Researcher basic information

• PhD (Science), Shinshu University, Mar. 2008

• https://researchmap.jp/y_ike?lang=en

• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201201034702544985
• http://kaken.nii.ac.jp/d/r/40543509.ja.html

• 201201034702544985

• LC/MS
• 環境汚染
• シトクロムP450
• 野生動物
• アフリカ
• アフリカ地域
• 免疫抑制
• サイトカイン
• 感染症
• Pyrene
• 化学物質感受性
• 免疫かく乱
• 環境化学物質
• 重金属
• 第II相抱合反応
• 飼育動物
• 環境汚染バイオマーカー
• アフリカ諸国
• メタロチオネイン
• インターロイキン
• 異物代謝系
• 種差
• 生態系影響評価
• 産業動物
• グルクロン酸転移酵素
• 獣医学
• プレデター
• 化学発癌
• 硫酸転移酵素
• グルタチオン転移酵素
• センシング
• GIS

• Environmental Science/Agriculture Science, Chemical substance influence on environment
• Environmental Science/Agriculture Science, Radiation influence
• Environmental Science/Agriculture Science, Environmental policy and social systems
• Environmental Science/Agriculture Science, Environmental impact assessment
• Environmental Science/Agriculture Science, Landscape science
• Environmental Science/Agriculture Science, Environmental agriculture

• Bachelor's degree program, School of Veterinary Medicine
• Doctoral (PhD) degree program, Graduate School of Veterinary Medicine

Research activity information

• Jun. 2021, The Japanese Society of Veterinary Science, Veterinary Science Awards
  Elucidation of species differences in the accumulation, metabolism and sensitivity differences of the chemical substances and evaluation of their toxic effects
  Yoshinori Ikenaka
• 2020, 日本食品化学会, 島津製作所論文賞

• Micro- and mesoplastic contaminants in marine diving ducks: A first assessments from the coast of Japan
  Yurika Tokunaga; Naoko Yoshizato; Hideshige Takada; Kosuke Tanaka; Kazuhiko Hirata; Sachiko Moriguchi; Takuya Kato; Yoshinori Ikenaka; Shouta M. M. Nakayama; Shin-ichi Hayama; Mayumi Ishizuka
  MARINE POLLUTION BULLETIN, 226, May 2026
  English, Scientific journal
• 'Widespread PFAS contamination in pet food: Dietary sources and health risks to companion animals' [Environ. Pollut. 395, 15 April 2026, 127779]
  Kei Nomiyama; Aika Sato; Rumi Tanoue; Kohei Saeki; Yoshinori Ikenaka; Hazuki Mizukawa
  ENVIRONMENTAL POLLUTION, 396, 01 May 2026
  English
• Occurrence and Risk of Systemic Insecticides and Metabolites in Source and Tap Water of High-Rice-Producing Regions in Japan
  Zanne Sandriati Putri; Toshiko Sato; Tadashi Kondoh; Yoshinori Ikenaka; Masumi Yamamuro
  ACS ES&T WATER, 6, 4, 2319, 2330, 10 Apr. 2026
  English, Scientific journal
• Potential human exposure to systemic insecticides via alcoholic beverages: first report on Japanese sakes
  Zanne Sandriati Putri; Tadashi Kondoh; Yoshinori Ikenaka; Masumi Yamamuro
  FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT, 43, 4, 561, 574, 03 Apr. 2026
  English, Scientific journal
• Intergenerational sex-specific transcriptomic alterations in gonads of mice after parental lead exposure (vol 140, 109154, 2026)
  Nelly Banda; Kanami Watanabe; John Yabe; Rio Doya; Kaampwe Muzandu; Yared Beyene Yohannes; Andrew Kataba; Yoshinori Ikenaka; Mayumi Ishizuka; Shouta M. M. Nakayama
  REPRODUCTIVE TOXICOLOGY, 141, Apr. 2026
  English
• Reductive dominance and limited cytochrome P450 activity in neonicotinoid metabolism by elephant liver microsomes
  Kanami Watanabe; Kraisiri Khidkhan; Aksorn Saengtienchai; Chaleamchat Somgrid; Patcharapa Towiboon; Taweepoke Angkawanish; Warangkhana Langkaphin; Kittikul Namwongprom; Narueporn Kittisirik; Yared B. Yohannes; Yoshinori Ikenaka; Shouta M. M. Nakayama; Mayumi Ishizuka
  JOURNAL OF VETERINARY MEDICAL SCIENCE, 88, 4, 607, 613, Apr. 2026
  English, Scientific journal
• Widespread PFAS contamination in pet food: Dietary sources and health risks to companion animals
