervous systems. According to the AOP-based approach, we evaluated the effects of 10 current-use pesticides (4 neonicotinoids, 4 pyrethroids and 2 phenylpyrazoles) on the common KEs in AOPs for neurotoxicity, such as KEs involving mitochondrial and proteolytic functions, in a mammalian neuronal cell model. Our data showed that several pyrethroids and phenylpyrazoles partly shared the effects on several common KEs, including decreases in mitochondrial membrane potential and proteasome activity and increases in autophagy activity. Furthermore, we also found that combined exposure to a type-I pyrethroid permethrin or a type-II pyrethroid deltamethrin and the phenylpyrazole fipronil decreased the cell viability and the benchmark doses much more than either single exposure, indicating that the pair exhibited synergistic effects, since the combination indexes were less than 1. These findings revealed that novel pairs of different classes of pesticides with similar effects on common KEs exhibited synergistic neurotoxicity and provide new insights into the risk assessment of combined exposure to multiple chemicals. - 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, 341, 122837, 122837, Elsevier BV, 2023年11月, ［国際誌］
英語, 研究論文（学術雑誌）, Anticoagulant rodenticides (ARs) are used to control pest rodent species but can result in secondary poisoning of non-target animals, especially raptors. In the present study, differences in AR sensitivity among avian species were evaluated by comparing in vivo warfarin pharmacokinetics and effects, measuring cytochrome P450s (CYPs) expression involved in AR metabolism, and conducting in vitro inhibition assays of the AR target enzyme Vitamin K 2,3-epoxide reductase (VKOR). Oral administration of warfarin at 4 mg/kg body weight did not prolong prothrombin time in chickens (Gallus gallus), rock pigeons (Columba livia), or Eastern buzzards (Buteo japonicus). Rock pigeons and buzzards exhibited shorter plasma half-life of warfarin compared to chickens. For the metabolite analysis, 4'-hydroxywarfarin was predominantly detected in all birds, while 10-hydroxywarfarin was only found in pigeons and raptors, indicating interspecific differences in AR metabolism among birds likely due to differential expression of CYP enzymes involved in the metabolism of ARs and variation of VKOR activities among these avian species. The present findings, and results of our earlier investigations, demonstrate pronounced differences in AR sensitivity and pharmacokinetics among bird species, and in particular raptors. While ecological risk assessment and mitigation efforts for ARs have been extensive, AR exposure and adverse effects in predatory and scavenging wildlife continues. Toxicokinetic and toxicodynamic data will assist in such risk assessments and mitigation efforts. - 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, 85, 12, 1355, 1365, 2023年10月31日, ［国内誌］
英語, 研究論文（学術雑誌）, 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. - Transgenerational effects of developmental neurotoxicity induced by exposure to a no-observed-adverse-effect level (NOAEL) of neonicotinoid pesticide clothianidin.
Asuka Shoda, Midori Murata, Mako Kimura, Yukako Hara, Sakura Yonoichi, Yuya Ishida, Youhei Mantani, Toshifumi Yokoyama, Tetsushi Hirano, Yoshinori Ikenaka, Nobuhiko Hoshi
The Journal of veterinary medical science, 85, 9, 1023, 1029, 2023年08月04日, ［国内誌］
英語, 研究論文（学術雑誌）, Neonicotinoid pesticides (NNs) transfer rapidly from mother to offspring, which exhibit neurobehavioral effects. However, no studies have investigated NNs' transgenerational effects. We exposed F0 generation mice (mothers) to a no-observed-adverse-effect level (NOAEL) of clothianidin (CLO) during gestation and lactation, and examined the adult neurobehavioral effects of three generations of offspring (F1, F2, F3). F1 had lower birth weight, decreased locomotor activity, and increased anxiety-like behavior. In F2, body weight was affected, and there was a decreasing trend in locomotor activity and an increasing trend in anxiety-like behavior. In F3, locomotor activity tended to increase. Thus, even when only the mothers were exposed, the effects of CLOs were still observed in F1, F2, and F3 but the effects became smaller. - 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, 103, 5, 1129, 1143, 2023年07月27日, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - フィプロニル代謝物が引き起こすミクログリアの活性化がエクソソームを介してニューロンに及ぼす影響
平野 哲史, 池中 良徳, 星 信彦, 田渕 圭章
The Journal of Toxicological Sciences, 48, Suppl., S144, S145, (一社)日本毒性学会, 2023年06月
日本語 - コンパニオンアニマルのPFAS汚染:イヌ・ネコの種差要因と汚染の地域差
佐藤 愛佳, 佐藤 楓夏, 水川 葉月, 池中 良徳, 田上 瑠美, 横山 望, 滝口 満喜, 中津 賞, 野見山 桂
環境化学物質3学会合同大会要旨集, 2回, 305, 306, (一社)日本環境化学会・日本環境毒性学会・環境ホルモン学会, 2023年05月
日本語 - フィプロニル代謝物によるミクログリアの活性化およびエクソソーム分泌を介したニューロンへの作用
平野 哲史, 池中 良徳, 星 信彦, 田渕 圭章
環境化学物質3学会合同大会要旨集, 2回, 655, 655, (一社)日本環境化学会・日本環境毒性学会・環境ホルモン学会, 2023年05月
日本語 - 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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 tissue distribution, metabolism, effects on brain catecholamines, and environmental exposure of frogs to neonicotinoid insecticides.
So Shinya, Fumiya Nishibe, Yared Beyene Yohannes, Mayumi Ishizuka, Shouta M Nakayama, Yoshinori Ikenaka
Aquatic toxicology (Amsterdam, Netherlands), 257, 106437, 106437, 2023年04月, ［国際誌］
英語, 研究論文（学術雑誌）, Pesticide exposure is considered to be one important factor responsible for declining amphibian populations worldwide. The usage of neonicotinoid insecticides (NNIs) has markedly increased in recent years, and there are concerns regarding the effects of NNI-induced toxicity on the development and behavior of amphibians. However, there have been few reports on the metabolism, distribution, and neurotoxicity of NNIs in amphibians. In this study, we exposed the Western clawed frog (Silurana tropicalis) to clothianidin (CLT) in water. After 24 h of exposure, the highest concentrations were detected in the skin, indicating that frogs are at a high risk of absorbing CLT through their skin along with water. Excretion of CLT was estimated based on the concentrations of CLT metabolites in the water until 48 h of exposure. The findings showed that frogs had higher CLT metabolic ability than zebrafish. Serotonin levels in the brain were lower in the high-concentration CLT exposure group than in the control group, although the difference was not statistically significant. This suggested that catecholamine-related effects of CLT on the brain cannot be disregarded. In addition, quantitative analyses of NNI residue in wild frogs, soil, and water in agricultural areas in Hokkaido, Japan, were performed and four NNIs were detected. These results indicated the possible risk of NNI-induced toxicity in frogs. This is the first report of the characteristics of tissue distribution and metabolism of NNIs in frogs, which may facilitate the design of appropriate conservation programs for amphibians. - 鳥類におけるバロキサビルマルボキシルの安全性の検討
三木 万梨子, 尾原 涼, 西村 享平, 岡 良子, 宍戸 貴雄, 福島 民雄, 吉本 淳, 中山 翔太, 木村 亨史, 池中 良徳, 小笠原 浩平, 齊藤 慶輔, 日尾野 隆大, 磯田 典和, 迫田 義博
日本野生動物医学会誌, 27, Suppl., 176, 177, 日本野生動物医学会, 2023年03月
日本語 - 前思春期のビスフェノール類曝露と性・ステロイドホルモン値との関連 北海道スタディ
池田 敦子, 山口 健史, アイツバマイ ゆふ, 池中 良徳, ケテマ・ラヘルメスフィ, 曾 怡, 中村 明枝, 橘田 岳也, 今 雅史, 篠原 信雄, 真部 淳, 宮下 ちひろ, コバチ・アドリアン, 岸 玲子
日本衛生学雑誌, 78, Suppl., S181, S181, (一社)日本衛生学会, 2023年03月
日本語 - 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - Developmental stage-specific exposure and neurotoxicity evaluation of low-dose clothianidin during neuronal circuit formation.
Asuka Shoda, Midori Murata, Mako Kimura, Yukako Hara, Sakura Yonoichi, Yuya Ishida, Youhei Mantani, Toshifumi Yokoyama, Tetsushi Hirano, Yoshinori Ikenaka, Yoshiaki Tabuchi, Nobuhiko Hoshi
The Journal of veterinary medical science, 85, 4, 486, 496, 2023年03月01日, ［国内誌］
英語, 研究論文（学術雑誌）, Neonicotinoid pesticides (NN) were recently reported to exhibit adverse effects in higher vertebrates. Moreover, NNs are routinely transferred from mother to offspring, raising concerns about their effects on future generations. The fetal and neonatal periods are the most critical to the formation of neural circuits in the brain through neurogenesis and differentiation, neuronal migration, axon guidance, and synaptogenesis. NN exposure throughout the fetal and neonatal periods was found to affect the neurobehavior of the offspring, but the stage-specific neurobehavioral effects are unclear. We exposed fetal and neonatal mice to a no-observed-adverse-effect level (NOAEL) of clothianidin (CLO) for 4 days during each of four developmental stages: neurite proliferation and differentiation (fetal days 9-12, CLO-1), neurite outgrowth (fetal days 15-18, CLO-2), synapse formation and astrocyte differentiation (days 1-4 after birth, CLO-3), and synapse remodeling (days 11-14 after birth, CLO-4). CLO's neurobehavioral effects were evaluated in juveniles and adults, revealing that CLO-1 and CLO-2 caused behavioral abnormalities in adult mice. CLO-3 significantly increased locomotor activity and decreased juvenile neurons in the hippocampal dentate gyrus in adulthood. Comprehensive gene analysis of CLO-3 revealed high expression of genes related to neurite outgrowth and axonal branching in the hippocampus in juveniles and adults. These results revealed developmental stage-specific effects of a NOAEL of CLO in the fetal and neonatal periods, suggesting that the susceptibility of the fetus and neonate to CLO varies by developmental stage. - Neurotoxicity and behavioral disorders induced in mice by acute exposure to the diamide insecticide chlorantraniliprole.
Mako Kimura, Asuka Shoda, Midori Murata, Yukako Hara, Sakura Yonoichi, Yuya Ishida, Youhei Mantani, Toshifumi Yokoyama, Tetsushi Hirano, Yoshinori Ikenaka, Nobuhiko Hoshi
The Journal of veterinary medical science, 85, 4, 497, 506, 2023年02月28日, ［国内誌］
英語, 研究論文（学術雑誌）, Diamide insecticides activate ryanodine receptors expressed in lepidopteran skeletal muscle and promote Ca2+ release in the sarcoplasmic reticulum, causing abnormal contractions and paralysis, leading to death of the pest. Although they had been thought not to act on nontarget organisms, including mammals, adverse effects on vertebrates were recently reported, raising concerns about their safety in humans. We investigated the neurotoxicity of the acute no-observed-adverse-effect level of chlorantraniliprole (CAP), a diamide insecticide, in mice using clothianidin (CLO), a neonicotinoid insecticide, as a positive control. The CLO-administered group showed decreased locomotor activities, increased anxiety-like behaviors, and abnormal human-audible vocalizations, while the CAP-administered group showed anxiety-like behaviors but no change in locomotor activities. The CAP-administered group had greater numbers of c-fos‒immunoreactive cells in the hippocampal dentate gyrus, and similar to the results in a CLO-administered group in our previous study. Blood corticosterone levels increased in the CLO-administered group but did not change in the CAP-administered group. Additionally, CAP was found to decreased 3-Methoxytyramine and histamine in mice at the time to maximum concentration. These results suggest that CAP-administered mice are less vulnerable to stress than CLO-administered mice, and the first evidence that CAP exposure increases neuronal activity and induces anxiety-like behavior as well as neurotransmitter disturbances in mammals. - 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, ［国内誌］
英語, 研究論文（学術雑誌）, 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. - Status Report on Neonicotinoid Pollution in Japan: Emphasis on Human, Animal, and Environmental Health
NIMAKO Collins, NAKAYAMA Shouta M. M., YOHANNES Yared Beyene, IKENAKA Yoshinori, ISHIZUKA Mayumi
Environmental Monitoring and Contaminants Research, 3, 69, 91, Japan Society for Environmental Chemistry, 2023年
英語, Neonicotinoid insecticides are exclusively used for insect control in many parts of the globe. Since early 1992, various neonicotinoid active compounds have been used for pest control in Japan. At present, all seven major neonicotinoid active compounds, imidacloprid, acetamiprid, dinotefuran, clothianidin, thiamethoxam, thiacloprid, and nitenpyram, are used in Japan, and the total shipment amount of these chemicals in the country was estimated 337.9 tons in 2022. Due to the massive neonicotinoid application in Japan, concerns have been raised about their potential infiltrations into nontarget ecosystems and their effects on human and ecological species. These concerns have inspired several studies, extensively investigating the environmental contamination levels and exposure tendencies in humans and several other invertebrate species. The current status report harmonized the up-to-date data on neonicotinoids in Japan and identified the incoherencies or knowledge gaps existing in the neonicotinoid literature reported in Japan. The report further summarized extensive neonicotinoid publications globally to illustrate the distributions of various neonicotinoid compounds in agricultural soils and surface waters and their exposures in humans and nontarget animal species. This report represents a few perspectives with detailed data from Japan into perspective. - 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
Pesticide biochemistry and physiology, 199, 105767, 105767, Elsevier BV, 2023年, ［国際誌］
英語, 研究論文（学術雑誌）, The Bonin Archipelago is a United Nations Educational, Scientific and Cultural Organization's World Natural Heritage Site in Japan with a unique ecosystem; however, the invasive rodents preying on endemic species have been a significant concern. The anticoagulant rodenticide, diphacinone, sprayed by the Ministry of the Environment, has succeeded; however, its repeated use leads to rodenticide resistance. This study evaluated the sensitivity by in vivo pharmacokinetics/pharmacodynamics (PK/PD) analysis and physiologically-based pharmacokinetic modeling to diphacinone in black rats (Rattus rattus) captured on the Bonin Archipelago in February 2022. The Bonin rats exhibited prolonged coagulation time after diphacinone administration. They recovered earlier than susceptible black rats, indicating that Bonin rats were less susceptible, though there were no genetic mutations in Vkorc1, the target enzyme of diphacinone. After the administration of diphacinone, hepatic expression levels of Fsp1, identified as the vitamin K reductase, was decreased, however, the Bonin rats exhibited the most minor suppression. The PK analysis showed that the excretion capacity of the Bonin rats was lower than that of the resistant black rats. In the PBPK modeling, the resistant black rats showed higher clearance than the Bonin and susceptible black rats due to high hepatic metabolic capacity. The Bonin rats demonstrated slow absorption and relatively low clearance. This study highlighted the reduced rodenticide-sensitive tendency of wild black rats in the Bonin Archipelago at an in vivo phenotype level. At the same time, they do not have known rodenticide resistance mechanisms, such as hepatic metabolic enhancement or Vkorc1 mutations. It is crucial to monitor the biological levels to evaluate rodenticide sensitivity accurately. - Biological effects related to exposure to polychlorinated biphenyl (PCB) and decabromodiphenyl ether (BDE-209) on cats
Khidkhan K, Mizukawa H, Ikenaka Y, Nakayama SMM, Nomiyama K, Yokoyama N, Ichii O, Takiguchi M, Tanabe S, Ishizuka M
PLOS ONE, 18, 1, e0277689, 2023年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - 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, MDPI AG, 2022年12月13日, ［査読有り］, ［招待有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - 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, Springer Science and Business Media LLC, 2022年12月, ［国際誌］
英語, 研究論文（学術雑誌）, Abstract
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. - Thiamethoxam intoxication due to occupational inhalational exposure.
Toshinori Nishizawa, Yoshinori Ikenaka, Go Ichikawa, Tomohiro Taguchi
BMJ case reports, 15, 11, 2022年11月29日, ［国際誌］
英語, 研究論文（学術雑誌）, Neonicotinoid is a new class of systemic insecticides that are selectively toxic to insects. However, cases of human toxicity have been reported. A man in his 60s, who worked as a pest control operator (which required the use of thiamethoxam), presented with fever and headache. We investigated the levels of thiamethoxam and clothianidin in the blood and urine. Our results suggested that chronic thiamethoxam intoxication was caused by occupational inhalation exposure and environmental pollution. After cessation of insecticide use, the patient remained asymptomatic but had persistent oral dysesthesia and postural finger tremor, even at undetectable levels of thiamethoxam and clothianidin. This case report is the first to describe human thiamethoxam intoxication after occupational inhalation exposure. When similar symptoms are encountered and a history of insecticide use is confirmed, clinicians should consider the diagnosis of neonicotinoid intoxication. - 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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, ［国内誌］
英語, 研究論文（学術雑誌）, 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. - Quantitative elucidation of the transfer of the neonicotinoid pesticide clothianidin to the breast milk in mice.
Asuka Shoda, Misaki Nishi, Midori Murata, Youhei Mantani, Toshifumi Yokoyama, Tetsushi Hirano, Yoshinori Ikenaka, Nobuhiko Hoshi
Toxicology letters, 373, 33, 40, 2022年10月31日, ［国際誌］
英語, 研究論文（学術雑誌）, Neonicotinoid pesticides (NNs) have been reported to have neurobehavioral effects on offspring after fetal and lactational exposure. In this study, clothianidin (CLO), an NN, was administered orally as a single dose (6.5mg/kg: 1/10 of the no-observed-adverse-effect level in the current Pesticide Evaluation Report) to 10-day post-partum ICR mice, and CLO and its metabolites were quantified using liquid chromatography-electrospray ionization/tandem mass spectrometry (LC-ESI/MS/MS) after collecting maternal breast milk and blood samples over time (1, 3, 6, 9, 12, and 24h after administration). CLO and its metabolite desmethyl-CLO (dm-CLO) were detected in the breast milk at 1h after the administration, and their concentrations were significantly higher than those in blood at all time points. The concentrations of CLO and dm-CLO in the breast milk were at their highest levels at 1 and 3h, respectively, and then decreased over time to become almost undetectable at 24h after the administration. These results show that CLO is metabolized in the mother's body and is rapidly transferred to and concentrated in the breast milk. Since CLO concentrations in breast milk are higher than those in the blood, there is concern about the effects of CLO during lactation. - 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - Does Moringa Oleifera affect element accumulation patterns and lead toxicity in Sprague–Dawley rats?
Hokuto Nakata, Shouta M.M. Nakayama, Andrew Kataba, Haruya Toyomaki, Rio Doya, Yared Beyene Yohannes, Yoshinori Ikenaka, Mayumi Ishizuka
Journal of Functional Foods, 97, 105242, Elsevier BV, 2022年10月 - 胎児期フタル酸エステル類曝露による思春期発来への影響 北海道スタディ
山口 健史, 池田 敦子, アイツバマイ ゆふ, 宮下 ちひろ, 池中 良徳, 中村 明枝, 今 雅史, 藤谷 倫子, 原田 浩二, 岸 玲子
DOHaD研究, 10, 2, 46, 46, (一社)日本DOHaD学会, 2022年10月
日本語 - Serum steroid profiling of hepatocellular carcinoma associated with hyperadrenocorticism in dogs: A preliminary study
Thandar Oo, Noboru Sasaki, Yoshinori Ikenaka, Takahiro Ichise, Noriyuki Nagata, Nozomu Yokoyama, Kazuyoshi Sasaoka, Keitaro Morishita, Kensuke Nakamura, Mitsuyoshi Takiguchi
Frontiers in Veterinary Science, 9, 1014792, 1014792, Frontiers Media SA, 2022年09月28日, ［国際誌］
英語, 研究論文（学術雑誌）, Background
Hepatocellular carcinoma (HCC) is one of the most common primary liver tumors in humans and dogs. Excessive adrenocortical hormone exposure may cause steroid hepatopathy, which may develop into HCC. In our previous study, hyperadrenocorticism (HAC) was a highly concurrent disease in dogs with HCC. Therefore, this study hypothesized that adrenal steroid alterations might be involved in hepatocarcinogenesis and aimed to specify the relationship between HAC and HCC in dogs.
Materials and methods
This study included 46 dogs brought to the Hokkaido University Veterinary Teaching Hospital between March 2019 and December 2020. Owners gave their signed consent for blood collection on their first visit. A total of 19 steroids (14 steroids and 5 metabolites) in the baseline serum of 15 dogs with HCC, 15 dogs with HAC, and 10 dogs with both diseases were quantitatively measured using the developed liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) method.
Results
In each group, 11 steroids were detected higher than 50%. The detection rate of steroid hormones did not significantly differ between the groups (p > 0.05). Principle component analysis (PCA) showed that the steroid profiles of the three groups were comparable. Median steroid hormone concentrations were not significantly different between the study diseases (p > 0.05).
Conclusion
The developed LC/MS/MS was useful for measuring steroid hormones. Although it was clear that HAC was concurrent in dogs with HCC, none of the serum steroids was suggested to be involved in HCC. - 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, 2022年09月28日, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - バロキサビルマルボキシルのニワトリへの4週間反復経口投与による安全性評価
三木 万梨子, 尾原 涼, 西村 享平, 岡 良子, 宍戸 貴雄, 福島 民雄, 吉本 淳, 中山 翔太, 木村 享史, 池中 良徳, 日尾野 隆大, 磯田 典和, 迫田 義博
日本獣医学会学術集会講演要旨集, 165回, [DV1A, 08], (公社)日本獣医学会, 2022年09月
日本語 - 胎子授乳期ネオニコチノイド系農薬曝露が海馬記憶と運動学習に及ぼす次世代影響
原 悠佳子, 世ノ一 さくら, 石田 祐也, 正田 明日香, 村田 碧, 木村 真子, 万谷 洋平, 横山 俊史, 平野 哲史, 池中 良徳, 星 伸彦
日本獣医学会学術集会講演要旨集, 165回, [J1P, 05], (公社)日本獣医学会, 2022年09月
日本語 - 環境ストレス負荷下におけるネオニコチノイド系農薬曝露が腸内細菌叢に及ぼす影響
世ノ一 さくら, 石田 祐也, 原 悠佳子, 木村 真子, 正田 明日香, 村田 碧, 万谷 洋平, 横山 俊史, 平野 哲史, 池中 良徳, 星 信彦
日本獣医学会学術集会講演要旨集, 165回, [J1P, 06], (公社)日本獣医学会, 2022年09月
日本語 - 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, 1, 12, 2022年09月, ［国際誌］
英語, 研究論文（学術雑誌） - Toxicokinetic analysis of the anticoagulant rodenticides warfarin & 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, Elsevier BV, 2022年09月, ［国際誌］
英語, 研究論文（学術雑誌）, Anticoagulant rodenticides have been widely used to eliminate wild rodents, which as invasive species on remote islands can disturb ecosystems. Since rodenticides can cause wildlife poisoning, it is necessary to evaluate the sensitivity of local mammals and birds to the poisons to ensure the rodenticides are used effectively. The Bonin Islands are an archipelago located 1000 km southeast of the Japanese mainland and are famous for the unique ecosystems. Here the first-generation anticoagulant rodenticide diphacinone has been used against introduced black rats (Rattus rattus). The only land mammal native to the archipelago is the Bonin fruit bat (Pteropus pselaphon), but little is known regarding its sensitivity to rodenticides. In this study, the Egyptian fruit bats (Rousettus aegyptiacus) was used as a model animal for in vivo pharmacokinetics and pharmacodynamics analysis and in vitro enzyme kinetics using their hepatic microsomal fractions. The structure of vitamin K epoxide reductase (VKORC1), the target protein of the rodenticide in the Bonin fruit bat, was predicted from its genome and its binding affinity to rodenticides was evaluated. The Egyptian fruit bats excreted diphacinone slowly and showed similar sensitivity to rats. In contrast, they excreted warfarin, another first-generation rodenticide, faster than rats and recovered from the toxic effect faster. An in silico binding study also indicated that the VKORC1 of fruit bats is relatively tolerant to warfarin, but binds strongly to diphacinone. These results suggest that even chemicals with the same mode of action display different sensitivities in different species: fruit bat species are relatively resistant to warfarin, but vulnerable to diphacinone. - Drought altered trophic dynamics of an important natural saline lake: A stable isotope approach.