  Kei Nomiyama; Aika Sato; Rumi Tanoue; Kohei Saeki; Yoshinori Ikenaka; Hazuki Mizukawa
  Environmental Pollution, 395, 127779, 127779, Apr. 2026
  English, Scientific journal
• Assessment of a baloxavir marboxil treatment protocol for high pathogenicity avian influenza in Okinawa Rails, an endangered species endemic to Japan
  Mariko Miki; Yo Shimazu; Ryo Daniel Obara; Takashi Nagamine; Yumiko Nakaya; Yoshinori Ikenaka; Hiromi Osaki; Takashi Kimura; Takahiro Hiono; Norikazu Isoda; Takao Shishido; Yoshihiro Sakoda
  PLOS ONE, 21, 3, 23 Mar. 2026
  English, Scientific journal
• Intergenerational sex-specific transcriptomic alterations in gonads of mice after parental lead exposure
  Nelly Banda; Kanami Watanabe; John Yabe; Rio Doya; Yared Beyene Yohannes; Yoshinori Ikenaka; Mayumi Ishizuka; Shouta M. M. Nakayama
  REPRODUCTIVE TOXICOLOGY, 140, Mar. 2026
  English, Scientific journal
• Paternal Exposure to the Neonicotinoid Pesticide Clothianidin Alters Sperm MicroRNA Profiles in Mice and Intergenerationally Reduces Locomotor Activity in Male Offspring
  Makiko Ito; Tetsushi Hirano; Sarika Nunobiki; Ayano Yoshimoto; Yukako Hara; Yuya Ishida; Sakura Yonoichi; Youhei Mantani; Toshifumi Yokoyama; Yoshiaki Tabuchi; Yoshinori Ikenaka; Nobuhiko Hoshi
  JOURNAL OF APPLIED TOXICOLOGY, 17 Feb. 2026
  English, Scientific journal
• 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, Dec. 2025, [International Magazine]
  English, Scientific journal
• Technical note: Quantitative and qualitative analysis of diatom testing in methomyl poisoning case.
  Yuko Kihara; Shigeki Tsuneya; Makoto Nakajima; Suguru Torimitsu; Fumiko Chiba; Aki Tanaka; Hiroyuki Tanaka; Keigo Osada; Kanju Saka; Kanako Noritake; Mayumi Ishizuka; Yoshinori Ikenaka; Hirotaro Iwase; Yohsuke Makino
  International journal of legal medicine, 140, 2, 837, 843, 21 Nov. 2025, [International Magazine]
  English, Scientific journal
• Significant reduction of blood and tissue lead and cadmium concentrations in free-range and broiler chickens through soil remediation with biochar, phosphates, and calcined dolomite: Implications for public health and food safety
  Madalitso Tembo; Andrew Kataba; Nyein Chan Soe; Rio Doya; Richard Musonda; Golden Zyambo; Yoshinori Ikenaka; John Yabe; Kaampwe Muzandu; Mayumi Ishizuka; Shouta M. M. Nakayama
  JOURNAL OF HAZARDOUS MATERIALS ADVANCES, 20, Nov. 2025
  English, Scientific journal
• Development of a silica gel chromatography-based cleanup method for quantification of polystyrene nanoplastics in tissue samples via pyrolysis-GC/MS
  Yurika Tokunaga; Kosuke Tanaka; Go Suzuki; Nami Shimizu; Yoshinori Ikenaka; Shouta M. M. Nakayama; Mayumi Ishizuka
  JOURNAL OF HAZARDOUS MATERIALS LETTERS, 6, Nov. 2025
  English, Scientific journal
• 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, 87, 12, 1494, 1498, 29 Oct. 2025, [Domestic magazines]
  English, Scientific journal
• Risk assessment of polycyclic aromatic hydrocarbons in airborne particulates of Ulaanbaatar City, Mongolia
  Javzandolgor Tserendorj; Jajinjav Yondonjamts; Bolortuya Damdinsuren; Shagjjamba Dagva; Bayanjargal Unenbat; Sukhbaatar Batchuluun; Yared Beyene; Shouta M. M. Nakayama; Mayumi Ishizuka; Chinzorig Radnaabazar; Yoshinori Ikenaka; Munkhbat Byambajav
  AIR QUALITY ATMOSPHERE AND HEALTH, 18, 11, 3613, 3627, 28 Oct. 2025
  English, Scientific journal
• Exploring the intricacies of indoor dust pollution from neonicotinoid insecticides and its human health impacts: An exemplar from eleven agricultural communities in Ghana, West Africa.
  Collins Nimako; Osei Akoto; Nathaniel Boadi; Prince Ofori; Yared B Yohannes; Shouta M M Nakayama; Yoshinori Ikenaka; Mayumi Ishizuka
  Journal of hazardous materials, 500, 140172, 140172, 26 Oct. 2025, [International Magazine]
  English, Scientific journal
• 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, 08 Sep. 2025, [International Magazine]
  English, Scientific journal
• 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, 09 Aug. 2025, [International Magazine]
  English, Scientific journal
• 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, Aug. 2025, [International Magazine]
  English, Scientific journal
• Human plasma protein bindings of neonicotinoid insecticides and metabolites.
  Kumiko Taira; Yoshinori Ikenaka; Jean-Marc Bonmatin; Anton Safer
  Scientific reports, 15, 1, 13155, 13155, 16 Apr. 2025, [International Magazine]
  English, Scientific journal
• 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, 03 Apr. 2025, [International Magazine]
  English, Scientific journal
• 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, Apr. 2025, [International Magazine]
  English, Scientific journal, 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, 20 Mar. 2025, [International Magazine]
  English, Scientific journal
• 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, 18 Mar. 2025, [International Magazine]
  English, Scientific journal
• 農薬類によるグリア-ニューロン間相互作用の撹乱を介した新たな神経毒性機序の解明
  平野 哲史; 池中 良徳; 星 信彦; 田渕 圭章
  日本衛生学雑誌, 80, Suppl., S231, S231, (一社)日本衛生学会, Mar. 2025
  Japanese
• Effects of microplastics on seabird chicks: an experiment using pellets with and without chemical additives
  Koki Shigeishi; Rei Yamashita; Kosuke Tanaka; Mami Kazama; Naya Sena; Hideshige Takada; Yoshinori Ikenaka; Mayumi Ishizuka; Shiho Koyama; Ken Yoda; Yutaka Watanuki
  ORNITHOLOGICAL SCIENCE, 24, 1, 129, 145, Jan. 2025
  English, Scientific journal
• Neonicotinoid detection in rainwater in Japan
  Zanne Sandriati PUTRI; Toshiko SATO; Yared Beyene YOHANNES; Yoshinori IKENAKA; Masumi YAMAMURO
  Environmental Monitoring and Contaminants Research, 5, 57, 65, Japan Society for Environmental Chemistry, 2025
  Scientific journal
• 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, [International Magazine]
  English, Scientific journal
• 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, 2025, [Domestic magazines]
  English, Scientific journal
• 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, 2025, [Domestic magazines]
  English, Scientific journal
• 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, 04 Dec. 2024, [International Magazine]
  English, Scientific journal
• フィプロニル代謝物が誘導するミクログリアの活性化とニューロンとの相互作用の撹乱機序の解析
  平野 哲史; 池中 良徳; 星 信彦; 田渕 圭章
  日本内分泌撹乱物質学会研究発表会プログラム・抄録集, 26回, 41, 41, 日本内分泌撹乱物質学会, Dec. 2024
  Japanese
• クロチアニジン父性曝露による精子microRNAの発現変動と神経行動学的な次世代影響
  伊藤 槙子; 布引 沙利香; 吉本 彩乃; 万谷 洋平; 横山 俊史; 平野 哲史; 池中 良徳; 星 信彦
  日本内分泌撹乱物質学会研究発表会プログラム・抄録集, 26回, 47, 47, 日本内分泌撹乱物質学会, Dec. 2024
  Japanese
• ネオニコチノイド系農薬クロチアニジンの無毒性量(NOAEL)曝露による母性行動への継世代影響
  布引 沙利香; 伊藤 槙子; 吉本 彩乃; 森下 理奈子; 万谷 洋平; 横山 俊史; 平野 哲史; 池中 良徳; 星 信彦
  日本内分泌撹乱物質学会研究発表会プログラム・抄録集, 26回, 48, 48, 日本内分泌撹乱物質学会, Dec. 2024
  Japanese
• マウスにおけるフェニルピラゾール系農薬フィプロニルの胎子・新生子期曝露の次世代影響
  吉本 彩乃; 伊藤 槙子; 布引 沙利香; 万谷 洋平; 横山 俊史; 平野 哲史; 池中 良徳; 星 信彦
  日本内分泌撹乱物質学会研究発表会プログラム・抄録集, 26回, 49, 49, 日本内分泌撹乱物質学会, Dec. 2024
  Japanese
• 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, 14 Oct. 2024, [Domestic magazines]
  English, Scientific journal
• 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, Oct. 2024, [International Magazine]
  English, Scientific journal
• 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, 03 Sep. 2024, [Domestic magazines]
  English, Scientific journal
• 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, 21 Aug. 2024, [International Magazine]
  English, Scientific journal
• フィプロニル代謝物が引き起こすミクログリア-ニューロン間相互作用の撹乱メカニズムの解明
  平野 哲史; 池中 良徳; 星 信彦; 田渕 圭章
  The Journal of Toxicological Sciences, 49, Suppl., S98, S98, (一社)日本毒性学会, Jul. 2024
  Japanese
• Anticoagulant rodenticides exposure status among wild pit vipers (Protobothrops flavoviridis) and green anoles (Anolis carolinensis) in two Japanese Islands
  Yoshiya Yamamura; Shintaro Nakagawa; Mitsuki Kondo; So Shinya; Rio Doya; Masashi Koide; Yared Beyene Yohannes; Yoshinori Ikenaka; Mayumi Ishizuka; Shouta M. M. Nakayama
  EUROPEAN JOURNAL OF WILDLIFE RESEARCH, 70, 3, Jun. 2024
  English, Scientific journal
• 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, Jun. 2024, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, 29 May 2024, [International Magazine]