Lizaan de Necker, Luc Brendonck, Ruan Gerber, Pieter Lemmens, David X Soto, Yoshinori Ikenaka, Mayumi Ishizuka, Victor Wepener, Nico J Smit
The Science of the total environment, 834, 155338, 155338, 2022年08月15日, ［国際誌］
英語, 研究論文（学術雑誌）, Climate change and associated droughts threaten the ecology and resilience of natural saline lakes globally. There is a distinct lack of research regarding their ecological response to climatic events in the Global South. This region is predicted to experience climatic events such as El Niño-Southern Oscillation (ENSO) more often and with greater severity with the potential to alter the structure and functioning of aquatic ecosystems significantly. From 2015 to 2016 South Africa experienced one of the most severe country-wide droughts as a result of a strong ENSO event. Our study aimed to investigate the effect of this supra-seasonal drought on the trophic structure of fish communities in a naturally saline shallow lake of a Ramsar wetland using stable isotope techniques. Fishes and potential basal sources were collected from the lake, during predrought conditions in 2010 and after severe drought (recovery phase; 2017). The δ13C and δ15N values of food web elements were determined and analysed using Bayesian mixing models and Bayesian Laymen metrics to establish the proportional contribution of C3 and C4 basal sources to the fish (consumer) diets, and examine the fish community in terms of isotopic niche and trophic structure, respectively. Fish consumers relied predominantly on C3 basal sources in the predrought and shifted to greater reliance on C4 basal sources, decreased isotopic niche space use and a reduction in trophic length in the recovery phase. Drought altered the type and abundance of the basal sources available by limiting sources to those that are more drought-tolerant, reducing the trophic pathways of the food web with no significant alterations in the fish community. These results demonstrate the resilience and biological plasticity of Lake Nyamithi and its aquatic fauna, highlighting the importance of freshwater inflow to saline lakes with alterations thereof posing a significant threat to their continued functioning. - 造影CT検査後に非心原性肺水腫を呈した褐色細胞腫を疑う犬の1例
吉田 紫乃, 田村 純, 永田 矩之, 大山 紀彦, 新坊 弦也, 池中 良徳, 滝口 満喜
北海道獣医師会雑誌, 66, 8, 289, 289, (公社)北海道獣医師会, 2022年08月
日本語 - 犬尿中コルチゾール/クレアチニン比の基準値の確立とクッシング症候群の診断への応用
永田 矩之, 澤村 飛龍, 五日市 大介, 森下 啓太郎, 細谷 謙次, 横山 望, 笹岡 一慶, 佐々木 東, 中村 健介, 池中 良徳, 滝口 満喜
北海道獣医師会雑誌, 66, 8, 286, 286, (公社)北海道獣医師会, 2022年08月
日本語 - 造影CT検査後に非心原性肺水腫を呈した褐色細胞腫を疑う犬の1例
吉田 紫乃, 田村 純, 永田 矩之, 大山 紀彦, 新坊 弦也, 池中 良徳, 滝口 満喜
北海道獣医師会雑誌, 66, 8, 289, 289, (公社)北海道獣医師会, 2022年08月
日本語 - 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, 850, 157833, 157833, Elsevier BV, 2022年08月, ［国際誌］
英語, 研究論文（学術雑誌）, Lead (Pb) pollution and human exposure to Pb, is an important issue for the international community to address being associated with 0.90 million deaths from long-term effects. The Republic of Zambia is a typical mineral resource-rich country, with long-standing mining and smelting activities of metals including Pb in several parts of the country. This narrative review provides a comprehensive overview of previous papers that have assessed human exposure to Pb and related health effects in Zambia. Environmental remediation methods that should be applied locally, ways to reduce Pb exposure of the population, and issues that need to be addressed by various sectors are discussed. Environmental remediation methods using locally available and affordable materials are needed to ensure both sustainable industrial activities and pollution prevention. In the Zambian mining towns, including Kabwe, various research activities have been conducted, including environmental monitoring, human biomonitoring and health impact assessments. The town of Kabwe, which was one of Zambia's largest Pb mining area in the 20th century, continues to have formal and informal Pb-related industries and is known as one of the most polluted areas in the world. For example, despite the World Health Organization asserting that "For an individual with a blood Pb concentration ≥ 5 μg/dL, appropriate action should be taken to terminate exposure", there are reports of blood Pb levels in Kabwe children exceeding 100 μg/dL. While Pb pollution is a global issue, not many places have such continuous and comprehensive research has been conducted, and there is much to be learned from the knowledge accumulated in these areas. Because the high levels of Pb accumulation in humans and the adverse health effects were clarified, we consider that it is important to combine mining activities, which are a key industry, with measures to prevent environmental pollution. - 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - Estimation of the Effects of Neonicotinoid Insecticides on Wild Raccoon, Procyon lotor , in Hokkaido, Japan: Urinary Concentrations and Hepatic Metabolic Capability 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, Wiley, 2022年06月09日, ［国際誌］
英語, 研究論文（学術雑誌）, Toxicological effects of neonicotinoid insecticides (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 NNI-induced toxicities on wildlife because they live near agricultural fields and eat crops treated with NNIs. The objective of the present study was to estimate the effects of NNI 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 one 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 seven 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 liquid chromatography-electrospray ionization-tandem mass spectrometry and compared with those in rats. Raccoons showed much lower metabolic ability; the maximum velocity/Michaelis-Menten constant (Vmax /Km ) values for raccoons were one-tenth to one-third of those for rats. For the first time, we show that wild raccoons could be frequently exposed to NNIs in the environment, and that the cytochrome P450-dependent metabolism of NNIs in the livers of raccoons might be low. Our results contribute to a better understanding of the effects of NNIs on raccoons, leading to better conservation efforts for wild mammals. Environ Toxicol Chem 2022;41:1865-1874. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. - 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - 日本のペット動物における有機フッ素化合物の汚染実態
野見山 桂, 佐藤 楓夏, 水川 葉月, 池中 良徳, 田上 瑠美, 横山 望, 滝口 満喜
環境化学物質3学会合同大会要旨集, 2022年, 195, 196, (一社)日本環境化学会・日本環境毒性学会・環境ホルモン学会, 2022年06月
日本語 - 神経毒性のAOPにおける共通Key Eventを指標とした農薬類の複合影響評価
平野 哲史, 池中 良徳, 星 信彦, 田渕 圭章
環境化学物質3学会合同大会要旨集, 2022年, 332, 332, (一社)日本環境化学会・日本環境毒性学会・環境ホルモン学会, 2022年06月
日本語 - Urinary corticoid to creatinine ratios using IMMULITE 2000 XPi for diagnosis of canine hypercortisolism.
Noriyuki Nagata, Hiryu Sawamura, Keitaro Morishita, Kenji Hosoya, Nozomu Yokoyama, Kazuyoshi Sasaoka, Noboru Sasaki, Kensuke Nakamura, Yoshinori Ikenaka, Mitsuyoshi Takiguchi
The Journal of veterinary medical science, 84, 7, 954, 959, 2022年05月27日, ［国内誌］
英語, 研究論文（学術雑誌）, The urinary corticoid to creatinine ratio (UCCR) is one of the most commonly used screening tests for canine hypercortisolism (HC). In this study, a reference interval was established for UCCR using IMMULITE 2000 XPi, the latest chemiluminescence enzyme immunoassay. The diagnostic performance of this method for UCCR in canine HC was also evaluated. The median UCCR was 1.06 × 10-5 (range: 0.28-2.49) for 58 healthy dogs, and an upper reference limit of 1.98 × 10-5 (90% confidence interval: 1.76-2.15) was determined. The median UCCR in the 12 dogs with HC (7.38 × 10-5, range 1.86-29.98) was significantly higher than that in the 16 dogs with mimic-HC (1.59 × 10-5, range 0.47-3.42, P<0.001). The area under the curve for UCCR to differentiate HC dogs from mimic-HC dogs was 0.971, with a sensitivity of 91.7% and specificity of 100% when the cut-off value was set at 3.77 × 10-5. The UCCR of 16 paired urine samples collected at home and in hospital showed that the UCCR of samples collected in the hospital was significantly higher than that of samples collected at home (mean difference 3.30 × 10-5, 95% confidence interval: 0.70-5.90, P=0.001). In summary, we established the upper reference limit for UCCR using IMMULITE 2000 XPi in dogs and confirmed that UCCR is a useful diagnostic test for HC in dogs if urine samples are collected at home. - 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - 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, e0265225, Public Library of Science (PLoS), 2022年03月21日, ［国際誌］
英語, 研究論文（学術雑誌）, 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 5ʹ-GCAGC-3ʹ, 5ʹ-GCTGC-3ʹ, and 5ʹ-GCGGC-3ʹ, but not of 5ʹ-GCCGC-3ʹ. This resulted in the production of fully-methylated 5ʹ-GCWGC-3ʹ and hemi-methylated 5ʹ-GCSGC-3ʹ. 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. - 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
研究論文（学術雑誌） - 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 Part - C: Toxicology and Pharmacology, 252, 109215, 109215, 2022年02月, ［国際誌］
英語, 研究論文（学術雑誌） - 土地利用方法に着目した野生トカゲの重金属汚染バイオモニタリング；ザンビア共和国の鉱山跡地を例として
銅谷 理緒, 中山 翔太, 中田 北斗, 近藤 充希, Golden ZYAMBO, Kaampwe MUZANDU, John YABE, 池中 良徳, 石塚 真由美
日本毒性学会学術年会, 49.1, P-133, 日本毒性学会, 2022年
日本語, In Kabwe town in the Republic of Zambia, heavy metal pollution has been widespread due to lead and zinc mining activities since the early 20th, and it continues even after the official cessation of industrial operation in 1994. In addition to soil, high concentrations of lead have been detected in humans, domestic animals, and wild rodents (Yabe et al. 2015, Nakata et al. 2017, Nakayama et al. 2011).
We employed a species of wild lizards (Trachylepis wahlbergii) as a target organism for biomonitoring focusing on land use patterns. This species was considered to be suitable because they live in relatively small home ranges, they only prey on insects, and they are widely distributed from residential areas to grasslands.
An initial field survey was conducted in 2017 to collect the lizards and soil of their habitat. Liver and other organs were collected from 224 lizards. Metal analysis of lizard and soil samples was performed by ICP-MS after acid digestion with a microwave system. The highest concentration in the liver was 200μg/g, which is much higher than the previous result in the same area using other animal species. Also, biological concentrations were relatively high in places near the mine and areas without vegetation. A follow-up survey was conducted in 2021 to further investigate the species-specificity of accumulation pattern, chronological shift, and relationship of these points with changes in land use pattern. The analytical results of 112 lizards are presented together with environmental parameters and geographical analysis. - Assessing the Net Benefits of Organic Farming interventions in Ecosystem Preservation against Emerging Pesticides
Collins NIMAKO, Anri HIRAI, Takahiro ICHISE, Shouta M.M. NAKAYAMA, Mayumi ISHIZUKA, Yoshinori IKENAKA
日本毒性学会学術年会, 49.1, P-108, 日本毒性学会, 2022年
日本語, Organic farming practices are generally considered potential countermeasures against pesticide exposure in human populations. However, little is known if current organic interventional measures adopted in Japan can mitigate neonicotinoid (NNI) exposures or otherwise. The current validates the efficacies of organic dietary interventions in ameliorating NNIs exposures within the Japanese population. Firstly, 103 Japanese volunteers were recruited and fed strictly with either organic diets for 5 or 30 days or with conventional diets. Then the exposure rates of 8 NNIs were determined in the population, by LC-MS/MS analysis. After analysis, 8 NNIs were detected in the target population; but the detection rates were far lower in the organic diet consumers compared to conventional diet consumers. The organic dietary intervention drastically reduced the cumulative levels and the daily intake rates of NNIs in the Japanese population. Subsequently, the residual levels of NNIs were determined in organic and conventional green tea leaves produced in Japan. Seven NNIs compounds and one NNI metabolite were detected in tea leaves cultivated by strict organic farming methods. However, the detection rates of NNIs were relatively lower in organic tea leaves than conventional tea leaves. Moreover, the daily exposure rates of NNIs through green tea consumption were far lower for organic tea leaves than conventional tea leaves. These findings ultimately show that the adoption of organic farming interventions may offer optimum ameliorative outcomes on NNI exposure rates Japanese population. - Elucidation of the neurological effects of clothianidin exposure at the no-observed-adverse-effect level (NOAEL) using two-photon microscopy <i>in vivo</i> imaging
Misaki NISHI, Shouta SUGIO, Tetsushi HIRANO, Daisuke KATO, Hiroaki WAKE, Asuka SHODA, Midori MURATA, Yoshinori IKENAKA, Yoshiaki TABUCHI, Youhei MANTANI, Toshifumi YOKOYAMA, Nobuhiko HOSHI
Journal of Veterinary Medical Science, 84, 4, 585, 592, Japanese Society of Veterinary Science, 2022年, ［国内誌］
英語, 研究論文（学術雑誌）, Neonicotinoid pesticides (NNs) cause behavioral abnormalities in mammals, raising concerns about their effects on neural circuit activity. We herein examined the neurological effects of the NN clothianidin (CLO) by in vivo Ca2+ imaging using two-photon microscopy. Mice were fed the no-observed-adverse-effect-level (NOAEL) dose of CLO for 2 weeks and their neuronal activity in the primary somatosensory cortex (S1) was observed weekly for 2 weeks. CLO exposure caused a sustained influx of Ca2+ in neurons in the S1 2/3 layers, indicating hyperactivation of neurons. In addition, microarray gene expression analysis suggested the induction of neuroinflammation and changes in synaptic activity. These results demonstrate that exposure to the NOAEL dose of CLO can overactivate neurons and disrupt neuronal homeostasis. - Safety Assessment of Ultrasound-Assisted Intravesical Chemotherapy in Normal Dogs: A Pilot Study.
Noboru Sasaki, Yoshinori Ikenaka, Keisuke Aoshima, Teiichiro Aoyagi, Nobuki Kudo, Kensuke Nakamura, Mitsuyoshi Takiguchi
Frontiers in pharmacology, 13, 837754, 837754, 2022年, ［国際誌］
英語, 研究論文（学術雑誌）, Intravesical chemotherapy after transurethral resection is a treatment option in patients with non-muscle invasive bladder cancer. The efficacy of intravesical chemotherapy is determined by the cellular uptake of intravesical drugs. Therefore, drug delivery technologies in the urinary bladder are promising tools for enhancing the efficacy of intravesical chemotherapy. Ultrasound-triggered microbubble cavitation may enhance the permeability of the urothelium, and thus may have potential as a drug delivery technology in the urinary bladder. Meanwhile, the enhanced permeability may increase systemic absorption of intravesical drugs, which may increase the adverse effects of the drug. The aim of this preliminary safety study was to assess the systemic absorption of an intravesical drug that was delivered by ultrasound-triggered microbubble cavitation in the urinary bladder of normal dogs. Pirarubicin, a derivative of doxorubicin, and an ultrasound contrast agent (Sonazoid) microbubbles were administered in the urinary bladder. Ultrasound (transmitting frequency 5 MHz; pulse duration 0.44 μsec; pulse repetition frequency 7.7 kHz; peak negative pressure -1.2 MPa) was exposed to the bladder using a diagnostic ultrasound probe (PLT-704SBT). The combination of ultrasound and microbubbles did not increase the plasma concentration of intravesical pirarubicin. In addition, hematoxylin and eosin staining showed that the combination of ultrasound and microbubble did not cause observable damages to the urothelium. Tissue pirarubicin concentration in the sonicated region was higher than that of the non-sonicated region in two of three dogs. The results of this pilot study demonstrate the safety of the combination of intravesical pirarubicin and ultrasound-triggered microbubble cavitation, that is, ultrasound-assisted intravesical chemotherapy. - 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01日, ［国際誌］
英語, 研究論文（学術雑誌） - Urinary concentrations of neonicotinoid insecticides were related to renal tubular dysfunction and neuropsychological complaints in Dry-zone of Sri Lanka
Kumiko Taira, Tomonori Kawakami, Sujithra Kaushaliya Weragoda, H. M.Ayala S. Herath, Yoshinori Ikenaka, Kazutoshi Fujioka, Madhubhani Hemachandra, Nirmalie Pallewatta, Yoshiko Aoyama, Mayumi Ishizuka, Jean Marc Bonmatin, Makiko Komori
Scientific Reports, 11, 1, 22484, 22484, 2021年12月, ［国際誌］
英語, 研究論文（学術雑誌） - 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10月01日, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - 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09月17日, ［国内誌］
英語, 研究論文（学術雑誌）, 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. - 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09月16日, ［国内誌］
英語, 研究論文（学術雑誌）, 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. - Neurotoxicity of a pyrethroid pesticide deltamethrin is associated with the imbalance in proteolytic systems caused by mitophagy activation and proteasome inhibition.
Tetsushi Hirano, Nihei Suzuki, Yoshinori Ikenaka, Nobuhiko Hoshi, Yoshiaki Tabuchi
Toxicology and applied pharmacology, 430, 115723, 115723, 2021年09月11日, ［国際誌］
英語, 研究論文（学術雑誌）, Pyrethroids are one of the most commonly used classes of synthetic pesticides in the world. Recent laboratory and epidemiological evidence suggested that pyrethroids have potential adverse effects in the mammalian brain; however, the underlying mechanisms of the neurotoxic effects of pyrethroids have not been fully elucidated. In the present study, we investigated the mechanisms of effects of a type II pyrethroid deltamethrin (DM) in a neuronal cell model focusing on the proteolytic function, including autophagy and the ubiquitin-proteasome system. We confirmed that a micromolar concentration of DM dose-dependently decreased the cell viability and induced apoptotic cell death. Our results showed that DM enhanced autophagy in association with an accumulation of autophagosomes and increase in the levels of autophagy markers LC3-II/LC3-I ratio and p62 which were much elevated in the presence of lysosomal inhibitors bafilomycin A1 and chloroquine. We also found that DM caused a dysfunction of mitochondria with a decrease of mitochondrial membrane potential and mitochondrial DNA copy number as well as colocalization with autophagosomes. Moreover, a decrease in the activities of three major proteasomal enzymes and an accumulation of ubiquitinated proteins were observed by the exposure to DM. Transcriptome analysis revealed that up-regulated genes supported the activation of autophagy with induction of cellular stress responses including oxidative stress and endoplasmic reticulum stress, while down-regulated genes related to the cell cycle and DNA replication. These findings provide novel insights into the neurotoxicity of DM which underlie the imbalance in proteolytic function caused by mitophagy activation and proteasome inhibition. - ゼブラフィッシュを用いたネオニコチノイド系農薬の体内動態と発達神経毒性の解明
池本 秀樹, 沖澤 優花, 川合 佑典, 一瀬 貴大, 池中 良徳, 久保田 彰
環境ホルモン学会研究発表会要旨集, 23回, 40, 40, 環境ホルモン学会(日本内分泌撹乱化学物質学会), 2021年09月
日本語 - 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], (公社)日本獣医学会, 2021年09月
英語 - 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - 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, 2021年08月28日, ［国際誌］
英語, 研究論文（学術雑誌） - Analysis of lead distribution in avian organs by LA-ICP-MS: Study of experimentally lead-exposed ducks and kites.
Ryouta Torimoto, Chihiro Ishii, Hiroshi Sato, Keisuke Saito, Yukiko Watanabe, Kohei Ogasawara, Ayano Kubota, Takehisa Matsukawa, Kazuhito Yokoyama, Atsushi Kobayashi, Takashi Kimura, Shouta M M Nakayama, Yoshinori Ikenaka, Mayumi Ishizuka
Environmental pollution (Barking, Essex : 1987), 283, 117086, 117086, 2021年08月15日, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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, (一社)日本毒性学会, 2021年07月
英語 - Bioaccumulation of DDT and other organochlorine pesticides in amphibians from two conservation areas within malaria risk regions of South Africa.
Nico J Wolmarans, Lieven Bervoets, Ruan Gerber, Yared Beyene Yohannes, Shouta Mm Nakayama, Yoshinori Ikenaka, Mayumi Ishizuka, Patrick Meire, Nico J Smit, Victor Wepener
Chemosphere, 274, 129956, 129956, 2021年07月, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - Characteristics of neonicotinoid and metabolite residues in Taiwanese tea leaves.
Tzu-Hsuen Yuan, Meng-Ting Yu, Yoshinori Ikenaka, Yi-Hsuan Chen, Shoji F Nakayama, Chang-Chuan Chan
Journal of the science of food and agriculture, 102, 1, 341, 349, 2021年06月10日, ［国際誌］
英語, 研究論文（学術雑誌） - Prostaglandin-related immune suppression in cattle
Y. Sajiki, S. Konnai, Y. Ikenaka, T. Okagawa, N. Maekawa, C. Logullo, I. da Silva Vaz, S. Murata, K. Ohashi
Veterinary Immunology and Immunopathology, 236, 110238, 110238, Elsevier BV, 2021年06月
研究論文（学術雑誌） - The effects of fipronil on emotional and cognitive behaviors in mammals.
Tomohiro Suzuki, Anri Hirai, Kraisiri Khidkhan, Collins Nimako, Takahiro Ichise, Kazuki Takeda, Hazuki Mizukawa, Shouta M M Nakayama, Kei Nomiyama, Nobuhiko Hoshi, Mizuki Maeda, Tetsushi Hirano, Kazuyoshi Sasaoka, Noboru Sasaki, Mitsuyoshi Takiguchi, Mayumi Ishizuka, Yoshinori Ikenaka
Pesticide biochemistry and physiology, 175, 104847, 104847, 2021年06月, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - Aging-related changes in the sensitivity of behavioral effects of the neonicotinoid pesticide clothianidin in male mice.
Tetsushi Hirano, Yuka Miyata, Shizuka Kubo, Shuji Ohno, Kanoko Onaru, Mizuki Maeda, Sayaka Kitauchi, Misaki Nishi, Yoshiaki Tabuchi, Yoshinori Ikenaka, Takahiro Ichise, Shouta M M Nakayama, Mayumi Ishizuka, Koji Arizono, Keisuke Takahashi, Keisuke Kato, Youhei Mantani, Toshifumi Yokoyama, Nobuhiko Hoshi
Toxicology letters, 342, 95, 103, 2021年05月15日, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - Assessment of LeadCare® II analysis for testing of a wide range of blood lead levels in comparison with ICP-MS analysis.
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, 271, 129832, 129832, 2021年05月, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - Effects of in utero and lactational exposure to the no-observed-adverse-effect level (NOAEL) dose of the neonicotinoid clothianidin on the reproductive organs of female mice.
Sayaka Kitauchi, Mizuki Maeda, Tetsushi Hirano, Yoshinori Ikenaka, Misaki Nishi, Asuka Shoda, Midori Murata, Youhei Mantani, Toshifumi Yokoyama, Yoshiaki Tabuchi, Nobuhiko Hoshi
The Journal of veterinary medical science, 83, 4, 746, 753, 2021年04月24日, ［国内誌］
英語, 研究論文（学術雑誌）, Recently, developmental exposure to clothianidin (CLO) has been shown to cause reproductive toxicity in male mice, but the effects in female mice remain to be clarified. Pregnant C57BL/6N mice were given a no-observed-adverse-effect-level (NOAEL) dose of CLO until weaning. We then examined ovaries of 3- or 10-week-old female offspring. In the CLO-administered group, morphological changes, a decrease in the immunoreactivity of the antioxidant enzyme glutathione peroxidase 4 (GPx4), and activation of genes in the steroid hormone biosynthesis pathway were observed in 3-week-old mice, and decreases of GPx4 immunoreactivity, 17OH-progesterone and corticosterone levels were observed in 10-week-old mice, along with high rates of infanticide and severe neglect, providing new evidence that developmental exposure to CLO affects juvenile and adult mice differently. - Urinary free metanephrines measurement in dogs with adrenal gland diseases using a new simple liquid chromatography tandem mass spectrometry method.
Noboru Sasaki, Yoshinori Ikenaka, Yumiko Inoue, Takahiro Ichise, Noriyuki Nagata, Mayumi Ishizuka, Syouta Mm Nakayama, Kensuke Nakamura, Mitsuyoshi Takiguchi
The Journal of veterinary medical science, 83, 4, 648, 655, 2021年04月09日, ［国内誌］
英語, 研究論文（学術雑誌）, Measurement of urinary metanephrines in spot samples is used for the diagnosis of canine pheochromocytoma (PC). We describe a simple analytical method based on liquid chromatography tandem mass spectrometry (LC-MS/MS) for measuring free metanephrine (MN) and normetanephrine (NMN) in spot urine samples. Using the developed method, we evaluated the stability of urinary free-MN and free-NMN at various storing conditions. In addition, we assessed the feasibility of urinary free-MN and -NMN measurement for diagnosing PC. Urine samples were mixed with stable isotope internal standards and thereafter purified by ultrafiltration. The purified samples were analyzed by LC-MS/MS in the multiple reaction monitoring mode after separation on a multimode octa decyl silyl column. The coefficient of variation of free-MN and -NMN measurement was 7.6% and 5.5%, respectively. The linearity range was 0.5-10 µg/l for both analytes. Degradation was less than 10% for both analytes under any of the storage conditions. The median free-NMN ratio to creatinine of 9 PC dogs (595, range 144-47,961) was significantly higher (P<0.05) than that of 13 dogs with hypercortisolism (125, range 52-224) or 15 healthy dogs (85, range 50-117). The developed method is simple and may not require acidification of spot urine. The results of this preliminary retrospective study suggest that the measurement of urinary free metanephrines is a promising tool for diagnosing canine PC. - Chronic low-dose exposure to imidacloprid potentiates high fat diet-mediated liver steatosis in C57BL/6J male mice.
Collins Nimako, Yoshinori Ikenaka, Yuko Okamatsu-Ogura, Jussiaea V Bariuan, Atsushi Kobayashi, Ryo Yamazaki, Kumiko Taira, Nobuhiko Hoshi, Tetsushi Hirano, Shouta M M Nakayama, Mayumi Ishizuka
The Journal of veterinary medical science, 83, 3, 487, 500, 2021年04月03日, ［国内誌］
英語, 研究論文（学術雑誌）, 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. - Fetal and lactational exposure to the no-observed-adverse-effect level (NOAEL) dose of the neonicotinoid pesticide clothianidin inhibits neurogenesis and induces different behavioral abnormalities at the developmental stages in male mice.
Mizuki Maeda, Sayaka Kitauchi, Tetsushi Hirano, Yoshinori Ikenaka, Misaki Nishi, Asuka Shoda, Midori Murata, Youhei Mantani, Yoshiaki Tabuchi, Toshifumi Yokoyama, Nobuhiko Hoshi
The Journal of veterinary medical science, 83, 3, 542, 548, 2021年04月03日, ［国内誌］
英語, 研究論文（学術雑誌）, Recently, it has been reported that neonicotinoid pesticides (NNs) are transferred from mother to child and are assumed to affect the next generation, but the behavioral effects of NN exposure at different developmental stages have not been investigated. We exposed mice to no-observed-adverse-effect level (NOAEL) doses of clothianidin (CLO) during the fetal and lactational period, and then evaluated the neurobehavioral effects in juvenile and adult mice. Significant increases in anxiety-like behavior and locomotor activity were observed in juveniles and adults, respectively, and neuronal activity and neurogenesis in the hippocampal dentate gyrus were affected in both stages. These results suggest that fetal and lactational exposure to CLO may inhibit neurogenesis and cause different behavioral abnormalities at different developmental stages. - 超音波で生体の壁を超える 超音波と気泡を併用する膀胱内注入療法の犬における安全性検討
佐々木 東, 青柳 貞一郎, 池中 良徳, 工藤 信樹, 中村 健介, 滝口 満喜
超音波医学, 48, Suppl., S195, S195, (公社)日本超音波医学会, 2021年04月
日本語 - Sensitivity of turtles to anticoagulant rodenticides: Risk assessment for green sea turtles (Chelonia mydas) in the Ogasawara Islands and comparison of warfarin sensitivity among turtle species.
Yoshiya Yamamura, Kazuki Takeda, Yusuke K Kawai, Yoshinori Ikenaka, Chiyo Kitayama, Satomi Kondo, Chiho Kezuka, Mari Taniguchi, Mayumi Ishizuka, Shouta M M Nakayama
Aquatic toxicology (Amsterdam, Netherlands), 233, 105792, 105792, 2021年04月, ［国際誌］
英語, 研究論文（学術雑誌） - The VKORC1 ER-luminal loop mutation (Leu76Pro) leads to a significant resistance to warfarin in black rats (Rattus rattus).
Kazuki Takeda, Yoshinori Ikenaka, Denis Fourches, Kazuyuki D Tanaka, Shouta M M Nakayama, Dhoha Triki, Xinhao Li, Manabu Igarashi, Tsutomu Tanikawa, Mayumi Ishizuka
Pesticide biochemistry and physiology, 173, 104774, 104774, 2021年03月, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - Estimation of the feeding record of pregnant Antarctic minke whales (Balaenoptera bonaerensis) using carbon and nitrogen stable isotope analysis of baleen plates
Mayuka Uchida, Ippei Suzuki, Keizo Ito, Mayumi Ishizuka, Yoshinori Ikenaka, Shouta M. M. Nakayama, Tsutomu Tamura, Kenji Konishi, Takeharu Bando, Yoko Mitani
POLAR BIOLOGY, 44, 3, 621, 629, 2021年02月
英語, 研究論文（学術雑誌） - 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
英語, 研究論文（学術雑誌） - 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - Tick saliva-induced programmed death-1 and PD-ligand 1 and its related host immunosuppression.
Yamato Sajiki, Satoru Konnai, Yoshinori Ikenaka, Kevin Christian Montecillo Gulay, Atsushi Kobayashi, Luís Fernando Parizi, Benvindo Capela João, Kei Watari, Sotaro Fujisawa, Tomohiro Okagawa, Naoya Maekawa, Carlos Logullo, Itabajara da Silva Vaz Jr, Shiro Murata, Kazuhiko Ohashi
Scientific reports, 11, 1, 1063, 1063, 2021年01月13日, ［国際誌］
英語, 研究論文（学術雑誌）, The tick Rhipicephalus microplus is a harmful parasite of cattle that causes considerable economic losses to the cattle breeding industry. Although R. microplus saliva (Rm-saliva) contains several immunosuppressants, any association between Rm-saliva and the expression of immunoinhibitory molecules, such as programmed death (PD)-1 and PD-ligand 1 (PD-L1), has not been described. In this study, flow cytometric analyses revealed that Rm-saliva upregulated PD-1 expression in T cells and PD-L1 expression in CD14+ and CD11c+ cells in cattle. Additionally, Rm-saliva decreased CD69 expression in T cells and Th1 cytokine production from peripheral blood mononuclear cells. Furthermore, PD-L1 blockade increased IFN-γ production in the presence of Rm-saliva, suggesting that Rm-saliva suppresses Th1 responses via the PD-1/PD-L1 pathway. To reveal the upregulation mechanism of PD-1/PD-L1 by Rm-saliva, we analyzed the function of prostaglandin E2 (PGE2), which is known as an inducer of PD-L1 expression, in Rm-saliva. We found that Rm-saliva contained a high concentration of PGE2, and PGE2 treatment induced PD-L1 expression in CD14+ cells in vitro. Immunohistochemical analyses revealed that PGE2 and PD-L1 expression was upregulated in tick-attached skin in cattle. These data suggest that PGE2 in Rm-saliva has the potential to induce the expression of immunoinhibitory molecules in host immune cells. - Simultaneous Detection Technique and Chronic Low-dose Accumulation Trends of Imidacloprid and its Metabolites in Tissues of C57BL/6J Mice
Collins NIMAKO, Yoshinori IKENAKA, Osei AKOTO, Kazutoshi FUJIOKA, Kumiko TAIRA, Koji ARIZONO, Keisuke KATO, Keisuke TAKAHASHI, Shouta M.M. NAKAYAMA, Takahiro ICHISE, Mayumi ISHIZUKA
日本毒性学会学術年会, 48.1, P-154E, 日本毒性学会, 2021年
日本語, The present study aimed to (i) develop a sensitive LC-MS/MS-based technique for simultaneous detection and quantification of Imidacloprid (IMI) and its metabolites in tissue specimens, and to (ii) determine the specific bioaccumulation trends of the IMI compounds in organs of C57BL/6J male mice; after exposure to 0.6 mg/kg bw/day of IMI (10% of NOAEL) 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, LOQs ≤ 1.43 ng/mL and R2 ≥ 0.99) and precise (RSDs ≤ 20%) for routine analysis of IMI and seven of its metabolites in in blood and various tissues of mice. Upon biodistribution analysis, IMI and five of its metabolites were detected in various organs within mice. Blood, liver, mesenteric white adipose tissue and pancreas mainly accumulated IMI-olefin; brain, testis, inguinal white adipose tissue and gonadal white adipose tissue mainly accumulated IMI, whereas the kidney mainly accumulated 4-hydroxy-IMI. The N-desnitro-IMI metabolite showed unique accumulation in brain and testis by recording brain-blood and testis-blood detection ratios of 8.4 and 7.6, respectively. Cumulative levels of the six detected IMI compounds (Σ6 IMI compounds) were found in the decreasing order; blood > testis > iWAT > kidney > brain > gWAT > mWAT > pancreas > liver. The current study provides essential data needed for effective mechanistic elucidation of compound-specific adverse outcomes associated with chronic exposures to IMI in mammalian species. - 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
日本語, 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。 - タンパク質分解系を指標としたピレスロイド系農薬デルタメトリンによる神経毒性メカニズムの解析
平野 哲史, 鈴木 二平, 池中 良徳, 星 信彦, 田渕 圭章
日本毒性学会学術年会, 48, P, 2E, 日本毒性学会, 2021年
日本語,【背景・目的】農薬等の化学物質曝露は、異常タンパク質の蓄積やミトコンドリアの機能異常を原因とする神経変性疾患のリスク要因となる可能性が指摘されている。本研究では、細胞内のタンパク質分解を司るオートファジーおよびユビキチンプロテアソーム系に着目し、ピレスロイド系農薬デルタメトリン（DM）による神経毒性メカニズムの一端を解明することを目的とした。
【方法】Neuro2a細胞を1–100 µMのDMに曝露し、wst-8アッセイおよびフローサイトメーターを用いて生細胞数およびアポトーシス細胞数を測定した。ウェスタンブロットおよび免疫染色により各種オートファジーマーカー（LC3、p62）、ミトコンドリアマーカー（TOM20、UQCRC1）の発現量および細胞内局在を解析した。加えて、JC-10および定量的PCRを用いてミトコンドリアの機能および量的影響を評価し、ユビキチン化タンパク質量およびプロテアソーム活性の測定を行った。
【結果・考察】DM曝露により濃度依存的なLC3-IIおよびp62発現量の上昇がみられ、30 µM以上の濃度ではアポトーシス細胞数の増加が観察された。一方で、DM曝露によりUQCRC1発現およびmtDNA量が低下し、膜電位の脱分極を伴うミトコンドリア傷害が誘導された。加えて、DM曝露群の細胞質中においてドット上に凝集した各種マーカーが共局在することから、ミトコンドリアが取り込んだオートファゴソームが蓄積することが明らかとなった。DMによりユビキチン化タンパク質量は増加し、各種プロテアソーム活性は低下した。以上の結果から、DM曝露時においてはプロテアソーム活性の低下に伴い、傷害されたミトコンドリアを基質とするマイトファジーの活性が上昇していることが示され、両タンパク質分解系の不均衡状態がアポトーシス誘導に関与することが初めて明らかとなった。
- 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - Interspecies differences in cytochrome P450-mediated metabolism of neonicotinoids among cats, dogs, rats, and humans.
Kraisiri Khidkhan, Yoshinori Ikenaka, Takahiro Ichise, Shouta M M Nakayama, Hazuki Mizukawa, Kei Nomiyama, Hisato Iwata, Koji Arizono, Keisuke Takahashi, Keisuke Kato, Mayumi Ishizuka
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 239, 108898, 108898, 2021年01月, ［国際誌］
英語, 研究論文（学術雑誌）, 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - 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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - Resolving the twin human and environmental health hazards of a plant-based diet.
Kris A G Wyckhuys, Alexandre Aebi, Maarten F I J Bijleveld van Lexmond, Carlos R Bojaca, Jean-Marc Bonmatin, Lorenzo Furlan, Jairo A Guerrero, Trinh V Mai, Hoi V Pham, Francisco Sanchez-Bayo, Yoshinori Ikenaka
Environment international, 144, 106081, 106081, 2020年11月, ［国際誌］
英語, 研究論文（学術雑誌）, Food can be health-giving. A global transition towards plant-based diets may equally help curb carbon emissions, slow land-system change and conserve finite resources. Yet, projected benefits of such 'planetary health' diets imperfectly capture the environmental or societal health outcomes tied to food production. Here, we examine pesticide-related hazards of fruit and vegetable consumption, and list proven management alternatives per commodity, geography and chemical compound. Across countries, pesticide use in these alleged healthful foods is extensive with up to 97% food items containing residues and up to 42% posing dietary risks to consumers. Multiple residues are present in 70-92% of US- and China-grown stone fruit while 58% US cauliflower is tainted with neonicotinoid insecticides. Science-based alternatives and decision-support frameworks can help food producers reduce risks and potential harm by deliberately abstaining from pesticide use. As such, opportunities abound to advance 'win-win' diets that simultaneously nurture human health and conserve global biodiversity. - 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - Levels of DDTs and other organochlorine pesticides in healthy wild Nile crocodiles (Crocodylus niloticus) from a flagship conservation area.
Ruan Gerber, Hindrik Bouwman, Danny Govender, Mayumi Ishizuka, Yoshinori Ikenaka, Yared B Yohannes, Nico J Smit, Victor Wepener
Chemosphere, 264, Pt 1, 128368, 128368, 2020年09月18日, ［国際誌］
英語, 研究論文（学術雑誌）, Mass Nile crocodile (Crocodylus niloticus) deaths in Africa's premier conservation area, the Kruger National Park (KNP), prompted numerous studies to determine possible causes of the sudden die-offs. The majority highlighted the involvement of the anthropocene to crocodile mass mortalities. One of the potential causative agents was identified as legacy compounds such as organochlorine pesticides (OCPs) present in the various aquatic ecosystems of the KNP. Thus, this study aimed to quantify OCP levels in wild crocodiles from the aquatic systems associated with the KNP. As part of a larger study, muscle tissue samples were collected from tails of 12 wild crocodiles. Results indicated that eight of the 19 OCPs analysed for were quantifiable. These included DDTs (2130-167968 ng/g lw), chlordanes (BD - 7583 ng/g lw) and cyclodeines (BD - 872 ng/g lw). Measured concentrations indicated spatial- and sex-related differences in accumulation patterns. DDT and its metabolites, paricularly p,p'-DDE accumulated to the highest concentrations of the OCP groups. Levels of the different groups of OCPs were the highest recorded in recent history from any crocodilian tissue. The different measured OCP residues were between 2.5 and 120 times higher than levels reported in literature, depending on the compound. These results are of ecotoxicological significance and have several management implications. In view of individuals being sampled from a conservation area it emphasizes the fact that pollutants know no boundaries and that premier conservation areas such as the world renowned KNP may be some of the most contaminated areas of the world. - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - 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］, ［国内誌］
英語, 研究論文（学術雑誌）, 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. - 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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - Altered hepatic cytochrome P450 expression in cats after chronic exposure to decabromodiphenyl ether (BDE-209).
Kraisiri Khidkhan, Hazuki Mizukawa, Yoshinori Ikenaka, Shouta M M Nakayama, Kei Nomiyama, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Shinsuke Tanabe, Mayumi Ishizuka
The Journal of veterinary medical science, 82, 7, 978, 982, 2020年07月31日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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. - 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, (一社)日本毒性学会, 2020年06月
日本語 - 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, (一社)日本毒性学会, 2020年06月
日本語 - 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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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 Vmax and Km values than those of DTT; however, there was no significant difference in their Vmax/Km and IC50 for warfarin. - Using Stable Î13C and Î15N Isotopes to Assess Foodweb Structures in an African Subtropical Temporary Pool
L. De Necker, A. Manfrin, Y. Ikenaka, M. Ishizuka, L. Brendonck, J. H.J. Van Vuren, B. Sures, V. Wepener, N. J. Smit
African Zoology, 55, 1, 79, 92, 2020年05月
研究論文（学術雑誌） - 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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - 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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - Combined exposure to dinotefuran and chronic mild stress counteracts the change of the emotional and monoaminergic neuronal activity induced by either exposure singly despite corticosterone elevation in mice.
Tadashi Takada, Naoki Yoneda, Tetsushi Hirano, Kanoko Onaru, Youhei Mantani, Toshifumi Yokoyama, Hiroshi Kitagawa, Yoshiaki Tabuchi, Collins Nimako, Mayumi Ishizuka, Yoshinori Ikenaka, Nobuhiko Hoshi
The Journal of veterinary medical science, 82, 3, 350, 359, 2020年03月24日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Dinotefuran (DIN) belongs to the neonicotinoids (NNs), a class of globally applied pesticides originally developed to exhibit selective toxicity in insects. However, several reports have suggested that NNs also exert neurotoxic effects in mammals. We previously demonstrated neurobehavioral effects of DIN on mice under non-stressful conditions. For further toxicity assessments in the present study, we investigated the effects of DIN on mice exposed to stressful conditions. After subacutely administering a no-observed-effect-level (NOEL) dose of DIN and/or chronic unpredictable mild stress (CUMS) to mice, we conducted three behavioral tests (i.e., open field test [OFT], tail suspension test [TST] and forced swimming test [FST]). In addition, serotonin (5-HT) and tryptophan hydroxylase 2 (TPH2) of the dorsal raphe nuclei (DRN) and median raphe nuclei (MRN) and tyrosine hydroxylase (TH) of the ventral tegmental area and substantia nigra (SN) were evaluated immunohistochemically. A NOEL dose of DIN or CUMS alone increased of the total distance in OFT, decreased or increased the immobility time in TST or FST, respectively, and increased the positive intensity of 5-HT and TPH2 in the DRN/MRN, and TH in the SN. These changes were suppressed under the conditions of combined exposure to DIN and CUMS, though the blood corticosterone level was increased depending on the blood DIN values and the presence of CUMS. The present study suggests the multifaceted toxicity of the neurotoxin DIN. - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - 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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - 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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - クロチアニジンおよびその代謝産物の母子間移行における組織分布・蓄積性の定量的解明
大野 周嗣, 大成 果乃子, 久保 静花, 平野 哲史, 万谷 洋平, 横山 俊史, 石塚 真由美, 池中 良徳, 星 信彦
環境ホルモン学会研究発表会要旨集, 22回, 66, 66, 環境ホルモン学会(日本内分泌撹乱化学物質学会), 2019年12月
日本語 - 低用量クロチアニジンによる情動変容への加齢の影響評価
宮田 結佳, 久保 静花, 大野 周嗣, 大成 果乃子, 前田 瑞稀, 中西 怜稀, 平野 哲史, 万谷 洋平, 横山 俊史, 石塚 真由美, 池中 良徳, 星 信彦
環境ホルモン学会研究発表会要旨集, 22回, 68, 68, 環境ホルモン学会(日本内分泌撹乱化学物質学会), 2019年12月
日本語 - 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, 環境ホルモン学会(日本内分泌撹乱化学物質学会), 2019年12月
日本語 - Tissue distribution and characterization of feline cytochrome P450 genes related to polychlorinated biphenyl exposure.
Kraisiri Khidkhan, Hazuki Mizukawa, Yoshinori Ikenaka, Shouta M M Nakayama, Kei Nomiyama, Nozomu Yokoyama, Osamu Ichii, Wageh Sobhy Darwish, Mitsuyoshi Takiguchi, Shinsuke Tanabe, Mayumi Ishizuka
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 226, 108613, 108613, 2019年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - Growth and neurite stimulating effects of the neonicotinoid pesticide clothianidin on human neuroblastoma SH-SY5Y cells.
Tetsushi Hirano, Satsuki Minagawa, Yukihiro Furusawa, Tatsuya Yunoki, Yoshinori Ikenaka, Toshifumi Yokoyama, Nobuhiko Hoshi, Yoshiaki Tabuchi
Toxicology and applied pharmacology, 383, 114777, 114777, 2019年11月15日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Neonicotinoids are one of most widely used pesticides targeting nicotinic acetylcholine receptors (nAChRs) of insects. Recent epidemiological evidence revealed increasing amounts of neonicotinoids detected in human samples, raising the critical question of whether neonicotinoids affect human health. We investigated the effects of a neonicotinoid pesticide clothianidin (CTD) on human neuroblastoma SH-SY5Y cells as in vitro models of human neuronal cells. Cellular and functional effects of micromolar doses of CTD were evaluated by changes in cell growth, intracellular signaling activities and gene expression profiles. We examined further the effects of CTD on neuronal differentiation by measuring neurite outgrowth. Exposure to CTD (1-100 μM) significantly increased the number of cells within 24 h of culture. The nAChRs antagonists, mecamylamine and SR16584, inhibited this effect, suggesting human α3β4 nAChRs could be targets of neonicotinoids. We observed a transient intracellular calcium influx and increased phosphorylation of extracellular signal-regulated kinase 1/2 shortly after exposure to CTD. Transcriptome analysis revealed that CTD down-regulated genes involved in neuronal function (e.g., formation of filopodia and calcium ion influx) and morphology (e.g., axon guidance signaling and cytoskeleton signaling); these changes were reflected by a finding of increased neurite length during neuronal differentiation. These findings provide novel insight into the potential risks of neonicotinoids to the human nervous system. - 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］, ［国内誌］
英語, 研究論文（学術雑誌）, 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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, Elsevier BV, 2019年10月
研究論文（学術雑誌） - 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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - GABA攪乱物質フィプロニルがマウスの情動行動に及ぼす影響
前田 瑞稀, 大成 果乃子, 大野 周嗣, 久保 静花, 杉田 晄佑, 宮田 結佳, 北内 佐也加, 西 美咲, 高田 匡, 平野 哲史, 万谷 洋平, 横山 俊史, 池中 良徳, 星 信彦
日本獣医学会学術集会講演要旨集, 162回, 504, 504, (公社)日本獣医学会, 2019年08月
日本語 - Syntheses of 4-OH and 5-OH Imidacloprids
Takahashi Keisuke, Tsurumi Tatsuya, Inami Moe, Li Zui, Kusakabe Taichi, Kikkawa Shoko, Azumaya Isao, Tominaga Nobuaki, Ikenaka Yoshinori, Arizono Koji, Kato Keisuke
CHEMISTRYSELECT, 4, 24, 7343, 7345, 2019年06月28日, ［査読有り］
研究論文（学術雑誌） - 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
日本語 - ヒト神経芽細胞腫におけるネオニコチノイド系農薬のシグナル毒性的影響評価と作用機序の解析
平野 哲史, 皆川 沙月, 古澤 之裕, 柚木 達也, 池中 良徳, 横山 俊史, 星 信彦, 田渕 圭章
The Journal of Toxicological Sciences, 44, Suppl., S280, S280, (一社)日本毒性学会, 2019年06月
日本語 - 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, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - Baseline bio-accumulation concentrations and resulting oxidative stress in Synodontis zambezensis after an acute laboratory exposure to 4,4'-DDT.
C M Volschenk, Y Ikenaka, Y B Yohannes, S M Nakayama, M Ishizuka, E Smit, J H J van Vuren, R Greenfield
Pesticide biochemistry and physiology, 156, 44, 55, 2019年05月, ［国際誌］
英語, 研究論文（学術雑誌）, The use of 1,1'-(2,2,2-Trichloro-1,1-ethanediyl)bis(4-chlorobenzene) (DDT) as a pesticide for the control of insects vectors responsible for the spread of many life threatening diseases was officially banned in 1972 by the United States Environmental Protection Agency (USEPA). It was banned throughout the world, in most developed countries, because of the toxic effects it causes in wildlife, including birds and fish. However, DDT is still used in approximately 43 African countries, including South Africa, to control the spread of malaria. The lipophilic nature of DDT and therefore its persistence in the environment makes it extremely important for laboratory based studies to be conducted in an effort to evaluate the accumulation potential and possible physiological effects of DDT in aquatic organisms under controlled conditions. The aim of this study was to establish baseline bioaccumulation concentrations within Synodontis zambezensis following an acute exposure to 4,4'-DDT. The three metabolites analysed were 4,4'-DDE, 4,4'-DDD and 4,4'-DDT. None of the 2,4'-isomers were analysed in this study since the acute exposure used a solution of 98.7% pure 4,4'-DDT (Sigma-Aldrich PESTANAL®, Analytical Standard, CAS-No 50-29-3, Batch number SZBE057XV) and not a mixture of 4,4'-DDT and 2,4'-DDT as found in technical grade DDT. Soxhlet extraction of tissue samples and liquid/liquid extraction of water samples followed by analysis through Gas-chromatography mass-spectrophotometry was completed. Mean 4,4'-DDE, 4,4'-DDD and 4,4'-DDT concentrations ranged from 15.34 ng/g to 45.34 ng/g, 28.16 ng/g to 63.25 ng/g and 28.64 ng/g to 96.21 ng/g respectively. All of the accumulated concentrations fell within environmentally relevant concentrations with no input through the food web. The accumulated concentrations of 4,4'-DDT and its three metabolites resulted in oxidative stress responses within the gills and the liver tissue of S. zambezensis. Significant differences (p ≤ .05) were observed between malondialdehyde (MDA) and reduced glutathione (GSH) within the liver and in superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) in the gills. - Functional and molecular characterization of UDP-glucuronosyltransferase 2 family in cynomolgus macaques.
Uno Y, Takahira R, Murayama N, Onozeki S, Kawamura S, Uehara S, Ikenaka Y, Ishizuka M, Ikushiro S, Yamazaki H
Biochemical pharmacology, 163, 335, 344, 2019年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌） - Characterization of function and genetic feature of UDP-glucuronosyltransferase in avian species.
Kawai YK, Shinya S, Ikenaka Y, Saengtienchai A, Kondo T, Darwish WS, Nakayama SMM, Mizukawa H, Ishizuka M
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 217, 5, 14, 2019年03月, ［査読有り］, ［国際誌］
英語 - 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］, ［国内誌］
英語, 研究論文（学術雑誌） - ヒト神経芽細胞腫におけるネオニコチノイド系農薬のシグナル毒性的影響評価と作用機序の解析
平野 哲史, 皆川 沙月, 古澤 之裕, 柚木 達也, 池中 良徳, 横山 俊史, 星 信彦, 田渕 圭章
日本毒性学会学術年会, 46, P, 88E, 日本毒性学会, 2019年
日本語,【背景・目的】1990年代以降に農薬登録されたネオニコチノイドは昆虫のニコチン性アセチルコリン受容体（nAChRs）に対するアゴニスト作用を示す新規農薬であるが、動物実験により哺乳類nAChRsを介して不測の影響を及ぼす例が報告されている。また、国内外における本農薬使用量の増加に伴い、ヒト尿からの検出率および検出量が急増している一方で、ヒトnAChRsに対する作用については十分に検証されていない。本研究では、ネオニコチノイド系農薬の1種クロチアニジン（CTD）がヒト神経芽細胞腫に及ぼすシグナル毒性的影響および作用機序を解明し、ヒト神経系に及ぼす未知のリスクを明らかにすることを目的とした。
【方法】ヒト神経芽細胞腫（SH-SY5Y）に1–100 µMのCTDを曝露し、細胞数の変化を計測するとともに、細胞内シグナル状態の変化から機能的影響を評価し、各種nAChRsアンタゴニストの作用を検討した。加えて、マイクロアレイを用いてCTD曝露による遺伝子発現プロファイルの変化を解析した。
【結果・考察】CTD曝露群においては、培養24時間後以降に濃度依存的な細胞数の増加がみられ、その作用は広域アンタゴニストである mecamylamineおよびα3β4特異的アンタゴニストであるSR16584により消失した。また、CTD曝露直後においては一過性の細胞内カルシウム濃度の上昇、ならびにERKリン酸化レベルの上昇がみられた。Gene Ontology解析およびパスウェイ解析の結果、検出された発現低下遺伝子群は「カルシウムイオン流入」や「糸状仮足形成」等の細胞機能に関与しており、「軸索誘導」や「細胞骨格」に関するパスウェイが変動していることが示唆された。以上の結果から、ヒト神経芽細胞腫においてネオニコチノイド系農薬が機能的影響を及ぼすリスクが初めて明らかとなり、そのメカニズムとしてヒトnAChRs α3β4を介した細胞内カルシウムシグナルのかく乱が関連することが示唆された。
- 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, ［査読有り］
研究論文（学術雑誌） - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - 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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - Molecular and functional characterization of UDP-glucuronosyltransferase 1A in cynomolgus macaques
Uno Yasuhiro, Takahira Rika, Murayama Norie, Ishii Yu, Ikenaka Yoshinori, Ishizuka Mayumi, Yamazaki Hiroshi, Ikushiro Shinichi
BIOCHEMICAL PHARMACOLOGY, 155, 172, 181, 2018年09月, ［査読有り］, ［国際誌］
英語 - Occurrence and seasonal variation of equine estrogens, equilin and equilenin, in the river water of Japan: Implication with endocrine-disrupting potentials to Japanese medaka (Oryzias latipes)
Ishibashi Hiroshi, Uchida Masaya, Yoshimoto Keisuke, Imamura Yuta, Yamamoto Ryoko, Ikenaka Yoshinori, Kawai Masahito, Ichikawa Nobuhiro, Takao Yuji, Tominaga Nobuaki, Ishibashi Yasuhiro, Arizono Koji
ENVIRONMENTAL POLLUTION, 239, 281, 288, 2018年08月, ［査読有り］, ［国際誌］
英語 - Fish consumption from urban impoundments: What are the health risks associated with DDTs and other organochlorine pesticides in fish to township residents of a major inland city
Pheiffer Wihan, Wolmarans Nico J, Gerber Ruan, Yohannes Yared B, Ikenaka Yoshinori, Ishizuka Mayumi, Smit Nico J, Wepener Victor, Pieters Rialet
SCIENCE OF THE TOTAL ENVIRONMENT, 628-629, 517, 527, 2018年07月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌） - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - 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］, ［国内誌］
英語, 研究論文（学術雑誌） - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - 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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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. - Evaluation of mitochondrial redox status and energy metabolism of X-irradiated HeLa cells by LC/UV, LC/MS/MS and ESR
Kumiko Yamamoto, Yoshinori Ikenaka, Takahiro Ichise, Tomoki Bo, Mayumi Ishizuka, Hironobu Yasui, Wakako Hiraoka, Tohru Yamamori, Osamu Inanami
FREE RADICAL RESEARCH, 52, 6, 648, 660, 2018年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌） - The evolution of UDP-glycosyl/glucuronosyltransferase 1E (UGT1E) genes in bird lineages is linked to feeding habits but UGT2 genes is not.
Kawai YK, Ikenaka Y, Ishizuka M, Kubota A
PloS one, 13, 10, e0205266, 2018年, ［査読有り］, ［国際誌］
英語 - 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, 環境ホルモン学会(日本内分泌撹乱化学物質学会), 2017年12月, ［査読有り］
日本語 - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - 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, 24, 30, 23763, 23770, 2017年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌） - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - 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, 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, Sainnoxoi Tsend-ayush, 田辺 信介, 石塚 真由美
The Journal of Toxicological Sciences, 42, Suppl., S236, S236, (一社)日本毒性学会, 2017年06月, ［査読有り］
日本語 - 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］, ［国内誌］
英語, 研究論文（学術雑誌） - 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］, ［国内誌］
英語, 研究論文（学術雑誌） - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - 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］
英語, 研究論文（学術雑誌） - 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
SCIENCE OF THE TOTAL ENVIRONMENT, 574, 1389, 1395, 2017年01月, ［査読有り］
英語, 研究論文（学術雑誌） - Characterization of Species Differences in Xenobiotic Metabolism in Non-experimental Animals.
Hazuki Mizukawa, Yoshinori Ikenaka, Mayu Kakehi, Shouta Nakayama, Mayumi Ishizuka
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 137, 3, 257, 263, 2017年, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌） - 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
SCIENCE OF THE TOTAL ENVIRONMENT, 574, 1389, 1395, 2017年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌） - The African hedgehog (Atelerix albiventris): Low phase I and phase II metabolism activities.
Saengtienchai A, Ikenaka Y, Bortey-Sam N, Jermnark U, Mizukawa H, Kawai YK, Nakayama SM, Ishizuka M
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 190, 38, 47, 2016年12月, ［査読有り］, ［国際誌］
英語 - Excretion of polycyclic aromatic hydrocarbon metabolites (OH-PAHs) in cattle urine in Ghana.
Bortey-Sam N, Ikenaka Y, Akoto O, Nakayama SM, Marfo J, Saengtienchai A, Mizukawa H, Ishizuka M
Environmental pollution (Barking, Essex : 1987), 218, 331, 337, 2016年11月, ［査読有り］, ［国際誌］
英語 - English
Bortey Sam Nesta, M M Nakayama Shouta, Ikenaka Yoshinori, Akoto Osei, Baidoo Elvis, Mizukawa Hazuki, Ishizuka Mayumi
Journal of Environmental Chemistry and Ecotoxicology, 8, 7, 58, 68, Academic Journals, 2016年07月31日
研究論文（学術雑誌） - Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats.
Nishiyama Y, Nakayama SM, Watanabe KP, Kawai YK, Ohno M, Ikenaka Y, Ishizuka M
The Journal of veterinary medical science / the Japanese Society of Veterinary Science, 78, 4, 675, 80, 2016年05月03日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌） - Bioaccumulation and human health risk assessment of DDT and other organochlorine pesticides in an apex aquatic predator from a premier conservation area.