  English, Scientific journal, 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, 21 May 2024, [International Magazine]
  English, Scientific journal
• オオミズナギドリにおける血球と羽根の水銀濃度
  岩崎真由; 安積紗羅々; 石塚真由美; 池中良徳; 綿貫豊
  日本鳥学会誌, 73, 57, 65, May 2024, [Peer-reviewed]
  Japanese
• 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, May 2024, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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, 04 Apr. 2024, [International Magazine]
  English, Scientific journal
• 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, 13 Mar. 2024
  Scientific journal
• 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, 05 Mar. 2024, [International Magazine]
  English, Scientific journal, 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, 07 Feb. 2024, [International Magazine]
  English, Scientific journal, 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, 05 Feb. 2024, [Domestic magazines]
  English, Scientific journal
• 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, 05 Feb. 2024, [Domestic magazines]
  English, Scientific journal
• 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, Feb. 2024, [International Magazine]
  English, Scientific journal, 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, Feb. 2024
  Scientific journal
• 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, 23 Jan. 2024, [Domestic magazines]
  English, Scientific journal, 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
  Scientific journal
• 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, 29 Dec. 2023, [International Magazine]
  English, Scientific journal, 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, Nov. 2023, [International Magazine]
  English, Scientific journal, 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, Nov. 2023, [International Magazine]
  English, Scientific journal, 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, 31 Oct. 2023, [Domestic magazines]
  English, Scientific journal, 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, 04 Aug. 2023, [Domestic magazines]
  English, Scientific journal, 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, 27 Jul. 2023, [International Magazine]
  English, Scientific journal, 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, 09 Jun. 2023, [International Magazine]
  English, Scientific journal, 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, Jun. 2023
  Japanese
• 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, May 2023
  Japanese
• 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, May 2023
  Japanese
• 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, 20 Apr. 2023, [International Magazine]
  English, Scientific journal, 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, 11 Apr. 2023, [International Magazine]
  English, Scientific journal, 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, Apr. 2023, [International Magazine]
  English, Scientific journal, 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, Mar. 2023
  Japanese
• 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, Mar. 2023
  Japanese
• 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, Mar. 2023, [International Magazine]
  English, Scientific journal, 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, 01 Mar. 2023, [Domestic magazines]
  English, Scientific journal, 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, 28 Feb. 2023, [Domestic magazines]
  English, Scientific journal, 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, 02 Jan. 2023, [Domestic magazines]
  English, Scientific journal, 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
  English, 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, [International Magazine]
  English, Scientific journal, 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, Jan. 2023, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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, 13 Dec. 2022, [Peer-reviewed], [Invited], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal, 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, 10 Dec. 2022, [International Magazine]
  English, Scientific journal, 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, Dec. 2022, [International Magazine]
  English, Scientific journal, 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, 29 Nov. 2022, [International Magazine]
  English, Scientific journal, 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, 17 Nov. 2022, [International Magazine]