Gerber R, Smit NJ, Van Vuren JH, Nakayama SM, Yohannes YB, Ikenaka Y, Ishizuka M, Wepener V
The Science of the total environment, 550, 522, 533, 2016年04月15日, ［査読有り］, ［国際誌］
英語 - 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.
Mahmoud AF, Ikenaka Y, Yohannes YB, Darwish WS, Eldaly EA, Morshdy AE, Nakayama SM, Mizukawa H, Ishizuka M
Chemosphere, 144, 1365, 71, 2016年02月, ［査読有り］, ［国際誌］
英語 - 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 / the Japanese Society of Veterinary Science, 78, 2, 351, 4, 2016年02月, ［査読有り］, ［国内誌］
英語 - Organohalogen Compounds in Pet Dog and Cat: Do Pets Biotransform Natural Brominated Products in Food to Harmful Hydroxlated Substances?
Mizukawa H, Nomiyama K, Nakatsu S, Iwata H, Yoo J, Kubota A, Yamamoto M, Ishizuka M, Ikenaka Y, Nakayama SM, Kunisue T, Tanabe S
Environmental science & technology, 50, 1, 444, 52, 2016年01月05日, ［査読有り］, ［国際誌］
英語 - 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 (Barking, Essex : 1987), 208, Pt B, 395, 403, 2016年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌） - 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, T275-81, 81, 2016年01月, ［査読有り］, ［国際誌］
英語 - Application of a Sediment Quality Index for the assessment and monitoring of metals and organochlorines in a premier conservation area.
Gerber R, Smit NJ, van Vuren JH, Nakayama SM, Yohannes YB, Ikenaka Y, Ishizuka M, Wepener V
Environmental science and pollution research international, 22, 24, 19971, 89, 2015年12月, ［査読有り］, ［国際誌］
英語 - Accumulation properties of inorganic mercury and organic mercury in the red-crowned crane Grus japonensis in east Hokkaido, Japan.
Teraoka H, Okamoto E, Kudo M, Nakayama SM, Ikenaka Y, Ishizuka M, Endo T, Kitazawa T, Hiraga T
Ecotoxicology and environmental safety, 122, 557, 64, 2015年12月, ［査読有り］, ［国際誌］
英語 - Mutagenicity of modelled-heat-treated meat extracts: Mutagenicity assay, analysis and mechanism of mutagenesis.
Darwish WS, Ikenaka Y, Nakayama S, Mizukawa H, Ishizuka M
The Japanese journal of veterinary research, 63, 4, 173, 82, 2015年11月, ［査読有り］, ［国内誌］
英語 - Characterization and tissue distribution of conjugated metabolites of pyrene in the rat.
Saengtienchai A, Ikenaka Y, Darwish WS, Nakayama SM, Mizukawa H, Ishizuka M
The Journal of veterinary medical science / the Japanese Society of Veterinary Science, 77, 10, 1261, 7, 2015年10月, ［査読有り］, ［国内誌］
英語 - Uridine Diphosphate-Glucuronosyltransferase (UGT) Xenobiotic Metabolizing Activity and Genetic Evolution in Pinniped Species.
Kakehi M, Ikenaka Y, Nakayama SM, Kawai YK, Watanabe KP, Mizukawa H, Nomiyama K, Tanabe S, Ishizuka M
Toxicological sciences : an official journal of the Society of Toxicology, 147, 2, 360, 9, 2015年10月, ［査読有り］, ［国際誌］
英語 - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - 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 (Barking, Essex : 1987), 205, 8, 15, 2015年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌） - Ecological Risk of Heavy Metals and a Metalloid in Agricultural Soils in Tarkwa, Ghana.
Bortey-Sam N, Nakayama SM, Akoto O, Ikenaka Y, Baidoo E, Mizukawa H, Ishizuka M
International journal of environmental research and public health, 12, 9, 11448, 65, 2015年09月11日, ［査読有り］, ［国際誌］
英語 - 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］
英語, 研究論文（学術雑誌） - 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］
英語, 研究論文（学術雑誌） - Accumulation of Heavy Metals and Metalloid in Foodstuffs from Agricultural Soils around Tarkwa Area in Ghana, and Associated Human Health Risks.
Bortey-Sam N, Nakayama SM, Akoto O, Ikenaka Y, Fobil JN, Baidoo E, Mizukawa H, Ishizuka M
International journal of environmental research and public health, 12, 8, 8811, 27, 2015年07月28日, ［査読有り］, ［国際誌］
英語 - 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, ［査読有り］
英語, 研究論文（学術雑誌） - Health risk assessment of heavy metals and metalloid in drinking water from communities near gold mines in Tarkwa, Ghana.
Bortey-Sam N, Nakayama SM, Ikenaka Y, Akoto O, Baidoo E, Mizukawa H, Ishizuka M
Environmental monitoring and assessment, 187, 7, 397, 397, 2015年07月, ［査読有り］, ［国際誌］
英語 - Metabolic Activation of Heterocyclic Amines and Expression of Xenobiotic-Metabolizing Enzymes in the Gastrointestinal Tract of Rats.
Darwish WS, Nakayama SM, Itotani Y, Ohno M, Ikenaka Y, Ishizuka M
Journal of food science, 80, 7, T1627-32, 32, 2015年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌） - Levels, potential sources and human health risk of polycyclic aromatic hydrocarbons (PAHs) in particulate matter (PM10) in Kumasi, Ghana.
Bortey-Sam N, Ikenaka Y, Akoto O, Nakayama SM, Yohannes YB, Baidoo E, Mizukawa H, Ishizuka M
Environmental science and pollution research international, 22, 13, 9658, 67, 2015年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌） - Are red gourami (Colisa labiosa) low xenobiotic metabolizers? Elucidation of in vivo pharmacokinetics of pyrene as a model substrate.
Ikenaka Y, Nakayama SM, Oguri M, Saengtienchai A, Mizukawa H, Kobayashi J, Darwish WS, Ishizuka M
Environmental toxicology and pharmacology, 39, 3, 1148, 53, 2015年05月, ［査読有り］, ［国際誌］
英語 - Relationship between Urinary N-Desmethyl-Acetamiprid and Typical Symptoms including Neurological Findings: A Prevalence Case-Control Study.
Marfo JT, Fujioka K, Ikenaka Y, Nakayama SM, Mizukawa H, Aoyama Y, Ishizuka M, Taira K
PloS one, 10, 11, e0142172, 2015年, ［査読有り］, ［国際誌］
英語 - 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).
Bortey-Sam N, Nakayama SM, Ikenaka Y, Akoto O, Baidoo E, Yohannes YB, Mizukawa H, Ishizuka M
Ecotoxicology and environmental safety, 111, 160, 7, 2015年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌） - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - Occurrence, distribution, sources and toxic potential of polycyclic aromatic hydrocarbons (PAHs) in surface soils from the Kumasi Metropolis, Ghana.
Bortey-Sam N, Ikenaka Y, Nakayama SM, Akoto O, Yohannes YB, Baidoo E, Mizukawa H, Ishizuka M
The Science of the total environment, 496, 471, 478, 2014年10月15日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌） - 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］, ［国際誌］
英語 - Identification of interspecific differences in phase II reactions: determination of metabolites in the urine of 16 mammalian species exposed to environmental pyrene.
Saengtienchai A, Ikenaka Y, Nakayama SM, Mizukawa H, Kakehi M, Bortey-Sam N, Darwish WS, Tsubota T, Terasaki M, Poapolathep A, Ishizuka M
Environmental toxicology and chemistry / SETAC, 33, 9, 2062, 9, 2014年09月, ［査読有り］, ［国際誌］
英語 - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - 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, 2014年08月17日, ［査読有り］, ［国際誌］
英語 - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - 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.
Mizukawa H, Ikenaka Y, Nakayama SM, Sakamoto KQ, Fujita S, Ishizuka M
The Japanese journal of veterinary research, 62, 3, 107, 15, 2014年08月, ［査読有り］, ［国内誌］
英語 - Contamination status and accumulation characteristics of metals and a metalloid in birds on Teuri Island, Hokkaido, Japan.
Ishii C, Ikenaka Y, Nakayama SM, Suzuki Y, Watanuki Y, Watanabe Y, Yohannes YB, Mizukawa H, Ishizuka M
The Japanese journal of veterinary research, 62, 3, 143, 9, 2014年08月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌） - An overview on mycotoxin contamination of foods in Africa.
Darwish WS, Ikenaka Y, Nakayama SM, Ishizuka M
The Journal of veterinary medical science / the Japanese Society of Veterinary Science, 76, 6, 789, 97, 2014年06月, ［査読有り］, ［国内誌］
英語 - Radiosensitization of tumor cells through endoplasmic reticulum stress induced by PEGylated nanogel containing gold nanoparticles
Hironobu Yasui, Ryo Takeuchi, Masaki Nagane, Shunsuke Meike, Yoshinari Nakamura, Tohru Yamamori, Yoshinori Ikenaka, Yasuhiro Kon, Hiroki Murotani, Motoi Oishi, Yukio Nagasaki, Osamu Inanami
CANCER LETTERS, 347, 1, 151, 158, 2014年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌） - The effect of copper on the mRNA expression profile of xenobiotic-metabolizing enzymes in cultured rat H4-II-E cells.
Darwish WS, Ikenaka Y, Nakayama S, Ishizuka M
Biological trace element research, 158, 2, 243, 8, 2014年05月, ［査読有り］, ［国際誌］
英語 - Toxicokinetics and tissue depletion of Fusarenon-X and its metabolite nivalenol in piglets.
Saengtienchai T, Poapolathep S, Isariyodom S, Ikenaka Y, Ishizuka M, Poapolathep A
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 66, 307, 12, 2014年04月, ［査読有り］, ［国際誌］
英語 - Molecular Characterization and mRNA Expression of Cytochrome P450 1A1 and Cytochrome P450 3A in Liver of Kafue Lechwe (Kobus leche kafuensis) as Potential Biomarkers of Pollution of the Kafue River Basin, Zambia
M'kandawire, Ethel, Syakalima, Michelo, Muzandu, Kaampwe, Pandey, Girja, Simuunza, Martin, Nakayama, Shouta M. M, Kawai, Yusuke K, Ikenaka, Yoshinori, Ishizuka, Mayumi
Engineering, 6, 2, 51, 58, 2014年02月, ［査読有り］
英語, 研究論文（学術雑誌） - 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
論文集(書籍)内論文 - 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］
英語 - Dioxin sensitivity-related two critical amino acids of arylhydrocarbon receptor may not correlate with the taxonomy or phylogeny in avian species.
Fujisawa N, Kawai YK, Nakayama SM, Ikenaka Y, Yamamoto H, Ishizuka M
The Journal of veterinary medical science / the Japanese Society of Veterinary Science, 75, 12, 1577, 83, 2013年12月30日, ［査読有り］, ［国内誌］
英語 - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - Repeated Treatment with Furazolidone Induces Multiple Cytochrome P450-Related Activities in Chicken Liver, but Not in Rat Liver
Sasaki Nobuo, Matumoto Tomoyuki, Ikenaka Yoshinori, Nakayama Shouta M. M, Ishizuka Mayumi, Kazusaka Akio, Fujita Shoichi
JOURNAL OF VETERINARY MEDICAL SCIENCE, 75, 11, 1497, 502, 2013年11月, ［査読有り］, ［国内誌］
英語 - De novo sequence analysis of cytochrome P450 1-3 genes expressed in ostrich liver with highest expression of CYP2G19.
Kawai YK, Watanabe KP, Ishii A, Ohnuma A, Sawa H, Ikenaka Y, Ishizuka M
Comparative biochemistry and physiology. Part D, Genomics & proteomics, 8, 3, 201, 8, 2013年09月, ［査読有り］, ［国際誌］
英語 - Characterization of phase-II conjugation reaction of polycyclic aromatic hydrocarbons in fish species: unique pyrene metabolism and species specificity observed in fish species.
Ikenaka Y, Oguri M, Saengtienchai A, Nakayama SM, Ijiri S, Ishizuka M
Environmental toxicology and pharmacology, 36, 2, 567, 578, 2013年09月, ［査読有り］, ［国際誌］
英語 - Accumulation and biological effects of metals in wild rats in mining areas of Zambia.
Nakayama SM, Ikenaka Y, Hamada K, Muzandu K, Choongo K, Yabe J, Umemura T, Ishizuka M
Environmental monitoring and assessment, 185, 6, 4907, 18, 2013年06月, ［査読有り］, ［国際誌］
英語 - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - Antibiotic residues in food: the African scenario.
Darwish WS, Eldaly EA, El-Abbasy MT, Ikenaka Y, Nakayama S, Ishizuka M
The Japanese journal of veterinary research, 61 Suppl, S13-22, 22, 2013年02月, ［査読有り］, ［国内誌］
英語 - Biological responses of xenobiotic metabolizing enzymes to lead exposure in cultured H4IIE rat cells.
Darwish WS, Ikenaka Y, Ishizuka M
The Japanese journal of veterinary research, 61 Suppl, S48-53, 53, 2013年02月, ［査読有り］, ［国内誌］
英語 - Determination of organochlorine pesticides (OCPs) in the edible offal of Egyptian buffalo.
Mahmoud AF, Darwish WS, Morshdy AE, Eldaly EA, Ikenaka Y, Ishizuka M
The Japanese journal of veterinary research, 61 Suppl, S58-63, 63, 2013年02月, ［査読有り］, ［国内誌］
英語 - Distribution of metals in organs of Clarias gariepinus, Heterobranchus bidorsalis, and Chrysichthys nigrodigitatus from the Offin River at Dunkwa-on-Offin, Ghana.
Marfo JT, Akoto O, Nakayama SM, Baidoo E, Ikenaka Y, Ishizuka M
The Japanese journal of veterinary research, 61 Suppl, S69-71, 71, 2013年02月, ［査読有り］, ［国内誌］
英語 - Determination of benzo[a]pyrene levels in ambient air and the source of polycyclic aromatic hydrocarbons using a diagnostic ratio method in Ghana.
Bortey-Sam N, Akoto O, Ikenaka Y, Nakayama SM, Ishizuka M
The Japanese journal of veterinary research, 61 Suppl, S72-4, 4, 2013年02月, ［査読有り］, ［国内誌］
英語 - Heavy metal pollution in Japanese seabirds.
Ishii C, Ikenaka Y, Nakayama SM, Suzuki Y, Watanuki Y, Watanabe Y, Fukuwaka MA, Yohannes YB, Kawai YK, Ishizuka M
The Japanese journal of veterinary research, 61 Suppl, S75-6, 6, 2013年02月, ［査読有り］, ［国内誌］
英語 - Metabolism of pyrene, a polycyclic aromatic hydrocarbon in freshwater turtles.
Oroszlany B, Ikenaka Y, Saengtiengchan A, Oguri M, Nakayama SM, Ishizuka M
The Japanese journal of veterinary research, 61 Suppl, S77-8, 8, 2013年02月, ［査読有り］, ［国内誌］
英語 - Metal contaminated soil from mining area caused metal accumulation and biological responses in rats.
Nakayama SM, Ikenaka Y, Muzandu K, Choongo K, Yabe J, Umemura T, Ishizuka M
The Japanese journal of veterinary research, 61 Suppl, S79-81, 81, 2013年02月, ［査読有り］, ［国内誌］
英語 - In vitro diazepam metabolism in horses.
Hayami A, Darwish WS, Ikenaka Y, Nakayama SM, Ishizuka M
The Japanese journal of veterinary research, 61 Suppl, S82-4, 4, 2013年02月, ［査読有り］, ［国内誌］
英語 - Effects of polycyclic aromatic hydrocarbons (PAHs) on an aquatic ecosystem: acute toxicity and community-level toxic impact tests of benzo[a]pyrene using lake zooplankton community.
Ikenaka Y, Sakamoto M, Nagata T, Takahashi H, Miyabara Y, Hanazato T, Ishizuka M, Isobe T, Kim JW, Chang KH
The Journal of toxicological sciences, 38, 1, 131, 6, 2013年02月, ［査読有り］, ［国内誌］
英語 - Effects of polycyclic aromatic hydrocarbons (PAHs) on an aquatic ecosystem: acute toxicity and community-level toxic impact tests of benzo[a]pyrene using lake zooplankton community
Yoshinori Ikenaka, Masaki Sakamoto, Takamaru Nagata, Hirokazu Takahashi, Yuichi Miyabara, Takayuki Hanazato, Mayumi Ishizuka, Tomohiko Isobe, Jun-Woo Kim, Kwang-Hyeon Chang
JOURNAL OF TOXICOLOGICAL SCIENCES, 38, 1, 131, 136, 2013年02月, ［査読有り］
英語, 研究論文（学術雑誌） - A Novel Mutation in VKORC1 and Its Effect on Enzymatic Activity in Japanese Warfarin-Resistant Rats
Tanaka Kazuyuki D, Kawai Yusuke K, Ikenaka Yoshinori, Harunari Tsunehito, Tanikawa Tsutomu, Fujita Shoichi, Ishizuka Mayumi
JOURNAL OF VETERINARY MEDICAL SCIENCE, 75, 2, 135, 9, 2013年02月, ［査読有り］, ［国内誌］
英語 - 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.
Nakayama SM, Ikenaka Y, Muzandu K, Choongo K, Yabe J, Muroya T, Ijiri S, Minagawa M, Umemura T, Ishizuka M
Archives of environmental contamination and toxicology, 64, 1, 119, 29, 2013年01月, ［査読有り］, ［国際誌］
英語 - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - Avian cytochrome P450 (CYP) 1-3 family genes: isoforms, evolutionary relationships, and mRNA expression in chicken liver.
Watanabe KP, Kawai YK, Ikenaka Y, Kawata M, Ikushiro S, Sakaki T, Ishizuka M
PloS one, 8, 9, e75689, 2013年, ［査読有り］, ［国際誌］
英語 - Cytochrome P450 3A mRNA expression along goat and rat gastrointestinal tracts.
Mureithi D, Darwish WS, Ikenaka Y, Kanja L, Ishizuka M
The Japanese journal of veterinary research, 60, 4, 205, 10, 2012年11月, ［査読有り］, ［国内誌］
英語 - 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］, ［国内誌］
英語, 研究論文（学術雑誌） - 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.
Ikenaka Y, Nakayama SM, Muroya T, Yabe J, Konnai S, Darwish WS, Muzandu K, Choongo K, Mainda G, Teraoka H, Umemura T, Ishizuka M
Environmental toxicology and chemistry / SETAC, 31, 10, 2300, 5, 2012年10月, ［査読有り］, ［国際誌］
英語 - 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.
M'kandawire E, Syakalima M, Muzandu K, Pandey G, Simuunza M, Nakayama SM, Kawai YK, Ikenaka Y, Ishizuka M
Gene, 506, 2, 310, 6, 2012年09月15日, ［査読有り］, ［国際誌］
英語 - Transcriptional profiling of inflammatory cytokine genes in African buffaloes (Syncerus caffer) infected with Theileria parva.
Tomohiro Okagawa, Satoru Konnai, Hirohisa Mekata, Naftaly Githaka, Saori Suzuki, Edward Kariuki, Francis Gakuya, Esther Kanduma, Tatsuya Shirai, Ryoyo Ikebuchi, Yoshinori Ikenaka, Mayumi Ishizuka, Shiro Murata, Kazuhiko Ohashi
Veterinary immunology and immunopathology, 148, 3-4, 373, 9, 2012年08月15日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌） - 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 SM, Ikenaka Y, Muzandu K, Choongo K, M'kandawire E, Yasuda J, Ishizuka M
Ecotoxicology and environmental safety, 80, 333, 8, 2012年06月, ［査読有り］, ［国際誌］
英語 - All-trans retinoic acid inhibits the recruitment of ARNT to DNA, resulting in the decrease of CYP1A1 mRNA expression in HepG2 cells.
Ohno M, Ikenaka Y, Ishizuka M
Biochemical and biophysical research communications, 417, 1, 484, 9, 2012年01月06日, ［査読有り］, ［国際誌］
英語 - Cross-talks between heavy metals and xenobiotics metabolizing enzymes
DARWISH Wageh S., IKENAKA Yoshinori, ISHIZUKA Mayumi
日本毒性学会学術年会, 39, O, 6, 日本毒性学会, 2012年
日本語, [Introduction] The growing exposure of the human and animals to heavy metal pollution generates modulation in xenobiotics-metabolizing enzymes (XMEs) response. In this study, the modulation of Ahr ligand-dependent toxicities by heavy metals and the molecular basis of this modulation were investigated.[Materials and Methods] Samples were collected from different edible offal of cattle slaughtered at Zagazig abattoir, Egypt. Different heavy metals were measured using atomic absorption spectrophotometer. Human and rat liver hepatoma cell lines (HEPG2 and H4IIE) were treated with Lead and Copper under different concentrations ranged between permissible and toxic doses. The effects of these treatments on various XMEs and regulatory elements were screened using the methods of qPCR and Western Blotting.[Results and Discussion] Liver, kidney and tongue showed the highest contents of the various heavy metal residues compared to other tissues. Lead, copper, cadmium, zinc and nickel exceeded the maximum permissible limits of Egyptian Standards and WHO. Interestingly, both copper and lead could induce CYP1A1 mRNA expression under low doses in the treated cell cultures. This expression level was markedly decreased under high concentrations. Effects of copper and lead on CYP1A1 expression was parallel to their effects on Ahr suggesting that those effects were in response to Ahr. All tested phase II enzymes were severely down regulated by exposure to lead in a concentration dependent manner. In conclusion, there were clear cross-talks between copper, lead and pase I, II enzymes and regulatory elements in the cultured cells. - The identification of the important CYP isoforms in avian xenobiotic metabolism and its species difference among bird species
WATANABE Kensuke P, KAWATA Minami, KAWAI Yusuke, IKENAKA Yoshinori, ISHIZUKA Mayumi
日本毒性学会学術年会, 39, AP, 223, 日本毒性学会, 2012年
日本語, [Background and aim]In wild bird species, the metabolic activity of warfarin by cytochrome P450 (CYP) was reported to be much lower compared to chicken. However, even the important CYP isoforms in avian xenobiotic metabolism have not been clarified due to the lack of information about the expression level and the function of each isoforms. Thus, the reported species difference of metabolic ability cannot be attributed to any isoform. In this study, we aimed to identify the isoform dominant in avian xenobiotic metabolism and to characterize the species difference of the isoform.[Method and result]We compared the mRNA copy number among CYP isoforms in chicken liver. CYP1A5, 2C23 and 2C45 were highly expressed in liver, while CYP3A37, which has been well studied in poultry species, showed lower expression level. Therefore, we focused on CYP2C23 of avian species. Partial sequences of CYP2C23 from 8 avian species were cloned and the anti-peptide antibody was synthesized against the conserved amino acid sequence among them. In immunoblot with the antibody and the microsomes of the avian species, we could detect CYP2C23s from all the avian species.[Discussion]With mRNA expression, CYP2C subfamily was assumed to be important isoforms in chicken xenobiotics metabolism. The expression levels of CYP2C23 proteins showed not as much difference among bird species as the metabolic activity. With all results above, the species difference of metabolic ability among bird species cannot be attributed to the protein expression levels, but the functional difference. - The study of polycyclic aromatic hydrocarbons (PAHs) and its metabolite as a biomarker for PAH exposures in wildlife animals
SAENGTIENCAHI Aksorn, IKENAKA Yoshinori, LEE Kyunglee, TSUBOTA Toshio, ISHIZUKA Mayumi
日本毒性学会学術年会, 39, P, 125, 日本毒性学会, 2012年
日本語, [Introduction] Polycyclic aromatic hydrocarbons (PAHs) distribute ubiquitously as complex mixtures in the environment. Pyrene is one of PAHs that is widely used as model of PAH contamination in environment. Pyrene is metabolized by cytochrome P450s in phase I reaction then conjugated in phase II metabolism, and excreted into urine and feces. Although their metabolites are available for use in human as indicator for PAH exposure, there are still less information in wildlife. In present study, we focus on the elucidation of pyrene metabolites in wild animals. [Materials and Methods] Urine of 10 male sika deer (Cervus nippon), 1 to 5 year olds were collected from Hokkaido, Japan. All samples were extracted by Oasis WAX cartridge and they were analyzed by High performance liquid chromatography with fluorescence detector. [Results and Discussions] We could detect pyrene-1-glucuronide largely in urine. Moreover, pyrene-1-sulfate, and 1-hydroxypyrene also detected. When we compared this results with other ruminant as cattle, pyrene-1-glucuronide was main metabolites same as sika deer. Pyrene conjugate compounds were easily detected in urine. Due to observe the amount of polluted chemical as PAHs in environment, we could suggest that not only elucidate PAH concentration, but also its metabolite as 1-hydroxypyrene, pyrene 1-glucuronide, and sulfate conjugates were important to establish the appropriate biomarker for the assessment for PAH exposures in various wildlife animal species in environment. - Sudan III dye strongly induces CYP1A1 mRNA expression in HepG2 cells.
Ohno M, Ikenaka Y, Ishizuka M
Journal of biochemical and molecular toxicology, 26, 1, 16, 22, 2012年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌） - Phase-II conjugation ability for PAH metabolism in amphibians: characteristics and inter-species differences.
Ueda H, Ikenaka Y, Nakayama SM, Tanaka-Ueno T, Ishizuka M
Aquatic toxicology (Amsterdam, Netherlands), 105, 3-4, 337, 43, 2011年10月, ［査読有り］, ［国際誌］
英語 - 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］, ［国際誌］
英語, 研究論文（学術雑誌） - Astaxanthin can alter CYP1A-dependent activities via two different mechanisms: induction of protein expression and inhibition of NADPH P450 reductase dependent electron transfer.
Ohno M, Darwish WS, Ikenaka Y, Miki W, Ishizuka M
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 49, 6, 1285, 91, 2011年06月, ［査読有り］, ［国際誌］
英語 - Metal and metalloid contamination in roadside soil and wild rats around a Pb-Zn mine in Kabwe, Zambia.
Nakayama SM, Ikenaka Y, Hamada K, Muzandu K, Choongo K, Teraoka H, Mizuno N, Ishizuka M
Environmental pollution (Barking, Essex : 1987), 159, 1, 175, 181, 2011年01月, ［査読有り］, ［国際誌］
英語 - Carotenoids as regulators for inter-species difference in cytochrome P450 1A expression and activity in ungulates and rats.
Darwish WS, Ikenaka Y, Ohno M, Eldaly EA, Ishizuka M
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 48, 11, 3201, 8, 2010年11月, ［査読有り］, ［国際誌］
英語 - Identification and Phylogenetic Analysis of Novel Cytochrome P450 1A Genes from Ungulate Species
Wageh Sobhy Darwish, Yusuke Kawai, Yoshinori Ikenaka, Hideaki Yamamoto, Tarou Muroya, Mayumi Ishizuka
JOURNAL OF VETERINARY MEDICAL SCIENCE, 72, 9, 1237, 1241, 2010年09月, ［査読有り］
英語, 研究論文（学術雑誌） - Identification and Phylogenetic Analysis of Novel Cytochrome P450 1A Genes from Ungulate Species
Darwish Wageh Sobhy, Kawai Yusuke, Ikenaka Yoshinori, Yamamoto Hideaki, Muroya Tarou, Ishizuka Mayumi
JOURNAL OF VETERINARY MEDICAL SCIENCE, 72, 9, 1237, 41, 2010年09月, ［査読有り］, ［国内誌］
英語 - Heavy metal accumulation in lake sediments, fish (Oreochromis niloticus and Serranochromis thumbergi), and crayfish (Cherax quadricarinatus) in Lake Itezhi-tezhi and Lake Kariba, Zambia.
Nakayama SM, Ikenaka Y, Muzandu K, Choongo K, Oroszlany B, Teraoka H, Mizuno N, Ishizuka M
Archives of environmental contamination and toxicology, 59, 2, 291, 300, 2010年08月, ［査読有り］, ［国際誌］
英語 - Metabolic activation of heterocyclic amines and expression of CYP1A1 in the tongue.
Takiguchi M, Darwish WS, Ikenaka Y, Ohno M, Ishizuka M
Toxicological sciences : an official journal of the Society of Toxicology, 116, 1, 79, 91, 2010年07月, ［査読有り］, ［国際誌］
英語 - Comparison of warfarin sensitivity between rat and bird species.
Watanabe KP, Saengtienchai A, Tanaka KD, Ikenaka Y, Ishizuka M
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 152, 1, 114, 9, 2010年06月, ［査読有り］, ［国際誌］
英語 - The CYP1D subfamily of genes in mammals and other vertebrates.
Kawai YK, Ikenaka Y, Fujita S, Ishizuka M
Mammalian genome : official journal of the International Mammalian Genome Society, 21, 5-6, 320, 9, 2010年06月, ［査読有り］, ［国際誌］
英語 - Cytochrome P450 1A-dependent activities in deer, cattle and horses.
Darwish WS, Ikenaka Y, Eldaly EA, Ohno M, Sakamoto KQ, Fujita S, Ishizuka M
The Journal of veterinary medical science / the Japanese Society of Veterinary Science, 72, 5, 561, 6, 5, 2010年05月, ［査読有り］, ［国内誌］
英語, The objective of this study was to investigate and characterize the metabolic activities of CYP1A in deer, cattle and horses in comparison to those of rats using ethoxyresorufin O-deethylation (EROD) and methoxyresorufin O-demethylation (MROD) assays. We performed an inhibition study for these activities using anti-rat CYP1A1 antibody and identified that these activities were due to the CYP1A subfamily. Interspecies differences in the CYP1A-dependent activities were highly observed in this study. In particular, we found that the horse had the highest EROD and MROD activities among the examined animal species. In the kinetic analysis, the horses showed the highest Vmax and catalytic efficiency (Vmax/Km), followed by the cattle, deer and rats. - Cytochrome P450 1A-Dependent Activities in Deer, Cattle and Horses
Wageh Sobhy Darwish, Yoshinori Ikenaka, Elsaid Abozeid Eldaly, Marumi Ohno, Kentaro Q. Sakamoto, Shoichi Fujita, Mayumi Ishizuka
JOURNAL OF VETERINARY MEDICAL SCIENCE, 72, 5, 561, 566, 2010年05月, ［査読有り］
英語, 研究論文（学術雑誌） - Expression and sequence of CYP1A1 in the camel.
Darwish WS, Morshdy AE, Ikenaka Y, Ibrahim ZS, Fujita S, Ishizuka M
The Journal of veterinary medical science / the Japanese Society of Veterinary Science, 72, 2, 221, 4, 2, 2010年02月, ［査読有り］, ［国内誌］
英語, In this study, we determined a partial sequence of CYP1A1 in the camel and its phylogenetic position. The deduced amino acid sequence of camel CYP1A1 showed the highest identity 94% with those of sheep and cattle CYP1A1. In a phylogenetic analysis, the camel CYP1A1 isoform was located beside sheep and cattle CYP1A1. When we studied the distribution of camel CYP1A1 mRNA in different tissues, we found that this isoform was expressed in all tissues except the hump. Interestingly, the lungs of all the camels and tongues of two of the three animals showed high expressions of CYP1A1 mRNA, and this may indicate exposure to ligands of aryl hydrocarbon receptor such as environmental pollutants or flavonoids. - Expression and Sequence of CYP1A1 in the Camel
Wageh Sobhy Darwish, Alaa Eldin Morshdy, Yoshinori Ikenaka, Zein Shaban Ibrahim, Shoichi Fujita, Mayumi Ishizuka
JOURNAL OF VETERINARY MEDICAL SCIENCE, 72, 2, 221, 224, 2010年02月, ［査読有り］
英語, 研究論文（学術雑誌） - Protective effect of Pleurotus cornucopiae mushroom extract on carbon tetrachloride-induced hepatotoxicity.
El BK, Hashimoto Y, Muzandu K, Ikenaka Y, Ibrahim ZS, Kazusaka A, Fujita S, Ishizuka M
The Japanese journal of veterinary research, 57, 2, 109, 18, 2009年08月, ［査読有り］, ［国内誌］
英語 - Antibiotic furazolidone induces CYP1A but not CYP2E1 subfamily in rat liver.
Sasaki N, Sakai N, Ikenaka Y, Kamiya T, Heewon M, Sakamoto KQ, Ishizuka M, Fujita S
The Journal of veterinary medical science / the Japanese Society of Veterinary Science, 70, 3, 223, 6, 3, 2008年03月, ［査読有り］, ［国内誌］
英語, Furazolidone (FZ), one of the nitrofuran fungicides, is used as a veterinary medicine in the Middle and Far Eastern countries. In this study, FZ (125 mg/kg) was administered orally to Wistar rats for 3 days. Results of the Ames test using the S-9 fraction of rats treated with FZ showed a significant increase in the number of revertant colonies. Western blot analysis of hepatic CYP isozymes induced by FZ, revealed a remarkable induction of CYP1A1 apoprotein, but CYP1A2 and CYP2E1 apoproteins were not altered. In addition, the expression of CYP1A1 mRNA level in rats treated with FZ by RT-PCR was significantly enhanced by FZ treatment. We concluded that FZ is apparently mutagenic and induces transcription of the CYP1A1 isozyme, which metabolically activates numerous promutagens, in hepatocytes. - Glucose-sulfate conjugates as a new phase II metabolite formed by aquatic crustaceans.
Ikenaka Y, Ishizaka M, Eun H, Miyabara Y
Biochemical and biophysical research communications, 360, 2, 490, 5, 2007年08月24日, ［査読有り］, ［国際誌］
英語 - Metabolism of pyrene by aquatic crustacean, Daphnia magna.
Ikenaka Y, Eun H, Ishizaka M, Miyabara Y
Aquatic toxicology (Amsterdam, Netherlands), 80, 2, 158, 65, 2006年11月16日, ［査読有り］, ［国際誌］
英語 - Estimation of sources and inflow of dioxins and polycyclic aromatic hydrocarbons from the sediment core of Lake Suwa, Japan.
Ikenaka Y, Eun H, Watanabe E, Kumon F, Miyabara Y
Environmental pollution (Barking, Essex : 1987), 138, 3, 529, 37, 3, 2005年12月, ［査読有り］, ［国際誌］
英語, To elucidate the historical changes in polychlorinated dibenzo-p-dioxin (PCDD), polychlorinated dibenzofuran (PCDF), coplanar polychlorinated biphenyl (co-PCB), and polycyclic aromatic hydrocarbon (PAH) inflows in Lake Suwa, their concentrations in the sediment core were analyzed in 5 cm interval. The maximum concentrations (depth cm) of PCDDs/DFs, co-PCBs, and PAHs were 25.2 ng/g dry (30-35 cm), 19.0 ng/g dry (30-35 cm), and 738, 795 ng/g dry (50-55 cm, 30-35 cm), respectively. Age and sedimentation rate of the sediment were estimated from the vertical changes in apparent density. Deposition rate of dioxins and PAHs were calculated from the concentration and sedimentation rate of the sediment. The results indicate that large amounts of dioxins and PAHs flowed into the lake in flood stage compared to normal stage.
その他活動・業績
- 小笠原諸島父島の外来クマネズミにおける殺鼠剤ダイファシノンの薬物動態・薬力学(PK/PD)解析による感受性評価
田中康太郎, 清水敬太, 佐藤美侑, 片山雅史, 中山翔太, 近藤理美, 池中良徳, 一瀬貴大, 石塚真由美, 鎌田亮, 小山田佑輔, 港隆一, 橋本琢磨, 田中和之, 木村悟朗, 谷川力, 加藤恵介, 日下部太一, 武田一貴, 環境化学討論会要旨集(CD-ROM), 32nd, 2024年 - 高病原性鳥インフルエンザウイルス感染の治療を目指したヒト用抗インフルエンザ薬のユーラシアワシミミズクへの投与試験
島津 陽, 尾原 涼, 西村 享平, 三木 万梨子, 佐渡 晃浩, 境 秀文, 磯田 典和, 日尾野 隆大, 宍戸 貴雄, 齊藤 慶輔, 池中 良徳, 迫田 義博, 日本野生動物医学会誌, 28, Suppl., 164, 165, 2023年12月
日本野生動物医学会, 日本語 - AlphaFold2と分子シミュレーションを活用した天然記念物オガサワラオオコウモリの殺鼠剤感受性評価
武田一貴, 武田一貴, 川合佑典, 安尾信明, 関嶋政和, 真砂皓大, 池中良徳, 堀越和夫, 鈴木創, 石塚真由美, 中山翔太, 環境化学討論会要旨集(CD-ROM), 31st, 2023年 - 北海道スタディ,思春期小児調査からみえる,将来的なNon-communicable Diseasesリスク
山口健史, 山口健史, 曾怡, 池田敦子, 池田敦子, KETEMA Rahel Mesfin, KETEMA Rahel Mesfin, アイツバマイ ゆふ, アイツバマイ ゆふ, 宮下ちひろ, 池中良徳, 池中良徳, 今雅史, 中村明枝, 岸玲子, 北海道公衆衛生学雑誌, 37, 1, 2023年 - 乳牛の分娩前の体温低下,ホルモン動態および分娩経過の関連について
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小笠原浩平, 山田尚輝, 千葉茜, 内田義崇, 境秀文, 竹中康進, 風間健太郎, 風間麻未, 山岸潤也, 池中良徳, 中山翔太, 石塚真由美, 日本野生動物医学会大会・講演要旨集, 29th, 2023年 - 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
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原悠佳子, 世ノ一さくら, 石田祐也, 伊藤槙子, 布引沙利香, 吉本彩乃, 万谷洋平, 横山俊文, 平野哲史, 池中良徳, 星信彦, 日本獣医学会学術集会講演要旨集, 166th, 2023年 - 胎児期フタル酸エステル類曝露による思春期発来への影響 北海道スタディ
山口 健史, 池田 敦子, アイツバマイ ゆふ, 宮下 ちひろ, 池中 良徳, 中村 明枝, 今 雅史, 藤谷 倫子, 原田 浩二, 岸 玲子, DOHaD研究, 10, 2, 46, 46, 2022年10月
(一社)日本DOHaD学会, 日本語 - 神経毒性のAOPにおける共通Key Eventを指標とした農薬類の複合影響評価
平野哲史, 池中良徳, 星信彦, 田渕圭章, 環境化学討論会要旨集(CD-ROM), 30th, 2022年 - 環境ストレス負荷下におけるネオニコチノイド系農薬曝露が腸内細菌叢に及ぼす影響
世ノ一さくら, 石田祐也, 原悠佳子, 木村真子, 正田明日香, 村田碧, 万谷洋平, 横山俊史, 平野哲史, 池中良徳, 池中良徳, 星信彦, 日本獣医学会学術集会講演要旨集, 165th (CD-ROM), 2022年 - 胎子授乳期ネオニコチノイド系農薬曝露が海馬記憶と運動学習に及ぼす次世代影響
原悠佳子, 世ノ一さくら, 石田祐也, 正田明日香, 村田碧, 木村真子, 万谷洋平, 横山俊史, 平野哲史, 池中良徳, 池中良徳, 星信彦, 日本獣医学会学術集会講演要旨集, 165th (CD-ROM), 2022年 - 人と動物の健康を守るワンヘルスの取組み-北海道大学One Healthリサーチセンターの活動紹介-
堀内基広, 池中良徳, 山崎淳平, 佐藤豊孝, 鈴木章夫, 直亨則, 松野啓太, 澤洋文, 日本獣医師会獣医学術学会年次大会講演要旨集, 2022, 2022年 - 神経毒性に関するAdverse Outcome Pathway（AOP）に基づいた農薬類の複合影響評価
平野 哲史, 池中 良徳, 星 信彦, 田渕 圭章, 日本毒性学会学術年会, 49.1, P-4E, 2022年
【背景・目的】化学物質のリスク評価における課題の一つとして、個々の化学物質を対象とする従来の毒性評価システムによっては複数の化学物質による複合影響のリスクを評価できない点が挙げられる。近年提唱されたAdverse Outcome Pathway（AOP）の概念に基づくと、複合影響に対する効率的な毒性評価を行うためには毒性発現における共通のKey Eventを活用することが重要となる。我々は前回大会にて、ピレスロイド系農薬デルタメトリン曝露時において、マイトファジーの活性化およびプロテアソーム活性低下を介したタンパク質分解系の不均衡状態が関与する新たな神経毒性メカニズムを報告した。そこで本研究では、これらのエンドポイントを神経毒性のKey Eventとすることで農薬類の複合影響評価への応用を検証することを目的とした。
【方法】マウス神経芽細胞腫Neuro-2a細胞に農薬類10種を曝露し、ミトコンドリア膜電位やオートファジーおよびプロテアソーム活性を指標としてミトコンドリアやタンパク質分解系への機能的影響を評価した。またWST-8アッセイにより細胞生存性を評価し、CompuSynソフトウェアにより複合影響の用量反応性を解析した。
【結果・考察】ピレスロイド系農薬ペルメトリンおよびデルタメトリンとフェニルピラゾール系農薬フィプロニルの曝露により、ミトコンドリアの機能低下、オートファジーの分解基質マーカーであるp62の蓄積等の共通したKey Eventの変動がみられた。さらにこれらの複合曝露により、単独曝露時と比べてより低濃度で細胞生存性が低下し、Combination Index < 1を示す相乗効果が認められた。本研究により、神経毒性に関するAOPの共通Key Eventを指標とすることで異種の農薬類の複合曝露が引き起こす相乗的な神経毒性を検出できることが初めて示された。, 日本毒性学会, 日本語 - 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
環境ホルモン学会(日本内分泌撹乱化学物質学会), 日本語 - 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
(公社)日本獣医学会, 英語 - 超音波で生体の壁を超える 超音波と気泡を併用する膀胱内注入療法の犬における安全性検討
佐々木 東, 青柳 貞一郎, 池中 良徳, 工藤 信樹, 中村 健介, 滝口 満喜, 超音波医学, 48, Suppl., S195, S195, 2021年04月
(公社)日本超音波医学会, 日本語 - Smart Metabolite Databaseを用いたBDE209長期曝露試験によるネコ血清中メタボロームの変動解析
野見山桂, 林多聞, 江口哲史, 水川葉月, 高口倖暉, 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, 環境化学討論会要旨集(CD-ROM), 29th, 2021年 - ネオニコチノイド系農薬クロチアニジンのマウス母乳中移行量に関する定量的評価
正田明日香, 村田碧, 西美咲, 平野哲史, 万谷洋平, 横山俊史, 池中良徳, 星信彦, 日本先天異常学会学術集会プログラム・抄録集, 61st (CD-ROM), 2021年 - ネオニコチノイド系農薬クロチアニジンが次世代マウスの免疫系および腸内細菌叢に及ぼす影響
村田碧, 西美咲, 正田明日香, 池中良徳, 佐伯圭一, 松尾栄子, 平野哲史, 万谷洋平, 横山俊史, 星信彦, 日本先天異常学会学術集会プログラム・抄録集, 61st (CD-ROM), 2021年 - 神経回路形成期におけるステージ別ネオニコチノイド系農薬曝露と発達神経毒性評価
正田明日香, 村田碧, 西美咲, 万谷洋平, 横山俊史, 池中良徳, 平野哲史, 星信彦, 日本獣医学会学術集会講演要旨集, 164th (CD-ROM), 2021年 - ネオニコチノイド系農薬クロチアニジンの胎子・授乳期曝露が次世代マウスの免疫系および腸内細菌叢に及ぼす影響
村田碧, 西美咲, 正田明日香, 佐伯圭一, 松尾栄子, 万谷洋平, 横山俊史, 平野哲史, 池中良徳, 星信彦, 日本獣医学会学術集会講演要旨集, 164th (CD-ROM), 2021年 - 低用量クロチアニジンの神経回路形成期におけるステージ別曝露と発達神経毒性評価
正田明日香, 村田碧, 西美咲, 平野哲史, 万谷洋平, 横山俊史, 池中良徳, 池中良徳, 星信彦, 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 - ネオニコチノイド系農薬クロチアニジンの胎子・授乳期曝露による次世代マウスの免疫系および腸内細菌叢の変化
村田碧, 西美咲, 正田明日香, 池中良徳, 池中良徳, 佐伯圭一, 松尾栄子, 平野哲史, 万谷洋平, 横山俊史, 星信彦, 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 - タンパク質分解系の不均衡状態を介したピレスロイド系農薬による神経毒性の発現機序
平野哲史, 池中良徳, 星信彦, 田渕圭章, 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 - 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 - 超音波と気泡を併用する膀胱内注入療法の犬における安全性検討
佐々木東, 青柳貞一郎, 池中良徳, 工藤信樹, 中村健介, 滝口満喜, 超音波医学 Supplement, 48, 2021年 - 低用量クロチアニジンによる情動変容への加齢の影響評価
宮田結佳, 久保静花, 大野周嗣, 大成果乃子, 前田瑞稀, 中西怜稀, 平野哲史, 万谷洋平, 横山俊史, 石塚真由美, 池中良徳, 星信彦, Endocrine Disrupter News Letter (Web), 22, 4, 2020年 - 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 - 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
日本語 - 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
日本語 - 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
(公社)日本獣医学会, 日本語 - 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
(公社)日本獣医学会, 日本語 - 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
(公社)日本獣医学会, 日本語 - 馬酔木中毒患者の生体試料分析経験
大井真里奈, 丸橋孝昭, 吉村久仁子, 栗原祐太朗, 長田真由子, 池中良徳, 石塚真由美, 浅利靖, 中毒研究, 32, 2, 239, 239, 2019年07月20日
(株)へるす出版, 日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
(一社)日本毒性学会, 日本語 - 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
日本語 - ネオニコチノイド系農薬における野生哺乳動物の曝露状況と都道府県別の出荷量との関連
杉田晄佑, 高田匡, 万谷洋平, 横山俊史, 石塚真由美, 池中良徳, 星信彦, 環境ホルモン学会研究発表会プログラム・要旨集, 22nd (Web), 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 - 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 - 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 - 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。
, 日本毒性学会, 日本語 - 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
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., 日本食品化学学会, 英語 - 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］, ［国際誌］
英語 - 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］, ［国際誌］
英語 - 母子間移行における浸透性農薬およびその代謝産物の定量的な解明
大野周嗣, 大成果乃子, 久保静花, 坂田奈那美, 平野哲史, 万谷洋平, 横山俊史, 石塚真由美, 池中良徳, 星信彦, 日本内分泌かく乱化学物質学会研究発表会要旨集, 21st, 79, 79, 2018年12月
環境ホルモン学会(日本内分泌撹乱化学物質学会), 日本語 - 兵庫県における野生哺乳動物のネオニコチノイド系農薬への曝露実態調査
杉田晄佑, 高田匡, 万谷洋平, 横山俊史, 石塚真由美, 池中良徳, 星信彦, 日本内分泌かく乱化学物質学会研究発表会要旨集, 21st, 82, 2018年12月
日本語 - Linking organochlorine exposure to biomarker response patterns in Anurans: a case study of Müller’s clawed frog (Xenopus muelleri) from a tropical malaria vector control region
Nico J. Wolmarans, Louis H. Du Preez, Louis H. Du Preez, Yared Beyene Yohannes, Yoshinori Ikenaka, Yoshinori Ikenaka, Mayumi Ishizuka, Nico J. Smit, Victor Wepener, Ecotoxicology, 27, 9, 1203, 1216, 2018年11月, ［査読有り］, ［国際誌］
英語 - First report on OH-PAHs in South African Clarias gariepinus bile from an urban impacted system
W. Pheiffer, N. Bortey-Sam, Y. Ikenaka, 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 - 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
日本語 - 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］, ［国際誌］
英語 - 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
日本語, 研究発表ペーパー・要旨（全国大会，その他学術会議） - 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
日本語 - 浸透性農薬とその代謝産物の胎子移行量の解明
大野周嗣, 大成果乃子, 久保静花, 坂田奈那美, 杉田晄佑, 宮田結佳, 高田匡, 平野哲史, 万谷洋平, 横山俊史, 石塚真由美, 池中良徳, 星信彦, 日本獣医学会学術集会講演要旨集, 161st, 467, 467, 2018年08月21日
(公社)日本獣医学会, 日本語 - 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
日本語 - 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
日本語 - Biomarkers in tigerfish (Hydrocynus vittatus) as indicators of metal and organic pollution in ecologically sensitive subtropical rivers
R. Gerber, N. J. Smit, Johan H.J. van Vuren, Y. Ikenaka, Victor Wepener, Ecotoxicology and Environmental Safety, 157, 307, 317, 2018年08月15日
Academic Press, 英語 - 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
<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>, 日本毒性学会, 日本語 - 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
<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>, 日本毒性学会 - 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
<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>, 日本毒性学会 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
(公社)日本獣医学会, 日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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01日
Springer New York LLC, 英語 - 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01日, ［国際誌］
英語 - 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
日本語 - 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］, ［国際誌］
英語 - 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
日本語 - 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。
, 日本毒性学会, 日本語 - 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
日本語 - 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
日本野生動物医学会, 日本語 - 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
日本語 - 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, 池中良徳, 中山翔太, 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, 78, 78, 2017年12月
環境ホルモン学会(日本内分泌撹乱化学物質学会), 日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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］, ［国際誌］
英語 - 北海道・東北地区部会からの報告 : Chemical Hazard Symposiumおよび北海道・東北地区部会会合の報告
池中 良徳, 環境化学 = Journal of environmental chemistry, 27, 3, 98, 100, 2017年09月
日本環境化学会, 日本語 - 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
日本語 - 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
(公社)日本獣医学会, 日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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
日本語 - 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, Journal of Toxicological Sciences, 42, Supplement, S219, 21, 2017年06月
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。
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)
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、in situ 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、in vitro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。
結果・考察：In situ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、in vitro 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in vitro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。, 日本毒性学会, 日本語 - 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, 池中良徳, 中山翔太, 石塚真由美, Journal of Toxicological Sciences, 42, Supplement, S36, 2017年06月
日本語 - 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
日本語 - 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, 池中良徳, 筧麻友, 中山翔太, 石塚真由美, 薬学雑誌, 137, 3, 2017年 - 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
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., 日本毒性学会, 日本語 - 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
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。, 日本毒性学会, 日本語 - 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
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
日本中毒学会 ; 2009-, 日本語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
日本毒性学会, 日本語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
日本語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
日本語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
日本語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 AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT, 34, 11, 1959, 1969, 2017年
英語Insights into the drivers of histopathological changes and potential as bio-indicator of riverine health of an aquatic apex predator from a premier conservation area: A multiple lines of evidence and multivariate statistics approach
R. Gerber, G. M. Wagenaar, W. Smith, Y. Ikenaka, N. J. Smit, ECOLOGICAL INDICATORS, 72, 530, 544, 2017年01月
英語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, 2017年
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.