  English, Scientific journal, 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, 02 Nov. 2022, [Domestic magazines]
  English, Scientific journal, 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, 31 Oct. 2022, [International Magazine]
  English, Scientific journal, 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, 27 Oct. 2022, [International Magazine]
  English, Scientific journal, 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, 18 Oct. 2022, [International Magazine]
  English, Scientific journal, 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, 14 Oct. 2022, [International Magazine]
  English, Scientific journal, 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, Oct. 2022
• 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, Oct. 2022
  Japanese
• 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, 28 Sep. 2022, [International Magazine]
  English, Scientific journal, 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 &gt; 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 &gt; 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, 28 Sep. 2022, [International Magazine]
  English, Scientific journal, 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, Sep. 2022
  Japanese
• 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, Sep. 2022
  Japanese
• 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, Sep. 2022
  Japanese
• 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, Sep. 2022, [International Magazine]
  English, Scientific journal
• 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, Sep. 2022, [International Magazine]
  English, Scientific journal, 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, 15 Aug. 2022, [International Magazine]
  English, Scientific journal, 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, Aug. 2022
  Japanese
• 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, Aug. 2022
  Japanese
• 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, Aug. 2022
  Japanese
• 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, Aug. 2022, [International Magazine]
  English, Scientific journal, 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, 16 Jun. 2022, [International Magazine]
  English, Scientific journal, 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, 14 Jun. 2022, [International Magazine]
  English, Scientific journal, 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, 09 Jun. 2022, [International Magazine]
  English, Scientific journal, 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, 06 Jun. 2022, [International Magazine]
  English, Scientific journal, 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, 03 Jun. 2022, [International Magazine]
  English, Scientific journal, 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, Jun. 2022
  Japanese
• 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, Jun. 2022
  Japanese
• 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, 27 May 2022, [Domestic magazines]
  English, Scientific journal, 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, Apr. 2022, [International Magazine]
  English, Scientific journal, 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), 21 Mar. 2022, [International Magazine]
  English, Scientific journal, 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, Mar. 2022
  Scientific journal
• 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, Feb. 2022, [International Magazine]
  English, Scientific journal
• Wild Lizards as a Target of Heavy Metal Biomonitoring Focusing on Land Use Patterns; An Example from a Former Mining Site in Zambia
  DOYA Rio; NAKAYAMA Shouta M. M.; NAKATA Hokuto; KONDO Mitsuki; ZYAMBO Golden; MUZANDU Kaampwe; YABE John; IKENAKA Yoshinori; ISHIZUKA Mayumi
  Annual Meeting of the Japanese Society of Toxicology, 49.1, P-133, The Japanese Society of Toxicology, 2022
  Japanese, 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
  NIMAKO Collins; HIRAI Anri; ICHISE Takahiro; NAKAYAMA Shouta M.M.; ISHIZUKA Mayumi; IKENAKA Yoshinori
  Annual Meeting of the Japanese Society of Toxicology, 49.1, P-108, The Japanese Society of Toxicology, 2022
  Japanese, 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, [Domestic magazines]
  English, Scientific journal, 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, [International Magazine]
  English, Scientific journal, 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, 01 Jan. 2022, [International Magazine]
  English, Scientific journal