, 公益社団法人 日本薬学会, 日本語ペットボトル飲料中農薬の分析と食品安全性評価
高本亜希子, 池中良徳, 吉本圭佑, 福島聡, 石塚真由美, 石橋康弘, 有薗幸司, 日本内分泌かく乱化学物質学会研究発表会要旨集, 19th, 76, 76, 2016年12月
環境ホルモン学会(日本内分泌撹乱化学物質学会), 日本語X線照射後のヒト子宮頸がん由来HeLa細胞におけるセミキノンラジカルおよびFe‐SクラスターのESRによる評価
山本久美子, 池中良徳, 一瀬貴大, 石塚真由美, 安井博宣, 平岡和佳子, 鵜飼光子, 山盛徹, 稲波修, 電子スピンサイエンス学会年会講演要旨集, 55th, 156‐157, 2016年11月10日
日本語Novel revelation of warfarin resistant mechanism in roof rats (Rattus rattus) using pharmacokinetic/pharmacodynamic analysis
Kazuki Takeda, Yoshinori Ikenaka, 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］, ［国際誌］
英語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
英語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
日本語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
日本語家畜・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
日本語ヒト子宮頸部がんHeLa細胞における放射線照射後のミトコンドリア応答
稲波修, 山本久美子, 池中良徳, 一瀬貴大, 石塚真由美, 安井博宣, 鵜飼光子, 山盛徹, 日本酸化ストレス学会学術集会プログラム・抄録集, 69th, 142, 2016年08月30日
日本語X線照射したヒト子宮頸がん由来HeLa細胞におけるミトコンドリア機能を中心としたエネルギー代謝応答の解析
山本久美子, 池中良徳, 一瀬貴大, 石塚真由美, 安井博宣, 鵜飼光子, 山盛徹, 稲波修, 日本獣医学会学術集会講演要旨集, 159th, 474, 2016年08月30日
日本語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
日本語LC‐MS/MSによる河川中エクインエストロゲン類の分析
有薗幸司, 石橋弘志, 内田雅也, 吉本圭佑, 山元涼子, 池中良徳, 河合正人, 高尾雄二, 一川暢宏, 冨永伸明, 石橋康弘, 環境化学討論会要旨集(CD-ROM), 25th, ROMBUNNO.P‐075, 2016年06月06日
日本語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
日本語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
日本語長野県諏訪湖における水質と底質の経年変化
宮原裕一, 吉田知可, 一瀬貴大, 池中良徳, 石塚真由美, 環境化学討論会要旨集(CD-ROM), 25th, ROMBUNNO.P‐173, 2016年06月06日
日本語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
日本語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, 2016年06月
日本語ヒト尿中ネオニコチノイドおよびその代謝産物の高感度分析による暴露実態の解明
池中良徳, 石塚真由美, Journal of Toxicological Sciences, 41, Supplement, S150, 3, 2016年06月
近年、ネオニコチノイドによる暴露が原因とされる野生動物、特に鳥類への被害に関する報告が後を絶たない。更に、ネオニコチノイドは、哺乳動物に対して蓄積性はなく、毒性は無視できると言われて来たが、使用量急増による亜急性・慢性曝露の実体、又は健康影響に関する調査はまだまだ不足している。
ここで、ヒトへの曝露実態の解明には非侵襲的に採取できるサンプルである尿がしばしば使用される。即ち、尿中に排泄されるネオニコチノイドおよびその代謝産物を測定することにより曝露量を概算することが可能となる。一方で、ネオニコチノイドは極めて代謝されやすいため、親化合物のみでなく代謝産物も対象としたスクリーニングが必要である。そこで、当該研究では、主要ネオニコチノイド７種（ジノテフラン、ニテンピラム、チアメトキサム、クロチアニジン、イミダクロプリド、アセタミプリド、チアクロプリド）に加え、その代謝産物について一斉分析法を確立し、LC-ESI/MS/MSによる分析を行った。
群馬県の尿サンプルを85検体採取し、分析した結果、ニテンピラム（n = 4）、クロチアニジン（n = 1）、チアメトキサム（n = 7）は親化合物が尿中から検出された。一方、アセタミプリドについて、親化合物は検出されなかったのに対し、その代謝産物であるNデスメチル体が14サンプルで検出された。
当該結果は、ヒトにおけるネオニコチノイドの曝露評価において、代謝産物を含めたスクリーニングが重要である事を示唆するものであった。, 日本毒性学会, 日本語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, 2016年06月
日本語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
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。
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
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。, 日本毒性学会, 日本語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, ［査読有り］
英語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
日本語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
日本語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
日本語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
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。, 日本毒性学会, 日本語ヒト尿中ネオニコチノイドおよびその代謝産物の高感度分析による暴露実態の解明
池中 良徳, 石塚 真由美, 日本毒性学会学術年会, 43, 0, W3, 3, 2016年
近年、ネオニコチノイドによる暴露が原因とされる野生動物、特に鳥類への被害に関する報告が後を絶たない。更に、ネオニコチノイドは、哺乳動物に対して蓄積性はなく、毒性は無視できると言われて来たが、使用量急増による亜急性・慢性曝露の実体、又は健康影響に関する調査はまだまだ不足している。<br>ここで、ヒトへの曝露実態の解明には非侵襲的に採取できるサンプルである尿がしばしば使用される。即ち、尿中に排泄されるネオニコチノイドおよびその代謝産物を測定することにより曝露量を概算することが可能となる。一方で、ネオニコチノイドは極めて代謝されやすいため、親化合物のみでなく代謝産物も対象としたスクリーニングが必要である。そこで、当該研究では、主要ネオニコチノイド７種（ジノテフラン、ニテンピラム、チアメトキサム、クロチアニジン、イミダクロプリド、アセタミプリド、チアクロプリド）に加え、その代謝産物について一斉分析法を確立し、LC-ESI/MS/MSによる分析を行った。<br>群馬県の尿サンプルを85検体採取し、分析した結果、ニテンピラム（n = 4）、クロチアニジン（n = 1）、チアメトキサム（n = 7）は親化合物が尿中から検出された。一方、アセタミプリドについて、親化合物は検出されなかったのに対し、その代謝産物であるNデスメチル体が14サンプルで検出された。<br>当該結果は、ヒトにおけるネオニコチノイドの曝露評価において、代謝産物を含めたスクリーニングが重要である事を示唆するものであった。, 日本毒性学会, 日本語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, 日本毒性学会学術年会, 43, 0, P, 89, 2016年
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。, 日本毒性学会, 日本語UGTの動物種差
石塚 真由美, 中山 翔太, 水川 葉月, 池中 良徳, 日本毒性学会学術年会, 43, 0, S16, 4, 2016年
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。, 日本毒性学会, 日本語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, ワギ ダルウィシュ, 中山 翔太, 水川 葉月, 石塚 真由美, 日本毒性学会学術年会, 43, 0, P, 84, 2016年
【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。, 日本毒性学会, 日本語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
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。, 日本毒性学会, 日本語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
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., 日本毒性学会, 日本語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
日本語第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
日本語渡り性海鳥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
日本語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
日本語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
日本語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
日本語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
日本語出芽酵母発現系を用いたカニクイザル由来UDP‐グルクロン酸転移酵素の異物抱合能の解析
高平梨可, 宇野泰広, 池中良徳, 石塚真由美, 西川美宇, 榊利之, 生城真一, Journal of Toxicological Sciences, 40, Supplement, S187, 25, 2015年06月
【目的】抱合酵素であるUDP-グルクロン酸転移酵素(UGT)は、医薬品、環境汚染物質、食品成分などの生体異物に対するグルクロン酸抱合を触媒する。遺伝子ファミリーを形成しているUGT分子種は、複数の分子種の存在により動物種間において多様な基質及び部位特異性を示す。生体異物に対する毒性評価においてヒト代替動物を用いた代謝解析ではグルクロン酸抱合能に寄与するUGT分子種の機能解析は重要である。本発表では出芽酵母発現系を用いてカニクイザル(Macaca fascicularis, mf)由来UGT分子種の異物抱合能の代謝解析を行った。
【方法】自律複製型発現ベクターpGYRにmfUGT1A分子種のcDNAをそれぞれ組込み、出芽酵母AH22に酢酸リチウム法を用いて遺伝子導入した。それぞれの形質転換体よりミクロソーム膜画分を調製し、ウェスタンブロット法によってタンパク発現を確認した。また、UDP-グルクロン酸供給系との同時発現によるグルクロン酸抱合能を有する酵母株の構築もそれぞれの分子種について行った。種々の基質に対する抱合能解析はC18逆相カラムを用いたHPLCにより分離定量を行った。
【結果・考察】C末端共通領域に対するペプチド抗体を用いたウェスタンブロット解析により、ミクロソーム膜画分およびグルクロン酸抱合能を有する菌体株においてUGT1A分子種の発現を確認した。いずれの分子種もモデル基質であるスコポレチンに対してグルクロン酸抱合能を示し、ビスフェノールAや1-ヒドロキシピレンなどの異物に対しても代謝能が確認された。このことから酵母を用いたin vitroでのUGT抱合能解析が可能であり、抱合体調製系としても有用であることが示された。以上より、出芽酵母発現系を用いたmfUGT分子種の機能解析により、カニクイザルにおけるグルクロン酸抱合能をUGT分子種レベルで理解することが可能となった。, 日本毒性学会, 日本語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, 2015年06月
日本語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
英語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
日本語カニクイザル由来UDP‐グルクロン酸転移酵素におけるポリフェノール類代謝能の解析
高平梨可, 西川美宇, 宇野泰広, 池中良徳, 石塚真由美, 榊利之, 生城真一, 日本農芸化学会大会講演要旨集(Web), 2015, 2F22P02 (WEB ONLY), 2015年03月05日
日本語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
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., 日本毒性学会, 日本語Phase II酵素の欠損動物と非欠損動物 ー新たな動物種マッピングー
池中 良徳, Aksorn SAENGTIENCHAI, 筧 麻友, Wageh Sobhy, DARWISH, 水川 葉月, 中山 翔太, 石塚 真由美, 日本毒性学会学術年会, 42, 0, S9, 3, 2015年
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。, 日本毒性学会, 日本語出芽酵母発現系を用いたカニクイザル由来UDP-グルクロン酸転移酵素の異物抱合能の解析
高平 梨可, 宇野 泰広, 池中 良徳, 石塚 真由美, 西川 美宇, 榊 利之, 生城 真一, 日本毒性学会学術年会, 42, 0, O, 25, 2015年
【目的】抱合酵素であるUDP-グルクロン酸転移酵素(UGT)は、医薬品、環境汚染物質、食品成分などの生体異物に対するグルクロン酸抱合を触媒する。遺伝子ファミリーを形成しているUGT分子種は、複数の分子種の存在により動物種間において多様な基質及び部位特異性を示す。生体異物に対する毒性評価においてヒト代替動物を用いた代謝解析ではグルクロン酸抱合能に寄与するUGT分子種の機能解析は重要である。本発表では出芽酵母発現系を用いてカニクイザル(<i>Macaca fascicularis</i>, mf)由来UGT分子種の異物抱合能の代謝解析を行った。<br>【方法】自律複製型発現ベクターpGYRにmfUGT1A分子種のcDNAをそれぞれ組込み、出芽酵母AH22に酢酸リチウム法を用いて遺伝子導入した。それぞれの形質転換体よりミクロソーム膜画分を調製し、ウェスタンブロット法によってタンパク発現を確認した。また、UDP-グルクロン酸供給系との同時発現によるグルクロン酸抱合能を有する酵母株の構築もそれぞれの分子種について行った。種々の基質に対する抱合能解析はC18逆相カラムを用いたHPLCにより分離定量を行った。<br>【結果・考察】C末端共通領域に対するペプチド抗体を用いたウェスタンブロット解析により、ミクロソーム膜画分およびグルクロン酸抱合能を有する菌体株においてUGT1A分子種の発現を確認した。いずれの分子種もモデル基質であるスコポレチンに対してグルクロン酸抱合能を示し、ビスフェノールAや1-ヒドロキシピレンなどの異物に対しても代謝能が確認された。このことから酵母を用いたin vitroでのUGT抱合能解析が可能であり、抱合体調製系としても有用であることが示された。以上より、出芽酵母発現系を用いたmfUGT分子種の機能解析により、カニクイザルにおけるグルクロン酸抱合能をUGT分子種レベルで理解することが可能となった。, 日本毒性学会, 日本語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日尿中ネオニコチノイド6種類/代謝産物一斉分析による一般人の前向き研究
平久美子, MARFO Jemima, 池中良徳, 藤岡一俊, 青山美子, 日本公衆衛生学会総会抄録集, 73rd, 268, 2014年10月15日
日本語金粒子含有ナノゲルによる小胞体ストレスを介した放射線増感作用
安井博宣, 武内亮, 永根大幹, 山盛徹, 池中良徳, 昆泰寛, 室谷憲紀, 大石基, 長崎幸夫, 稲波修, 日本放射線影響学会大会講演要旨集, 57th, 109, 2014年09月17日
日本語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
日本語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
日本語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
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。, 日本毒性学会, 日本語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
【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（<sup>207</sup>Pb/<sup>206</sup>Pb、<sup>208</sup>Pb/<sup>206</sup>Pb）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。, 日本毒性学会, 日本語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, 78, 2014年07月
【目的】グルクロン酸抱合酵素(UGT)は、生体外異物代謝の第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(Feliformia)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、この偽遺伝子化に伴いアセトアミノフェン等の薬物の毒性作用が強いことが知られている。一方、食肉目に属する鰭脚類(Pinnipedia)では、環境化学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についての研究は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、肝臓でのUGT活性の測定と系統解析を行った。<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作成し、1-ヒドロキシピレン(UGT1A6、UGT1A7、UGT1A9)、アセトアミノフェン(UGT1A1、UGT1A6、UGT1A9)、セロトニン(UGT1A6)を基質としてUGT活性を測定した。また、NCBIのデータベースからUGT1A領域の系統解析およびシンテニー解析を行った。<br>【結果及び考察】1-ヒドロキシピレン、アセトアミノフェン、セロトニンに対するUGT抱合活性を測定した結果、ラットに比べ食肉目では極めて低い活性を示した。また、系統解析及びシンテニー解析より、解析した全ての食肉目において、UGT1A分子種は特徴的な2遺伝子であるUSP40 とMROH2の間に保存されていることが明らかになった。さらに、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。以上の結果から、鰭脚類を含めた食肉目は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。, 日本毒性学会, 日本語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
【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。, 日本毒性学会, 日本語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
日本語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
日本語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
日本語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
日本語出芽酵母発現系を用いたカニクイザル由来UDP‐グルクロン酸転移酵素の機能解析
高平梨可, 宇野泰広, 池中良徳, 石塚真由美, 西川美宇, 榊利之, 生城真一, 日本生化学会大会(Web), 87th, 3P-182 (WEB ONLY), 2014年
日本語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
日本語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
日本語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
日本語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
日本語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
英語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
日本語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
日本語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
日本語【人と動物の共通感染症最前線10】日本のげっ歯類におけるハンタウイルス感染の血清疫学調査とエゾヤチネズミが保有するHokkaidoウイルスの分離
苅和 宏明, 尾崎 由佳, 真田 崇弘, 池中 良徳, 石塚 真由美, 坪田 敏男, 好井 健太朗, 吉松 組子, 有川 二郎, 高島 郁夫, 獣医畜産新報, 66, 4, 262, 264, 2013年04月
文永堂出版(株), 日本語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
日本語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
日本語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
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 μg/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., 日本毒性学会, 英語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
<b>[Introduction]</b> <br> In our previous work, positive correlations between CYP1A- dependent activities, protein expression and β-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 µM) 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, β-carotene differentially modulated AhR gene battery., 日本毒性学会, 英語鳥類における薬物代謝の特徴:ビレンをモデル化合物として
河田みなみ, 池中良徳, 渡邉研右, AKSORN Saengtienchai, 大野円実, 石塚真由美, 日本獣医学会学術集会講演要旨集, 154th, 349, 2012年08月31日
日本語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
英語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
英語薬物代謝第II相抱合反応の種差:多環芳香族炭化水素の抱合反応と哺乳動物で観察された種差
池中良徳, SAENGTIENCHAI Aksorn, 川合佑典, 石塚真由美, 環境化学討論会要旨集(CD−ROM), 21st, ROMBUNNO.1D-10, 2012年07月10日
日本語両棲類の異物代謝機構の特徴と種差
池中良徳, 上田春樹, SAENGTIENCHAI Aksorn, 石塚真由美, 環境化学討論会要旨集(CD−ROM), 21st, ROMBUNNO.P-210, 2012年07月10日
日本語鳥類における異物代謝反応:第I相および第II相反応の特徴と種差
池中良徳, 河田みなみ, 渡辺研右, SAENGTIENCHAI Aksorn, 大野円美, 石塚真由美, 環境化学討論会要旨集(CD−ROM), 21st, ROMBUNNO.P-211, 2012年07月10日
日本語魚類における異物代謝機構の特徴と種差:多環芳香族炭化水素(PAH)に対する生体防御
小栗真美, 池中良徳, SAENGTIENCHAI Aksorn, 石塚真由美, 環境化学討論会要旨集(CD−ROM), 21st, ROMBUNNO.3C-04, 2012年07月10日
日本語鳥類異物代謝における重要なCYP分子種の特定とその種差の解明
渡邉研右, 河田みなみ, 川合佑典, 池中良徳, 石塚真由美, J Toxicol Sci, 37, Supplement 1, S238, 163, 2012年07月
【背景と目的】鳥類では、ミクロソームを用いたシトクロムP450（CYP）によるワルファリン代謝活性について、ニワトリと比べ他種鳥類では活性が低く、数十倍の種差があることが明らかになっている。しかし、これまでにゲノムプロジェクトが終了しているニワトリにおいてもCYP分子種ごとの発現解析や機能解析が行われておらず、異物代謝上重要と考えられる分子種やそれぞれの機能が明らかになっていない。そのため、これまでに報告されている鳥類種間での異物代謝能の種差が、どの分子種に帰属されるのかも明らかでない。そこで、本研究では、鳥類の異物代謝において重要と考えられる分子種の特定と、その種差を明らかにすることを目的とした。【方法と結果】ニワトリの肝臓を用い、CYP分子種ごとのmRNAコピー数を比較したところ、肝臓においてCYP1A5、2C23、2C45が多く発現していることが明らかになった。一方で、ニワトリなどの家禽で研究が進められているCYP3A37は大きな発現量を示さなかった。また、哺乳類でCYP2Bや3Aを誘導するフェノバルビタールを投与した場合においても、CYP2C、3Aが受ける誘導は同程度だった。そこで、これまでに機能解析がほとんど行われていないCYP2C23について8種の鳥類からcDNAクローニングを行い、鳥類種間で保存されているアミノ酸領域に対する抗ペプチド抗体の作製を行った。各鳥類種の肝臓ミクロソームについて、この抗体を用いたウェスタンブロット法を行った結果、すべての鳥類種でCYP2C23特異的に交差反応が見られ、CYP2C23タンパク質を定量することができた。【考察】mRNAコピー数比較から、鳥類ではCYP2Cサブファミリーが多く発現し、重要な分子種であると考えられた。そこで、鳥類CYP2C23特異的抗体を用いたタンパク質発現量比較を行ったが、その発現量には大きな種差が見られなかった。以上の結果より、鳥類種間で見られる活性の種差はタンパク質発現量の違いによるものではなく、酵素の機能的な違いによるものであると考えられた。, 日本毒性学会, 日本語クマネズミの環境適応戦略と日本におけるスーパーラットの分布
新海秀史, 春成常仁, 田中和之, 谷川力, 池中良徳, 石塚真由美, 生理学技術研究会報告, 2012, 34, 57-59, 59, 2012年06月25日
日本語The genetic mechanisms of warfarin resistance in Rattus rattus found in the wild in Japan
Kazuyuki D. Tanaka, Yusuke K. Kawai, Yoshinori Ikenaka, Tsunehito Harunari, Tsutomu Tanikawa, Shima Ando, Hee Won Min, Fumie Okajima, Shoichi Fujita, Mayumi Ishizuka, PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY, 103, 2, 144, 151, 2012年06月
英語Molecular cloning and characterization of Th1 and Th2 cytokines of African buffalo (Syncerus caffer)
S. Suzuki, S. Konnai, T. Okagawa, N. W. Githaka, E. Kariuki, F. Gakuya, E. Kanduma, T. Shirai, R. Ikebuchi, Y. Ikenaka, M. Ishizuka, S. Murata, K. Ohashi, INTERNATIONAL JOURNAL OF IMMUNOGENETICS, 39, 2, 170, 182, 2012年04月
英語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
日本語鳥類におけるI相およびII相反応の特徴と種差
河田みなみ, 池中良徳, 渡邉研右, 大野円実, 上田春樹, 西山義広, 石塚真由美, 日本獣医学会学術集会講演要旨集, 153rd, 265, 2012年03月01日
日本語Molecular evidence predicts aryl hydrocarbon receptor ligand insensitivity in the peregrine falcon (Falco peregrines)
Nozomi Fujisawa, Yoshinori Ikenaka, Eun-Young Kim, Jin-Seon Lee, Hisato Iwata, Mayumi Ishizuka, EUROPEAN JOURNAL OF WILDLIFE RESEARCH, 58, 1, 167, 175, 2012年02月
英語ダチョウ肝臓に発現する異物代謝酵素の配列解析
川合佑典, 渡邉研右, 石井秋宏, 大沼愛子, 澤洋文, 池中良徳, 石塚真由美, 日本進化学会大会プログラム・講演要旨集(Web), 14th, 2012年Astaxanthin rich crude extract of Haematococcus pluvialis induces cytochrome P450 1A1 mRNA by activating aryl hydrocarbon receptor in rat hepatoma H4IIE cells
Marumi Ohno, Wageh Sobhy Darwish, Yoshinori Ikenaka, Wataru Miki, Shoichi Fujita, Mayumi Ishizuka, FOOD CHEMISTRY, 130, 2, 356, 361, 2012年01月
英語Comparative metabolism of warfarin in rats and chickens
A. Saengtienchai, Y. Ikenaka, K. Watanabe, T. Ishida, M. Ishizuka, POULTRY SCIENCE, 90, 12, 2775, 2781, 2011年12月
英語北海道におけるタンチョウの水銀汚染の原因についての検討
岡本絵梨佳, 久道萌, 水野直治, 古賀公也, 志村良治, 中山翔, 池中良徳, 石塚真由美, 北澤多喜雄, 井上雅子, 百瀬邦和, 正富宏之, 寺岡宏樹, 日本鳥学会大会講演要旨集, 2011, 63, 2011年09月13日
日本語北海道におけるタンチョウの水銀汚染の原因についての検討
岡本絵梨佳, 久道萌, 水野直治, 古賀公也, 志村良治, 中山翔, 池中良徳, 石塚真由美, 北澤多喜雄, 井上雅子, 百瀬邦和, 正富宏之, 寺岡宏樹, 寺岡宏樹, 日本鳥学会大会講演要旨集, 2011, 63, 2011年09月13日
日本語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
日本語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
日本語日本のげっ歯類のハンタウイルス感染状況に関する血清疫学調査とエゾヤチネズミが保有するHokkaidoウイルスの遺伝的多様性
尾崎 由佳, 萩谷 友洋, 真田 崇弘, 瀬戸 隆弘, Taylor Kyle, 吉川 佳佑, Ivanov Leonid I., 好井 健太朗, 坪田 敏男, 池中 良徳, 石塚 真由美, 吉松 組子, 有川 二郎, 苅和 宏明, 北海道獣医師会雑誌, 55, 8, 415, 415, 2011年08月
(公社)北海道獣医師会, 日本語日本のげっ歯類のハンタウイルス感染状況に関する血清疫学調査とエゾヤチネズミが保有するHokkaidoウイルスの遺伝的多様性
尾崎 由佳, 萩谷 友洋, 真田 崇弘, 瀬戸 隆弘, Kyle Taylor, 吉川 佳佑, Leonid Ivanov, 好井 健太朗, 坪田 敏男, 池中 良徳, 石塚 真由美, 吉松 組子, 有川 二郎, 苅和 宏明, 日本獣医学会学術集会講演要旨集, 152回, 256, 256, 2011年08月
(公社)日本獣医学会, 日本語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
英語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
英語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
日本語Furazolidone induces the activity of microsomal enzymes that metabolize furazolidone in chickens
Nobuo Sasaki, Tomoyuki Matsumoto, Yoshinori Ikenaka, Akio Kazusaka, Mayumi Ishizuka, Shoichi Fujita, PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY, 100, 2, 135, 139, 2011年06月
英語多環芳香族炭化水素類(PAHs)に対する魚類の異物代謝機構の解明:魚類で観察された第II相抱合反応の特徴と種差
小栗真美, 池中良徳, AKSORN Saengtienchai, 上田春樹, 石塚真由美, J Toxicol Sci, 36, Supplement, S119, 2011年06月
日本語野生動物の化学物質感受性と生体防御機構
池中 良徳, 石塚 真由美, 安全工学, 50, 2, 80, 84, 2011年04月15日
<p>野生動物は環境化学物質に汚染された環境下で棲息をしており，常にこれらの化学物質に曝露されている．本節では，野生動物の化学物質感受性と生体防御機構について，外来化学物質を代謝する主要酵素シトクロムP450 を中心に概説する．また，汚染環境下で棲息する野生の動物が，環境に適応する為にどのような変化を示すのか，野生のドブネズミを例に最近の研究を報告する．</p>, 安全工学会, 日本語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
日本語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
日本語野生げっ歯類におけるワルファリン抵抗性機構と遺伝的背景
田中和之, 春成常仁, 谷川力, 渡邉研右, 池中良徳, 石塚真由美, 日本獣医師会獣医学術学会年次大会講演要旨集, 2010, 170, 2011年01月31日
日本語High expression of the mRNA of cytochrome P450 and phase II enzymes in the lung and kidney tissues of cattle
W. S. Darwish, Y. Ikenaka, W. R. El-Ghareeb, M. Ishizuka, ANIMAL, 4, 12, 2023, 2029, 2010年12月
英語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
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., Academic Journals, 英語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
日本語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
日本語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
日本語野生げっ歯類におけるワルファリン抵抗性機構と遺伝的背景について
田中和之, 春成常仁, 谷川力, 川合佑典, 渡邉研右, バラージュ オロスラーニュ, 池中良徳, 石塚真由美, 北海道獣医師会雑誌, 54, 8, 478, 2010年08月10日
日本語芳香族炭化水素受容体(AhR)の分子生物学的解析による鳥類のダイオキシン類感受性評価
藤澤希望, 池中良徳, 山本秀明, KIM Eun‐Young, LEE Jin‐Seon, 岩田久人, 石塚真由美, 北海道獣医師会雑誌, 54, 8, 477, 2010年08月10日
日本語Mutagenic activation and detoxification of benzo[a]pyrene in vitro by hepatic cytochrome P450 1A1 and phase II enzymes in three meat-producing animals
W. Darwish, Y. Ikenaka, E. Eldaly, M. Ishizuka, FOOD AND CHEMICAL TOXICOLOGY, 48, 8-9, 2526, 2531, 2010年08月
英語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
英語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
日本語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
日本語芳香族炭化水素受容体(AhR)の分子生物学的解析による鳥類のダイオキシン類感受性評価
藤澤希望, 池中良徳, 山本秀明, KIM Eun‐Young, LEE Jin‐Seon, 岩田久人, 石塚真由美, J Toxicol Sci, 35, Supplement, S132, 2010年05月
日本語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, 2010年05月
日本語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
日本語国内におけるワルファリン抵抗性ネズミの現況:いわゆるスーパーラットについて
田中 和之, 常仁 春成, 谷川 力, 池中 良徳, 石塚 真由美, 環境毒性学会誌, 12, 2, 61, 70, 2009年12月30日
Warfarin is commonly used worldwide as a rodenticide. Warfarin inhibits blood coagulation, and continuous intake of warfarin causes potentially fatal hemorrhages. However, warfarin-resistant roof rats（Rattus rattus）are found in Japan, especially in the Tokyo area. Recently, warfarin-resistant brown rats（Rattus norvegicus）were discovered in rural areas of Japan. Warfarin-resistant house mice have not been reported, but it is highly possible that resistant mice will be also found in our country. Warfarin-resistant rats, which have acquired resistance to anticoagulant rodenticides, are called &ｌquot;super rats&ｒquot;. Rodenticide-resistant roof rats, brown rats, and house mice have been also reported in the United States and European countries, e.g., Britain, France, Denmark, and Germany. In addition, warfarin-resistant rodents may be widespread in other countries that have not been investigated yet. The warfarin target molecule is vitamin K epoxide reductase（VKOR）．Warfarin inhibits the function of VKOR, which recycles vitamin K to activate blood coagulant factors, and causes hemorrhage. Substitutions in the VKORC1 gene were reported in warfarin-resistant rodents. Moreover, the metabolism of warfarin is accelerated in warfarin-resistant rats due to the elevation of cytochrome P450-dependent xenobiotic metabolizing activities. The combination of a VKOR mutation and P450 acceleration causes warfarin resistance in wild rodents, which is an evolutionary adaptation to the pesticide-polluted environment. After the appearance of warfarin-resistant rodents, a second-generation rodenticide was developed and replaced warfarin in Europe and America. In Japan, difethialone is the only the second-generation rodenticide that can be used in public buildings. In Japan, a critical zoonosis infection has not yet spread on a large scale through wild rodents. However, it is necessary to consider how to prevent serious infestation by house rodents in the industrial, administrative, and academic sectors before such infestation occurs., 日本環境毒性学会, 日本語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
英語諏訪湖に生息する生物の多環芳香族炭化水素類汚染とその蓄積特性
池中 良徳, 伊藤 有希, 殷 煕洙, 渡邉 栄喜, 宮原 裕一, 環境化学 : journal of environmental chemistry, 18, 3, 341, 352, 2008年09月24日
The purpose of the present study was to elucidate the characteristic accumulation patterns of the Polycyclic Aromatic Hydrocarbons (PAHs) in various organisms inhabited in the typical eutrophic lake "Lake Suwa". We also calculated the Biota Sediment Accumulation Factors (BSAF) of each organism to estimate the difference in the pattern of PAHs accumulation among their tropic levels or habitat.<BR>We showed that the concentrations of Σ<SUB>11</SUB>PAHs was highest in phytoplankton (mainly Aphanizomenon sp.) (36,900±2,800 ng/g-lipid), followed by chironomid (3, 130±380 ng/g-lipid), catfish (1,720±1,360 ng/g-lipid), zooplankton (mainly Bosmina sp.) (890±170 ng/g-lipid), cherry salmon (270±70 ng/g-lipid), freshwater prawn (240±70 ng/g-lipid), largemouth bass(130±20 ng/g-lipid), Japanese smelt (140±30 ng/g-lipid), crucian carp (120±4 ng/g-lipid), and common carp (50±16 ng/g-lipid). We also analyzed dioxins (DXNs) in largemouth bass.The concentration of polychlorinated dibenzo-<I>p</I>-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), non-<I>ortho</I> dioxin like-PCBs, and mono-<I>ortho</I>-substituted dioxin-like PCBs (dioxin-like PCBs) were 7±1, 3±1, 117±13 ,and 3,770±930 ng/g-lipid, respectively. Based on these data, we calculated the BSAF of each organism. Σ<SUB>11</SUB>PAHs BSAF exceeded 1.0 only in phytoplankton (18.7 g-ignition loss/g-lipid) and chironomid (1.6 g-ignition loss/g-lipid), and other organisms, especially fish, were below 1.0. These results indicated that PAHs were the substances mainly accumulated in primary consumers but not in higher tropic level consumers. On the other hand, BSAF of PAHs and dioxin like-PCBs in largemouth bass had large difference. This may due to the high metabolic rate of PAHs compared to dioxin like-PCBs. These results indicated that ability to metabolize PAHs is important to estimate accumulation pattern of PAHs.<BR>From our results, different accumulation pattern of PAHs in invertebrate and fish were observed. Invertebrates accumulate high Kow PAHs compared to fish. These results may also due to the difference in the ability to metabolize PAHs between fish and invertebrates., 日本環境化学会, 日本語抗菌剤フラゾリドンによるラット肝臓のCYP1A1誘導(毒性学)
佐々木 信夫, 酒井 紀彰, 池中 良徳, 神谷 知未, 閔 姫源, 坂本 健太郎, 石塚 真由美, 藤田 正一, The journal of veterinary medical science, 70, 3, 223, 226, 2008年03月
英語諏訪湖に生息する生物の多環芳香族炭化水素類汚染とその蓄積特性
池中 良徳, 伊藤 有希, 殷 煕洙, 渡邉 栄喜, 宮原 裕一, Journal of Environmental Chemistry, 18, 3, 341, 352, 2008年
The purpose of the present study was to elucidate the characteristic accumulation patterns of the Polycyclic Aromatic Hydrocarbons (PAHs) in various organisms inhabited in the typical eutrophic lake "Lake Suwa". We also calculated the Biota Sediment Accumulation Factors (BSAF) of each organism to estimate the difference in the pattern of PAHs accumulation among their tropic levels or habitat.<BR>We showed that the concentrations of Σ<SUB>11</SUB>PAHs was highest in phytoplankton (mainly Aphanizomenon sp.) (36,900±2,800 ng/g-lipid), followed by chironomid (3, 130±380 ng/g-lipid), catfish (1,720±1,360 ng/g-lipid), zooplankton (mainly Bosmina sp.) (890±170 ng/g-lipid), cherry salmon (270±70 ng/g-lipid), freshwater prawn (240±70 ng/g-lipid), largemouth bass(130±20 ng/g-lipid), Japanese smelt (140±30 ng/g-lipid), crucian carp (120±4 ng/g-lipid), and common carp (50±16 ng/g-lipid). We also analyzed dioxins (DXNs) in largemouth bass.The concentration of polychlorinated dibenzo-<I>p</I>-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), non-<I>ortho</I> dioxin like-PCBs, and mono-<I>ortho</I>-substituted dioxin-like PCBs (dioxin-like PCBs) were 7±1, 3±1, 117±13 ,and 3,770±930 ng/g-lipid, respectively. Based on these data, we calculated the BSAF of each organism. Σ<SUB>11</SUB>PAHs BSAF exceeded 1.0 only in phytoplankton (18.7 g-ignition loss/g-lipid) and chironomid (1.6 g-ignition loss/g-lipid), and other organisms, especially fish, were below 1.0. These results indicated that PAHs were the substances mainly accumulated in primary consumers but not in higher tropic level consumers. On the other hand, BSAF of PAHs and dioxin like-PCBs in largemouth bass had large difference. This may due to the high metabolic rate of PAHs compared to dioxin like-PCBs. These results indicated that ability to metabolize PAHs is important to estimate accumulation pattern of PAHs.<BR>From our results, different accumulation pattern of PAHs in invertebrate and fish were observed. Invertebrates accumulate high Kow PAHs compared to fish. These results may also due to the difference in the ability to metabolize PAHs between fish and invertebrates., Japan Society for Environmental Chemistry, 日本語諏訪湖における多環芳香族炭化水素類の年間収支の推定
宮原 裕一, 池中 良徳, 環境化学 : journal of environmental chemistry, 17, 4, 649, 658, 2007年12月25日
In the present study, we estimated inflow and effluent load of Polycyclic Aromatic Hydrocarbons (PAHs) in Lake Suwa, Japan. Estimation of PAHs inflow and effluent load were performed by measuring changes in stream flow and concentration of suspended solids (SS) in the lake and river water. Results showed that the concentration of SS increased with stream flow. Annual (March 2004 to February 2005) inflow and effluent load of SS at the lake were calculated as 8.9×10<sup>6</sup> kg and 7.6×10<sup>6</sup> kg, respectively. The mass balance between inflow and effluent load indicated that 1.3×10<sup>6</sup> kg of SS were sedimentated to the lake. The total amount of Σ<sub>9</sub>PAHs (Phenanthrene, Pyrene, Chrysene, Benzo[e]pyrene, Benzo[b]fluoranthene, Benzo[k]fluoranthene, Benzo[a]pyrene, Dibenz[a,h]anthracene, Benzo[ghi]perylene) in lake SS varied by 230±120 g/lake (average±SD); the maximum amount exceeded 500 g/lake, which was observed in May and October 2004. Specifically, for Benzo[a]pyrene the total amount in lake SS was 14±7 g/lake. Estimation of total Σ<sub>9</sub>PAHs flowing into Lake Suwa and out through Kamaguchi Gate indicated Σ<sub>9</sub>PAHs values of 8.6 and 3.5 kg/yr, respectively. The mass balance between Σ<sub>9</sub>PAHs inflow and outflow indicated that approximately 5.1 kg/yr of Σ<sub>9</sub>PAHs were sedimentated with SS to the lake. The annual flux of PAHs in Lake Suwa calculated in the present study agreed with the deposition flux of PAHs in a previous study estimated from sediment cores (4 kg/yr) (Ikenaka et al.: Environ. Pollut., 138, 530-538 (2005)). Inflow loads of PAHs markedly increased in May 21, October 9, and October 21 when heavy rains occurred, occupying approximately 27 % of the annual inflow. These results indicated that large quantities of PAHs flowed into the lake when river flow increased by heavy rain., 日本環境化学会, 日本語水棲甲殻類によるPAHs代謝機構の解明:Pyreneの代謝反応と新規抱合体の構造推定
池中良徳, EUN Heesoo, 石坂真澄, 宮原裕一, 環境化学討論会講演要旨集, 16th, 650, 651, 2007年06月19日
日本語諏訪湖における多環芳香族炭化水素類の年間収支の推定
宮原 裕一, 池中 良徳, Journal of Environmental Chemistry, 17, 4, 649, 658, 2007年
In the present study, we estimated inflow and effluent load of Polycyclic Aromatic Hydrocarbons (PAHs) in Lake Suwa, Japan. Estimation of PAHs inflow and effluent load were performed by measuring changes in stream flow and concentration of suspended solids (SS) in the lake and river water. Results showed that the concentration of SS increased with stream flow. Annual (March 2004 to February 2005) inflow and effluent load of SS at the lake were calculated as 8.9×106 kg and 7.6×106 kg, respectively. The mass balance between inflow and effluent load indicated that 1.3×106 kg of SS were sedimentated to the lake. The total amount of Σ9PAHs (Phenanthrene, Pyrene, Chrysene, Benzo[e]pyrene, Benzo[b]fluoranthene, Benzo[k]fluoranthene, Benzo[a]pyrene, Dibenz[a,h]anthracene, Benzo[ghi]perylene) in lake SS varied by 230±120 g/lake (average±SD); the maximum amount exceeded 500 g/lake, which was observed in May and October 2004. Specifically, for Benzo[a]pyrene the total amount in lake SS was 14±7 g/lake. Estimation of total Σ9PAHs flowing into Lake Suwa and out through Kamaguchi Gate indicated Σ9PAHs values of 8.6 and 3.5 kg/yr, respectively. The mass balance between Σ9PAHs inflow and outflow indicated that approximately 5.1 kg/yr of Σ9PAHs were sedimentated with SS to the lake. The annual flux of PAHs in Lake Suwa calculated in the present study agreed with the deposition flux of PAHs in a previous study estimated from sediment cores (4 kg/yr) (Ikenaka et al.: Environ. Pollut., 138, 530-538 (2005)). Inflow loads of PAHs markedly increased in May 21, October 9, and October 21 when heavy rains occurred, occupying approximately 27 % of the annual inflow. These results indicated that large quantities of PAHs flowed into the lake when river flow increased by heavy rain., Japan Society for Environmental Chemistry, 日本語諏訪湖における多環芳香族炭化水素類汚染の特徴とその集水域との関係
池中 良徳, 館野 覚俊, 宮原 裕一, Journal of Environmental Chemistry, 17, 2, 217, 226, 2007年
In the present study, we investigated the Polycyclic Aromatic Hydrocarbons (PAHs) at the representative eutrophic lake "Lake Suwa", which has drastically eutrophicated since 1960s by inflow of domestic and industrial effluents. We also investigated PAHs in river sediments, road dusts, suspended solids and air particles of the catchment area of Lake Suwa.We showed that the concentrations of Σ17PAHs in the lake sediments and river sediments were 364±129 ng/g-dry and 157±194 ng/g-dry, respectively. On the other hand, the concentrations of Σ17PAHs in sediments were relatively high in the northeast part of Lake Suwa.One of the major PAHs in the sediment of Lake Suwa was perylene. It would be mainly produced from precursor substances (such as perylenequinone) in anoxic lake sediment. On the other hand, the major sources of other PAHs (except perylene) were considered to be both petrogenic and pyrogenic source as diesel exhaust matter and asphalt. They entered the Lake Suwa through rivers and finally precipitated to lake sediment., Japan Society for Environmental Chemistry, 日本語動物プランクトン群集内で観察されるケミカルコミュニケーションの重要性:殺虫剤投与による生物間相互作用の撹乱と群集構造への影響
坂本正樹, 花里孝幸, 池中良徳, 宮原裕一, 日本陸水学会大会講演要旨集, 71st, 0, 138, 4, 2006年09月05日
日本陸水学会, 日本語Daphnia magnaによるＰｙｒｅｎｅの代謝反応：Ｐｙｒｅｎｅ代謝経路と第一相、第二相代謝酵素群の解明
池中 良徳, 石坂 真澄, 殷 熙洙, 宮原 裕一, 日本陸水学会 講演要旨集, 71, 0, 6, 6, 2006年
日本陸水学会, 日本語ミジンコ(Daphnia magna)が持つ薬物代謝酵素群の解明
池中良徳, 石塚真由美, 藤田正一, 坂本健太郎, 渡邉肇, 宮原裕一, 日本陸水学会甲信越支部会報, 31, 57, 2005年12月
日本語Sources, distribution, and inflow pattern of dioxins in the bottom sediment of lake Suwa, Japan
Y Ikenaka, H Eun, E Watanabe, Y Miyabara, BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY, 75, 5, 915, 921, 2005年11月
英語動物プランクトンによるPAHsの代謝能および代謝産物の解明‐Daphnia magnaによるPyreneの代謝‐
池中良徳, 石坂真澄, EUN Heesoo, 宮原裕一, 環境化学討論会講演要旨集, 14th, 288, 289, 2005年06月15日
日本語湖底堆積物からみた諏訪湖における汚染物質の集積過程
公文 富士夫, 池中 良徳, 第14回環境地質学シンポジウム論文集, 14th, 323, 328, 2004年12月06日
Sedimentation of Lake Suwa is much affected by flood sediments even in the center of the lake. The concentrations of dioxins and PAHs are diluted by such event sediment composed mainly of inorganic,non-contaminated materials. Flood sediment layers dated on 10 June 1950, 29 June 1961 and 28 September 1983 are confirmed in the cored sediments from Lake Suwa. Although the persistent organic pollutants are low in the floodsediments compared with the normal sediments below and above, the total amount of pollutants deposited in one flood is much larger than the annual amount of normal sediments...., 地質汚染－医療地質－社会地質学会, 日本語諏訪湖底質柱状試料から見たダイオキシン類,多環芳香族炭化水素類の発生源に関する研究
池中良徳, 渡辺栄喜, EUN H, 宮原裕一, 環境化学討論会講演要旨集, 13th, 162, 163, 2004年07月05日
日本語諏訪湖における多環芳香族炭化水素類の分布
宮原裕一, 池中良徳, 犬塚良平, 上沢春香, 牛原阿海, 笠井由香, 角田紗代子, 日本内分泌かく乱化学物質学会研究発表会要旨集, 6th, 149, 2003年12月02日
日本語共同研究・競争的資金等の研究課題
- 父性曝露影響から捉える農薬の継世代影響評価・エピゲノム毒性
科学研究費助成事業
2025年04月01日 - 2028年03月31日
星 信彦, 池中 良徳, 平野 哲史, 横山 俊史
日本学術振興会, 基盤研究(B), 神戸大学, 25K03271 - 魚類を指標とした発生・中枢神経毒性を示す新規・未規制医薬品類の探索
科学研究費助成事業
2024年04月01日 - 2028年03月31日
野見山 桂, 岩田 久人, 池中 良徳, 久保田 彰, 田上 瑠美, 江口 哲史
日本学術振興会, 基盤研究(A), 愛媛大学, 24H00779 - 脳機能撹乱検出法・診断法の開発を起点としたシグナル毒性評価プラットフォームの創設
科学研究費助成事業 基盤研究(A)
2023年04月01日 - 2027年03月31日
池中 良徳
日本学術振興会, 基盤研究(A), 北海道大学, 23H00512 - グリアーニューロン連関の撹乱から迫る化学物質による神経毒性の上流メカニズムの探索
科学研究費助成事業
2024年06月28日 - 2026年03月31日
平野 哲史, 星 信彦, 池中 良徳
日本学術振興会, 挑戦的研究(萌芽), 富山大学, 24K22204 - 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
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))
2022年10月07日 - 2026年03月31日
石塚 真由美, 武田 一貴, 池中 良徳, 江口 哲史, 中山 翔太
環境汚染により年間 900 万人が死亡しており、これは戦争やマラリアを抜いて、世界の早期死因 の 1/6 の原因になったことが報告された。環境汚染による早期死亡の多くは途上国で起こっており、特にアフリカは地球上で急激に環境が汚染され、世界的にも極めて多くの早期死亡者と経済 的損失を生み出している地域となった。一方、環境汚染の毒性には様々な作用があることが細胞 や動物実験から報告されているが、疫学的調査やフォール度の事象としてはとらえきれないもの が多い。我々は、重度に化学物質に汚染されたアフリカにおいてフィールドベースで毒性学的研究を展開し、ヒトおよびその生活圏に棲息するシナントロープ動物の双方から研究を進めるフィー ルド Zoobiquity（汎動物学）を実施する。本研究により、何世代にも及ぶ長期にわたる化学物質の 高濃度曝露により、ヒトや動物で起こっている疾病やそのメカニズムをとらえることができる。
2022年度は特にザンビアやガーナ、南アフリカにおいて、哺乳類(イヌ、野生げっ歯類）や爬虫類(トカゲ)のシナントロープ動物、そしてヒトの試料(尿）採集を行った。また、ヒトの食事に関する環境試料についても最終を行った。一部、ガーナより日本に試料を輸入し、解析を開始することができた。アフリカにおける農薬や重金属の環境汚染を中心に、ヒトおよびその歩哨動物となる種へのその汚染度や影響を明らかにするための解析を行っている。
日本学術振興会, 国際共同研究加速基金(国際共同研究強化(B)), 北海道大学, 22KK0163 - 外来性の化学物質（xenobiotics）に対する哺乳類の適応進化/変化
科学研究費助成事業 基盤研究(A)
2021年04月05日 - 2026年03月31日
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。
日本学術振興会, 基盤研究(A), 北海道大学, 21H04919 - 発達神経毒性の継世代影響メカニズムの解明－農薬の発生プログラム・エピゲノム毒性
科学研究費助成事業
2024年04月01日 - 2025年03月31日
星 信彦, 横山 俊史, 池中 良徳, 平野 哲史
脳の神経回路網発生プログラムにおける継世代影響発達神経毒性および継世代影響（エピゲノム毒性）を明らかにすべく，C57BL/6Nマウスを用いてクロチアニジン（CLO）とクロラントラニリプロール（CAP）を用いて検証した．その結果，無毒性量の曝露でも胎子・新生子のCLOに対する感受性が神経回路の発達ステージ（4段階）によって異なることを初めて明らかにした（doi: 10.1292/jvms.22-0570）．また，標的昆虫の骨格筋に作用点をもつCAPは，マウスでは運動機能障害を誘発せず，不安様行動の増加を引き起こすことを初めて明らかにした（doi: 10.1292/jvms.23-0041）．また，CLOの継世代影響評価では，子（F1），孫（F2），ひ孫（F3）世代の成年期で各種試験を行ったところ，母親のみが曝露されたにもかかわらず，CLOの影響はF1，F2，および直接・間接的に曝露の無いF3においても認められた（under review）．さらに，胸腺細胞の分化・成熟に寄与するとされるハッサル小体数が増加した．また，フローサイトメトリー解析から，CLOが胸腺細胞のDP細胞からCD4SP細胞への移行を阻害し，胸腺細胞の分化・成熟に影響を及ぼす可能性が示唆された．腸内細菌叢解析の結果，属レベルでは細菌組成の上位30属のうち，F1は2属，F2は1属，F3は4属が変動した．疾患やTreg細胞・マクロファージなどの誘導に関与する短鎖脂肪酸産生菌の変動（dysbiosis）はとくにF3で顕著であった．本研究により，無毒性量CLOの胎子・授乳期曝露が，一切のCLO曝露を受けていないF3世代にまでも現われることが明らかとなり，胸腺リンパ系および腸管免疫系に対する継世代影響（エピゲノム毒性）を考慮する重要性を示唆する知見が得られた（doi: 10.1292/jvms.23-0038）．
日本学術振興会, 基盤研究(B), 神戸大学, 23K25004 - 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
科学研究費助成事業 挑戦的研究(開拓)
2022年06月30日 - 2025年03月31日
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