• 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, Dec. 2021, [International Magazine]
  English, Scientific journal
• 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, 01 Oct. 2021, [International Magazine]
  English, Scientific journal, 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, 01 Oct. 2021, [International Magazine]
  English, Scientific journal, 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, 17 Sep. 2021, [Domestic magazines]
  English, Scientific journal, 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, 16 Sep. 2021, [Domestic magazines]
  English, Scientific journal, 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, 11 Sep. 2021, [International Magazine]
  English, Scientific journal, 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), Sep. 2021
  Japanese
• 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, Sep. 2021
  English
• 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, 01 Sep. 2021, [International Magazine]
  English, Scientific journal, 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, 30 Aug. 2021, [International Magazine]
  English, Scientific journal, 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, 28 Aug. 2021, [International Magazine]
  English, Scientific journal
• 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, 15 Aug. 2021, [International Magazine]
  English, Scientific journal, 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, Aug. 2021, [International Magazine]
  English, Scientific journal, 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, Jul. 2021
  English
• 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, Jul. 2021, [International Magazine]
  English, Scientific journal, 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, 10 Jun. 2021, [International Magazine]
  English, Scientific journal
• 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, Jun. 2021
  Scientific journal
• 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, Jun. 2021, [International Magazine]
  English, Scientific journal, 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, 15 May 2021, [International Magazine]
  English, Scientific journal, 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, May 2021, [International Magazine]
  English, Scientific journal, 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, 24 Apr. 2021, [Domestic magazines]
  English, Scientific journal, 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, 09 Apr. 2021, [Domestic magazines]
  English, Scientific journal, 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, 03 Apr. 2021, [Domestic magazines]
  English, Scientific journal, 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, 03 Apr. 2021, [Domestic magazines]
  English, Scientific journal, 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, Apr. 2021
  Japanese
• 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, Apr. 2021, [International Magazine]
  English, Scientific journal
• 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, Mar. 2021, [International Magazine]
  English, Scientific journal, 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, Feb. 2021
  English, Scientific journal
• 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, Feb. 2021
  English, Scientific journal
• 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, 18 Jan. 2021, [International Magazine]
  English, Scientific journal, 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, 13 Jan. 2021, [International Magazine]
  English, Scientific journal, 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
  NIMAKO Collins; IKENAKA Yoshinori; AKOTO Osei; FUJIOKA Kazutoshi; TAIRA Kumiko; ARIZONO Koji; KATO Keisuke; TAKAHASHI Keisuke; NAKAYAMA Shouta M.M.; ICHISE Takahiro; ISHIZUKA Mayumi
  Annual Meeting of the Japanese Society of Toxicology, 48.1, P-154E, The Japanese Society of Toxicology, 2021
  Japanese, 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.
• Introduction: Cooperation with Mongolian University of Life Sciences in research activity
  Motohira Kodai; Dugar Delgermurun; Ikenaka Yoshinori; Nakayama Shouta; Pelden Bolormaa; Gendenpil Lkhamjav; Ishizuka Mayumi
  Proceedings of the Annual Meeting of Japan Society for Science Education, 45, 563, 564, Japan Society for Science Education, 2021
  Japanese, 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。
• Neurotoxicity of a pyrethroid pesticide deltamethrin mediated by imbalance of proteolytic systems
  HIRANO Tetsushi; SUZUKI Nihei; IKENAKA Yoshinori; HOSHI Nobuhiko; TABUCHI Yoshiaki
  Annual Meeting of the