従来型の毒性試験法では高感度な検出法が確立されておらず、その毒性を評価することが困難な疾患がその中毒症状の場合がある。本研究で提案するMulti Imaging Toxicity Assay; MITAシステムは、従来まで実験動物の安楽死を必要としていた中枢神経の活動や代謝系の観察を、マイクロCT（コンピュータ断層撮影）やPET-CT、２光子顕微鏡、イメージング質量顕微鏡などのイメージング技術を用いることにより可視化する。それにより、連続的かつ高感度で、これまで見落とされていたAdverse Effectsを検出する。
本年度は、実験ラットを用いて、マイクロCTにより、肝腫大などの外来化学物質の肝臓への影響を、安楽死前に評価する新規試験法の開発を行った。フェノバルビタールとジクロロジフェニルトリクロロエタン（DDT）をモデル化合物に、動物への曝露試験を実施した。安楽死の直後に正確な肝体積を実測し、安楽死前にCTで分析した肝体積の推定値と比較したところ、両者の間には高い正の相関がみられ、CTにより、生きたラットで肝臓サイズを評価できることを明らかにした。また、対照群と比較し、フェノバルビタールの投与群で、肝臓サイズが有意に増加する傾向をCTが検出可能であった。しかし、DDT曝露実験では同様の結果が得られず、さらなる手法の改良が望まれる。加えて、上記のラット血漿のメタボローム、リピドーム解析を実施した。セラミドなどの血中脂質が、肝臓の酸化ストレス、薬物代謝に関わる遺伝子発現量を推測するマーカー候補として抽出された。血漿脂質もCTと同様、動物の安楽死前に分析可能なパラメーターであり、両者を組み合わせることで、より高い精度で化学物質の毒性を評価可能であると期待できる。
日本学術振興会, 挑戦的研究(開拓), 北海道大学, 22K18425 - 発達神経毒性の継世代影響メカニズムの解明－農薬の発生プログラム・エピゲノム毒性
科学研究費助成事業 基盤研究(B)
2022年04月01日 - 2025年03月31日
星 信彦, 横山 俊史, 池中 良徳, 平野 哲史
日本学術振興会, 基盤研究(B), 神戸大学, 22H03750 - 犬のクッシング病の臨床的多様性を生み出す遺伝子多型とステロイドプロファイルの解析
科学研究費助成事業 基盤研究(C)
2022年04月01日 - 2025年03月31日
永田 矩之, 池中 良徳
ステロイドホルモンの過剰による様々な症状を特徴とする犬のクッシング病において、診断と治療を困難にする原因の一つである臨床像の多様性を規定する因子について解析を進めた。
ステロイドホルモン関連遺伝子の多型とステロイドプロファイルの変化が犬のクッシング病の臨床的多様性を生み出すという仮説を基に、本年度は主に健康犬のステロイドホルモンについて検討を行った。これまでの研究で確立した液体クロマトグラフィー・ トリプル四重極質量分析法（LC-MS/MS）による血中ステロイドホルモン網羅的測定法を用いて、コルチゾール、コルチゾン、コルチコステロン、プロゲステロン、17-OHプロゲステロン、デオキシコルチコステロン、11-デオキシコルチゾールを含むステロイドホルモン11種を測定した。明らかな疾患を持たない健康犬の血中の各ステロイドホルモン濃度を測定し、犬種間で比較することで、犬種によるステロイドプロファイルの多様性について検討した。3種類のステロイドホルモンにおいて犬種間で有意な差が確認され、犬種ごとにステロイドプロファイルが異なる可能性が示された。また、夾雑物が多いことにより正確な測定が困難であった尿中のステロイドホルモン分析についても、新規カラムを用いることで高感度かつ高精度な定量分析法を確立した。健康犬の尿において各ステロイドホルモンと尿中クレアチニン濃度を測定し、各ステロイドホルモン/クレアチニン比の参考基準範囲を設定した。
日本学術振興会, 基盤研究(C), 北海道大学, 22K05980 - 環境化学物質曝露による有害作用：ヒト疫学研究と動物実験による機序解明
科学研究費助成事業 基盤研究(A)
2021年04月05日 - 2025年03月31日
荒木 敦子, 小島 弘幸, 増田 秀幸, 池中 良徳, Goudarzi Houman, POUDEL KRITIKA, 中村 明枝, アイツバマイ ゆふ
疫学研究では、「北海道スタディ」に参加する9-11歳の前思春期児から収集した血漿を用いて、性ステロイドホルモン14物質の一斉分析、LH、FSH、Inhibin B、INSL3の測定を行った。曝露評価として尿中フタル酸エステル類代謝物、ノニルフェノールを測定した。フタル酸エステル類代替物質DINCH、DEHTP、DEHA代謝物分析に向けた条件検討を実施し、ピークが得られることを確認した。
曝露と健康を介在するバイオマーカーの測定に向けて、96穴プレートを用いて一度に数十種類のたんぱく質やペプチドを、20μLという非常に少量の検体を用いて分析できるBio-Plex200 multiplexアッセイシステムを購入した。機器メーカによるトレーニングに加えて、ヒトテストサンプルを用いて、Th1/Th2サイトカインにエオタキシンを加えたテストアッセイを実施し、手技や分析に問題がないことを確認し、子どもから収集した血漿を用いた測定に向けて準備を整えた。
子ども血中総IgE、好酸球、気道炎症マーカーFeNO値について、一般子ども集団のアレルギー有となしの子どもの比較により、成人のカットオフ値の妥当性について検討した。
動物・細胞実験分担研究においては、ヒト肝細胞に近い性質を示すHepaRG細胞株に0.1% DMSO（対照群）、MEHP 3 microM（低用量群）、MEHP 30 microM（高用量群）をそれぞれ24時間曝露してmRNAを採取した。GeneChip解析を用いた網羅的遺伝子発現解析を行い、核内受容体PPARalpha活性化に伴う遺伝子発現変化を認めた。さらに、妊娠ICRマウスに、0.1%DMSOを含む水（対照群）、DEHP 0.3 mg/kg（低用量群）及びDEHP 3 mg/kg（高用量群）を妊娠期間中経口曝露した。それぞれ出生後７日目の仔マウス肝臓からmRNAを採取した。
日本学術振興会, 基盤研究(A), 北海道大学, 21H04843 - 継世代影響から捉える農薬の発達神経毒性作用と神経前駆細胞・グリアの局所活動
科学研究費助成事業 挑戦的研究(萌芽)
2021年07月09日 - 2024年03月31日
星 信彦, 横山 俊史, 杉尾 翔太, 池中 良徳, 平野 哲史
C57BL/6Nマウスに妊娠1.5日目から生後3週齢までクロチアニジン（CLO）を65 mg/kg/dayの濃度（農薬評価書における無毒性量を参考）で給水ゲルを用いて自由摂取させた．対照群または投与群同士であるF1の雌雄を交配させてF2を作製し，同様にF2の雌雄を交配させてF3を作製し，各種解析を行った．その結果，投与群F1世代の3週齢において卵巣の矮小化が認められ，それはCLOのエストロゲン関連経路活性化に起因することが示唆された．投与群F1，F2世代で抗酸化酵素GPx4の陽性強度が減少した．17OHPは，F1，F3世代10週齢では減少し，F3世代3週齢では増加した．また，世代を重ねるごとに投与群で食殺および育子放棄が増加した．F1・F2世代ではオキシトシン・プロラクチンの減少に加え，F2世代ではF1世代の不十分な養育も加重されたと推測された．網羅的遺伝子解析の結果，F1・F2世代においてCyp19a1，InhβAおよびPgrの発現が増減した．F1世代の3週齢に関しては，上記3種の遺伝子発現の増加，かつ，GPx4活性が減少したことから，CLOが酸化ストレスを誘発したことが要因と考えられた．ホルモン定量解析および遺伝子発現解析において，CLOに対する反応性は3週齢と10週齢とで異なること，ならびにCLOの胎子・授乳期曝露が雌マウスにおいて継世代影響を及ぼすことが明らかになった．また．本研究の知見に基づき，CLOのAOPを初めて明らかにした（doi: 10.1292/jvms.21-0014）．「①神経行動学的影響」及び「②二光子顕微鏡を用いた生体蛍光イメージング」については以下を参照のこと．
①doi: 10.1292/jvms.20-0721，②doi: 10.1292/jvms.22-0013，doi: 10.1038/s41598-022-09038-7
日本学術振興会, 挑戦的研究(萌芽), 神戸大学, 21K19846 - 魚類を指標としたイオン性環境汚染物質による脳移行の実態とリスク評価法の開発
科学研究費助成事業 基盤研究(A)
2020年04月01日 - 2024年03月31日
野見山 桂, 岩田 久人, 池中 良徳, 久保田 彰, 田上 瑠美, 江口 哲史
魚類への下水処理水in vivo曝露試験を実施し、PPCPs 78種を対象に特異な移行・残留性を示す物質の探索を実施した。浮上した化学物質に対して、取込速度定数、排泄速度定数、消失半減期、体内分布、血しょうたんぱく結合率、肝S9代謝速度定数などのADMEパラメータから要因の特定を試みた。生物濃縮係数の実測値と化学物質の脂溶性に基づき予測される予測生物濃縮係数を比較したところ、約60%以上の物質において実測値は誤差1桁以内の精度で予測可能であることが示された。一方、残余約40%については、実測値が測生物濃縮係数に比べ1－2桁高値を示す物質（Haloperidol、Chlorpheniramine、Gemfibrozil）と実測値が予測生物濃縮係数に比べ2－4桁低値を示す物質（Telmisartan、Fexofenadine、Rebamipide、Triclocarbanなど）が存在した。これらの要因として、前者の場合では、取込速度定数が比較的高値を示し、血しょうたんぱく結合率も比較的高値であったことから、脂質以外への分配（たんぱく結合など）、後者の場合では、排泄速度定数が比較的高値（消失半減期は1.6－20h）を示したことから、速やかな代謝・排泄が推察された。ティラピア血しょうにおいて実測値>>予測生物濃縮係数を示したHaloperidolとChlorpheniramineの実測値は、それぞれコイの60倍、150倍高値を示した。Chlorpheniramineの血しょうたんぱく結合率は、ティラピアで95－98%、コイで61－74%であり、たんぱく非結合型の割合に約10倍の差が認められたことから、Chlorpheniramineはティラピアの血中のたんぱく質に特異的に結合することにより、血中に高濃縮・高残留するものと推察された。
日本学術振興会, 基盤研究(A), 愛媛大学, 20H00645 - 副腎－肝臓連関によるイヌ肝細胞癌発症メカニズムの解明
科学研究費助成事業 基盤研究(B)
2020年04月01日 - 2023年03月31日
滝口 満喜, 村上 正晃, 山崎 淳平, 池中 良徳
我々の過去の研究により、ステロイドホルモン産生過剰を病態とする副腎皮質機能亢進症は犬の肝細胞癌の発症リスクとなりうることが示された。そこで犬肝細胞癌の多段階発癌メカニズム、①ステロイドホルモン過剰による肝細胞障害、②長期的なステロイド曝露による肝細胞内での炎症蓄積、そして③エピゲノム変異による癌化、を提唱するに至った。
本研究の初年度である本年は、多段階発癌メカニズムの出発点となるステロイドホルモン過剰の病態を明らかにすることを目指し、液体クロマトグラフィタンデム質量分析計（LC-MS/MS）による副腎皮質ホルモンの網羅的測定を行った。肝細胞癌症例13例、副腎皮質機能亢進症症例17例、併発症例12例、非副腎疾患症例9例の4群において副腎皮質で産生される主要ホルモン9種類の測定を行った。しかし、測定対象とした副腎で産生される9種類のホルモンには、疾患特異的なパターンもしくは疾患群間が認められなかった。ステロイドホルモンの網羅的解析と並行して肝臓癌組織のエピゲノム変異解析も行った。まずは正常肝臓5検体、実験的ステロイドホルモン誘発性脂肪肝5検体、肝細胞癌12検体を対象にDNAメチル化解析を行った。その結果、正常肝臓および実験的ステロイドホルモン誘発性脂肪肝の間にはエピゲノム変異は認められなかった。一方で肝細胞癌のDNAメチル化パターンは正常肝臓および実験的ステロイドホルモン誘発性脂肪肝と異なることが確認された。
本年度の研究では副腎皮質ホルモンの網羅的測定が安定的に実施できるようになり、より多くのステロイドホルモンや代謝産物へと測定対象を広げていくことが可能となった。また、肝細胞癌に疾患特異的なエピゲノム変異のあることが確認され、今後の肝細胞癌の発癌メカニズム研究に貢献できる。
日本学術振興会, 基盤研究(B), 北海道大学, 20H03139 - 殺虫剤の「生物学的モニタリングに基づく適応的リスク評価法」の開発と実践
科学研究費助成事業 基盤研究(B)
2019年04月01日 - 2022年03月31日
星 信彦, 横山 俊史, 池中 良徳, 平野 哲史, 市川 剛
BM-ARAの基礎データ取得のため，高次脳機能への影響をin vivoレベルで解析した．
個体レベルでの評価：各種殺虫剤曝露により，自発運動量／不安様行動，ストレス抵抗性，学習／短期記憶，社会性・恐怖心等に関する行動試験実施し，ストレス関連行動を同時に測定した．新奇環境下で特有のヒト可聴域の異常啼鳴が認められ，雌では発情期のみで観察された．加齢影響実験では，老年群で代謝能の加齢変化に起因して成年群とは異なる行動影響が初めて明らかとなった．フィプロニルやジノテフランでは自発運動能が増加し，多動の惹起が観察された．上記行動変化には明らかな雌雄差が認められ，その影響は雄動物で顕著であった．クロチアニジン(CLO)の亜慢性曝露で，胸腺重量は30%減少し，胸腺・脾臓・リンパ節におけるマクロファージ数が有意に低下した．腸内細菌叢解析により，CLOにより酪酸産生菌が顕著に減少し，腸内細菌叢の多様性の低下傾向も認められた．妊娠動物を用い，胎子への移行量を含むADME（吸収・分布・代謝・排泄）を求め，基本的なToxicokinetics / Dynamicsを明らかにした．
組織レベルでの評価：海馬歯状回，手綱核のc-fos陽性細胞数は雄のみで有意に増加した．視床下部弓状核におけるERα発現量の変化が認められた．CLOの亜慢性投与による覚醒下マウスの脳内神経細胞およびミクログリアの動的変化について二光子顕微鏡を用いて検証した結果，神経細胞の興奮性の質の変化が認められた．
細胞・分子レベルでの評価：視床下部弓状核におけるERα発現量の変化が認められた．胎子期曝露により，生殖細胞，上皮組織，卵胞，ホルモンの機能上昇，エストロゲン依存性乳癌，エストロゲン生合成，GnRHパスウェイの活性化が明らかとなった．
以上は，いずれも農薬評価書における無毒性量以下での結果であることを明記する．
日本学術振興会, 基盤研究(B), 神戸大学, 19H04277 - 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
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))
2018年10月09日 - 2022年03月31日
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。2018年度は、これらの国との共同研究を実施し、ザンビアにおいて鉛汚染、南アフリカではDDT、ガーナではネオニコチノイドなどに関する共同研究を推進した。このうち、ザンビアおよび南アフリカは現地に渡航し、また南アフリカの研究者を日本に招聘した。ガーナに関しては共同研究に関するMOUの作成およびガーナの倫理機関において申請手続きを行い、試料採集を実施した。
日本学術振興会, 国際共同研究加速基金(国際共同研究強化(B)), 北海道大学, 18KK0287 - 有機フッ素化合物の第二次性徴への影響解明ー出生コホートと細胞アッセイ系による研究
科学研究費助成事業 基盤研究(B)
2018年04月01日 - 2022年03月31日
荒木 敦子, 小島 弘幸, 小林 澄貴, 守屋 仁彦, 池中 良徳, 宮下 ちひろ, 岸 玲子, アイツバマイ ゆふ
北海道スタディに参加者504名の母体血清中のPFOS/PFOA濃度と臍帯血中の性ホルモン濃度、臍帯血中DNAのCYP17A1、CYP19A1、HSD3B1、HSD3B2、HSD17B1、HSD17B3遺伝子にある12か所の一塩基多型(SNPs)を解析した。PFOS濃度とHSD17B1（rs676387およびrs2675531）遺伝型との交互作用がDHEA/A-dione濃度と関連を示した。HSD17B1遺伝型で層別解析したところ、HSD17B1(rs676387)-GG/GA型ではPFOS濃度が2倍増えるとDHEA/A-dioneは0.115（95%CI: -0.294, 0.065）減少したのに対し、AA型では0.476（-0.276, 0.979）増加した。HSD17B1(rs2676531)-CC/CT型ではPFOS濃度が2倍増えるとDHEA/A-dioneは0.138（95%CI: -0.335, 0.060）減少したのに対し、TT型では0.535（0.013, 1.057）増加した。児のHSD17B1遺伝型は、母体血清PFOS濃度と児の性ホルモン濃度との関連に違いを及ぼす可能性が示唆された。
in vitro細胞アッセイ系を用いてPFAS11化合物のpregnane X receptor(PXR)、constitutive androstane receptor(CAR)、peroxisome proliferators-activated receptor(PPAR)α、PPARβ、PPARγの各種ヒト核内受容体に対するアゴニスト活性を調べた。PFOA及びPFNAが高用量でPPARalpha;アゴニスト活性を示したが、PXR・CAR・PPARalpha,PPARganmaに対するアゴニスト活性は認められなかった。また、PFASsの遺伝子発現に及ぼす影響評価として、ヒト血中濃度の高いPFOA及びPFNAをそれぞれヒト肝細胞株に曝露してmRNAを採取した。
日本学術振興会, 基盤研究(B), 北海道大学, 18H03035 - 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
科学研究費助成事業 基盤研究(A)
2018年04月01日 - 2022年03月31日
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, 加藤 恵介, 宮原 裕一, 市川 剛, 岡松 優子, 中山 翔太, 平野 哲史
本年度は研究実施計画通り、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。特にゼブラフィッシュは行動試験を実施するための基盤設備を整備した。また、同時に各系統について胎児への移行量を含む、ADME（吸収・分布・代謝・排泄）を求め、基本的なToxico Kinetics/Dynamics を明らかにした。
・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、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が、未だ検出に至っていない。対象化学物質の検出のための、各種条件検討が必要である。
・細胞・分子レベルでの評価：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：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。その結果、日本人は新生児から曝露を受けている事、その摂取源は飲食物である事が明らかになった。
日本学術振興会, 基盤研究(A), 北海道大学, 18H04132 - イオン性環境汚染物質がもたらす神経伝達物質への影響の理解と評価法の開発
科学研究費助成事業 挑戦的研究(萌芽)
2019年06月28日 - 2021年03月31日
野見山 桂, 水川 葉月, 池中 良徳
脳組織中のモノアミン類・アミノ酸類等の多様な神経伝達物質および代謝産物数十種（目標40種）を標的とし、脳移行に伴う神経伝達物質の変化を包括的に分析できる手法を開発する。高マトリクスな脳試料を対象とするため、メタボロミクス分析の前処理で使用しているジルコニアカラムを用いたリン脂質の除去と固相抽出、および限外ろ過フィルターを使ったタンパク除去等の前処理法を検討し、それらを組み合わせて、高精度なクリーンアップ法を確立する。さらに、定量性・感度に優れたLC-MS/MS (AB SCIEX QTRAP5500)の使用により高感度・高選択性を達成し、ハイスループットかつ定量性を機能化した方法を開発をめざした。
イヌ・ネコ・ラット・鯉の脳組織を対象に抽出溶媒と内部標準物質を添加し、超音波抽出後、遠心分離(15,000×g, 20 min, 4℃)した。得られた上澄みを採取し、アセトニトリル添加によりタンパクを沈殿・除去した後、対象物質をLC (Shimadzu, UFLC XR)-MS/MS (AB Sciex, Qtrap 5500）で定性・定量した。対象物質はDopamineとNorepinephrineを含むチロシン代謝系、Serotoninを含むトリプトファン代謝系およびヒスチジン代謝系に分類される活性体とその前駆体や代謝物の計13種を選定し、本分析法の補正回収率は71-100%、日内変動は<7%、日間変動は<10%と良好な確度・精度を示した。
日本学術振興会, 挑戦的研究(萌芽), 愛媛大学, 19K22933 - 「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
科学研究費助成事業 挑戦的研究(萌芽)
2018年06月29日 - 2020年03月31日
石塚 真由美, 池中 良徳, 中山 翔太
野生齧歯類は35種以上の人獣共通感染症を媒介する。また、野生ラットは繁殖力の強さから離島へ生息域を広げ外来動物として 生態系を攪乱している。齧歯類の駆除方策として、殺鼠剤ワルファリンなど抗凝血系化学物質が比較的安全性が高いため広く利用された。一方、度重なる使用により抵抗性を持つ個体群が世界各地に出現している。その対策に欧米では致死性の高い第二世 代抗凝血系殺鼠剤が用いられている。しかしながら、これらは毒性が強く駆除対象外生物の二次被害が絶えない。一方、選択性の高い新規殺鼠剤の開発は、感受性種差に関する毒性学的知見も服なく、困難である。当該研究は、in silicoシミュレーショ ンによるサンプル入手が困難な抵抗性ラット・鳥類種における殺鼠剤感受性評価法の確立を目的とする。
今年度は、ビタミンKエポキシド還元酵素（VKOR）やシトクロムP450（CYPs）について研究を進めた。殺鼠剤の標的生物であるラットにおける抵抗性メカニズムについて、分析を行った。電子伝達系に関して抵抗性個体ではこの機構が明らかに高活性であることを明らかにし、これが抵抗性獲得の一因であることが予測された。この研究を進める際に、ビタミンKエポキシド還元酵素活性の新たな分析方法も構築して実験を進めた。殺鼠剤を投与し、血中濃度や血液凝固時間を測定したところ、対象動物であるラットなど齧歯類に比して、比較的感受性が低いことが分かった。
上記の試験系により同定した抵抗性獲得因子をターゲットとする新規殺鼠剤を作成することを目的として、シトクロムP450阻害剤と殺鼠剤との併用によるin vivo試験を実施した。海産物から得られた天然素材を用いた試験では想定した効果は得られなかったが、CYPの典型的な阻害剤を併用投与したラットでは血中の殺鼠剤濃度が上昇し、一定の効果が出ることがわかった。
日本学術振興会, 挑戦的研究(萌芽), 北海道大学, 18K19847 - 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
科学研究費助成事業 基盤研究(A)
2016年04月01日 - 2020年03月31日
石塚 真由美, 池中 良徳, 中山 翔太, 水川 葉月
動物はヒトと同じく多くの環境化学物質に曝露されており、環境化学物質による集団死は野生動物では世界的にも恒常的に起こっている。また、日常的な化学物 質曝露は野生動物に病態を引き起こしていることがこれまでの 研究により明らかになりつつある。一方で、動物の化学物質の感受性の種差や個体差に関する研究 は少なく、化学物質のリスク管理を難しくし、また、野生動物のケミカルハザード(化学物質の有害性による被害)を引き起こ す原因となっている。本研究では 野生動物、とくに生態系で高次に立つ野生哺乳類と野生鳥類の化学物質感受性 に関して種差や個体差を引き起こしているその要因を明らかにし、データベースの 構築を行うと同時に、環境適 応への分子進化過程を高等動物で初めて明らかにすることを目的とした。 平成29年度では、下記の研究を進め、成果を得た。
１）哺乳類について、UGT1ファミリーおよびUGT2ファミリーの動物種差について明らかにした。特に食肉目の動物に関して、UGTの特徴を明らかにすることができた。また、同時に、雑食性動物や草食動物などに関して、ゲノム上でのUGTの特徴について、in silico解析から明らかにすることができた。
２）鳥類について、UGTファミリーの分布とそのゲノム構造について明らかにした。
３）哺乳類、鳥類について食性とUGT活性との関係性について明らかにした。
４）殺鼠剤をモデル化合物として、その感受性に関する新規のメカニズムを提唱した。
日本学術振興会, 基盤研究(A), 北海道大学, 16H01779 - 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
科学研究費助成事業 挑戦的研究(萌芽)
2017年06月30日 - 2019年03月31日
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
化学物質の感受性の差は種により数千倍に及ぶこともあり、実験動物を用いた毒性試験の結果を野生動物にそのまま外挿することは難しい。特に希少トッププレデターでは、化学物質の影響を直接観察できるin vivo実験は実質困難であり、それゆえ化学物質感受性の“種差”を適切に評価できる実験系は未だ存在していない。そこで、本研究では、化学物質感受性決定因子である薬物代謝“Metabolism”を、野生動物の皮膚線維芽細胞より作成した誘導性肝臓様細胞(iHep)を用いて評価することを試みた。
2018年度は2017年度に引き続き、①野生動物の皮膚線維芽細胞の培養およびiHep細胞への誘導因子の選定および、②肉食動物の薬物代謝第II相抱合酵素活性、特に硫酸抱合酵素（SULT）の評価を実施した。
先ず、①の実験では、野生動物の線維芽細胞として、エゾヒグマおよびツシマヤマネコの保存に成功し、その後のiHep誘導実験に供試した。ただ、いくつかの誘導因子を導入し、誘導を試みたが、成功には至らなかった。
②の実験では、野生動物の中で、鰭足類動物において、エストロゲン代謝に重要な分子種であるSULT1E1が遺伝的に欠損している事を明らかにし、多くの化学物質に対して高感受性を示す可能性を示唆する知見が得られた。
日本学術振興会, 挑戦的研究(萌芽), 北海道大学, 17K20038 - 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
科学研究費助成事業 基盤研究(C)
2015年04月01日 - 2019年03月31日
平 久美子, 池中 良徳, 中山 翔太
ヒトのネオニコチノイド（NN）曝露指標となりうる尿中代謝物を同定し分析法を確立しフィールドレベルでの検出を確認した。またNNがヒト血漿中で代謝されないことを確認した。
①主要代謝物の同定：ウサギにNN７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った。イミダクロプリドで水酸化物IMI-5OHなど5種、アセタミプリドで脱メチルアセタミプリド1種、ニテンピラムで脱メチル体など6種、チアクロプリドでTHI-4OHやそのグルクロン酸抱合体など7種が検出、クロチアニジンで脱メチル体、チアメトキサムから、クロチアニジン他2種、ジノテフランから脱メチル体など5種が検出された。
②代謝物の生体試料分析法の確立：主要代謝物の構造解析とその有機合成を行い、LC-ESI/MS/MSを用いた高感度分析法を開発し、親化合物7種、内部標準物質7種に加え代謝産物21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において可能となった。
③様々な集団での尿中NNおよび代謝物分析：②を用いフィールドレベルで随時尿を収集し分析した。日本で3-6歳の幼児46人の尿を分析し、90%で同時に2種以上のNNまたは脱メチルアセタミプリドを検出した。スリランカの住民96人の尿を分析し、イミダクロプリド、クロチアニジン、チアメトキサム、脱メチルアセタミプリド、脱メチルニテンピラム、5-OHイミダクロプリド、4OHイミダクロプリドを検出した。また近年急激にNNの使用量が増加しているガーナの成人300人の尿を分析し、NN5種と脱メチルアセタミプリドを検出した。
④血漿画分を用いた代謝試験: NNは細胞内Cytochrome P450により代謝を受けることが報告されている。本試験で血漿酵素による代謝は認められなかった。
日本学術振興会, 基盤研究(C), 東京女子医科大学, 15K00559 - 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
科学研究費助成事業 挑戦的萌芽研究
2016年04月01日 - 2018年03月31日
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。
日本学術振興会, 挑戦的萌芽研究, 北海道大学, 16K15034 - 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
科学研究費助成事業 若手研究(B)
2016年04月01日 - 2018年03月31日
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。
日本学術振興会, 若手研究(B), 北海道大学, 16K16197 - スリランカにおける慢性腎臓病の原因調査と飲料水中からのフッ素除去
科学研究費助成事業 基盤研究(B)
2015年04月01日 - 2018年03月31日
川上 智規, 平 久美子, 池中 良徳, 袋布 昌幹
カドミウム、鉛、クロム、ヒ素はCKDuの原因物質ではないと明確に結論付けることができた。CKDu患者の症状はネオニコチノイド中毒による症状と矛盾しなかったが、ネオニコチノイドがCKDuに関わっていると判断するには至らなかった。アヌラダプラに炭素電極電解法によるフッ素除去装置を設置した。フッ素濃度を2.1 mg/Lから0.4 mg/L程度にまで低下させることができ、スリランカの飲料水基準である1 mg/Lを下回る水質を得ることができた。炭素電極電解法の後段に鳥骨炭フィルターを設置したハイブリッド方式のフッ素除去装置を２カ所設置し、フッ素濃度を0 mg/Lにまで下げることができた。
日本学術振興会, 基盤研究(B), 富山県立大学, 15H05120 - 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
科学研究費助成事業 若手研究(B)
2015年04月01日 - 2018年03月31日
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。
日本学術振興会, 若手研究(B), 北海道大学, 15K16132 - 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
科学研究費助成事業 基盤研究(B)
2015年04月01日 - 2018年03月31日
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。
日本学術振興会, 基盤研究(B), 北海道大学, 研究代表者, 競争的資金, 15H02825 - 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
科学研究費助成事業 挑戦的萌芽研究
2015年04月01日 - 2017年03月31日
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。
日本学術振興会, 挑戦的萌芽研究, 北海道大学, 研究代表者, 競争的資金, 15K12213 - 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
科学研究費助成事業 基盤研究(B)
2014年04月01日 - 2017年03月31日
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。
日本学術振興会, 基盤研究(B), 北海道大学, 研究代表者, 競争的資金, 26304043 - 化学物質汚染に対する産業動物の生体防御機構の研究基盤
科学研究費助成事業 基盤研究(A)
2012年04月01日 - 2016年03月31日
石塚 真由美, 池中 良徳, 坪田 敏男, 今内 覚
産業動物について、第I相反応であるシトクロムP450、第II相反応であるグルクロン酸抱合および硫酸抱合酵素について種差を明らかにした。哺乳類の尿におけるグルクロン酸抱合と硫酸抱合体比を比較し、その特徴を明らかにした。また、国内外の産業動物に蓄積する環境化学物質を分析し、ウシなどについては、重金属蓄積性が比較的高いことを見出した。鳥類について家禽を中心にトランスクリプトーム解析を行い、肝臓に発現する第I相反応酵素および第II相反応酵素の網羅的解析を行った。以上の研究により、産業動物の化学物質に対する防御機構を、異物代謝酵素を中心に明らかにした。
日本学術振興会, 基盤研究(A), 北海道大学, 連携研究者, 競争的資金, 24248056 - 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
科学研究費助成事業 研究活動スタート支援
2013年08月30日 - 2015年03月31日
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。
日本学術振興会, 研究活動スタート支援, 北海道大学, 25892001 - アフリカ諸国の食の化学物質汚染のサーベイランスとモニタリング法の開発
科学研究費助成事業 基盤研究(B)
2012年04月01日 - 2015年03月31日
石塚 真由美, 池中 良徳
アフリカはすでに、急激な開発による「副作用」を受け、化学物質の汚染は生態系の浄化作用では対処できない地域が顕在化している。我々の予備調査では、食肉や魚類の有害金属やDDTの濃度はWHO基準を超えており、アフリカ諸国の食の化学物質汚染の現状の把握は喫緊の問題となっている。本研究では、ザンビア、南アフリカ、ガーナ、エジプト、エチオピアにおける家畜を中心とした環境汚染の影響を明らかにし、環境汚染が食の安全やヒトの健康に及ぼすリスクについて報告した。
日本学術振興会, 基盤研究(B), 北海道大学, 連携研究者, 競争的資金, 24405004 - アフリカにおける環境毒性研究と異物代謝系の種差に注目したリスク評価
科学研究費助成事業 若手研究(B)
2011年 - 2012年
池中 良徳
当該研究では希少な生態系が成り立つアフリカを中心に、野生動物と環境試料の採集を行い、環境毒性研究を展開した。まず、野生動物に対する異物代謝系の種差を主に第II相抱合反応に注目し明らかにした。11種の哺乳類の尿を用いたスクリーニングでは、現在まで硫酸抱合活性が低いと考えられてきたブタで硫酸抱合化Pyreneが検出された。また、カイネティックス解析の結果、ブタの酵素効率はラットよりも高いことが明らかになった。一方、アフリカで行った調査では、両生類、哺乳類、鳥類の尿及び臓器を採取した。これらの試料について、重金属類や農薬類を中心に化学分析を行った結果、一部の地域からきわめて高濃度の化学物質が検出され、特に鳥類において他の生物種に比べ高い濃度で化学物質を蓄積している傾向が観察された。
日本学術振興会, 若手研究(B), 北海道大学, 研究代表者, 競争的資金, 23710038 - 環境化学物質が引き起こす野生動物への免疫抑制と集団感染症へのリスク評価
科学研究費助成事業 研究活動スタート支援
2009年 - 2010年
池中 良徳
当該研究では、「化学物質を起因とする野生動物の病態」の中で、特に「免疫抑制」に焦点をあて、その現状をフィールドレベルで調査・研究を行った。調査地域であるザンビア共和国では、鉱業活動の影響により、家畜であるウシやげっ歯類において、炎症性サイトカインや酸化ストレスマーカーの変動が明らかになり、重金属への曝露が免疫応答に影響を与えている可能性が示唆された。これら得られた免疫かく乱の結果と土壌中重金属濃度のGISの結果を併せて解析した結果、土壌の汚染分布と生物中蓄積濃度やMT発現量との間に相関は見られず、摂餌などのその他の要因の影響が強いことが示唆された。
日本学術振興会, 研究活動スタート支援, 北海道大学, 研究代表者, 競争的資金, 21810001 - 環境汚染と希少野生プレデターにおける化学発癌
科学研究費助成事業 基盤研究(A)
2007年 - 2010年
藤田 正一, 池中 良徳, 石塚 真由美, 坂本 健太郎, 石塚 真由美, 坂本 健太郎
当該研究では、希少動物を含む生態系高次の動物について発がん物質の影響を調べるために、癌原物質を代謝的に活性化するシトクロムP450(CYP)1A1、及びその転写調節因子アリルハイドロカーボン受容体、活性代謝中間体を抱合する抱合酵素の種差を中心に調べ、その基質との親和性や分子進化について明らかにした。また、野生動物における発がん物質など環境汚染物質の蓄積とその影響について、野生げっ歯類を中心とした歩哨動物を用いて分析した。
日本学術振興会, 基盤研究(A), 北海道大学, 連携研究者, 競争的資金, 19208028 - 甲殻類が持つ生体外異物に対する受容・応答の分子基盤と新規代謝機構の解明
科学研究費助成事業 特別研究員奨励費
2007年 - 2008年
池中 良徳
化学物質の代謝能は,各生物種により非常に多様である。その結果,生物種間で化学物質の蓄積特性に違いが生じ,その化学物質耐性にまで影響がおよぶ。一方,化学物質の生態系への影響は未だ不明な点が多い。その原因の一つとして,化学物質の毒性メカニズムや代謝メカニズムの研究が主に魚類や哺乳類など,脊椎動物を対象としたものであり,地球上に生息する動物のうち95%を占めると言われている無脊椎動物についてほとんど注目されてこなかったことが挙げられる。そこで本研究では,無脊椎動物の中でも,水圏において特にバイオマスの大きい甲殻類に注目し,その異物代謝第一相反応の主要な酵素群であるシトクロムP450と異物代謝第二相反応のcharacterizationを行った。その結果,甲殻類は,脊椎動物や昆虫類を含む他の無脊椎動物とは異なる独自の異物代謝反応を行っていることが明らかになった。
これまで,脊椎動物や昆虫類などの無脊椎動物で生成される抱合体は,グルコース抱合体,グルクロン酸抱合体,および硫酸抱合体であることが報告されてきた。しかし,甲殻類ではこれら抱合体の他に,グルコースに対し更に硫酸が負荷した「グルコース-硫酸抱合体」を生成していた。一方、本研究によりフィールドレベルで行った調査により、魚類と甲殻類では明らかに多環芳香族炭化水素類(PAHs)の蓄積特性が異なった。本研究で明らかにした甲殻類の特徴的な代謝反応が、フィールドで実際に観察された化学物質の蓄積特性に影響を与えたと考えられる。
本研究により、化学物質の蓄積特性・感受性の種差に対する、異物代謝系の新たなメカニズムを解明できた。
日本学術振興会, 特別研究員奨励費, 07J10117
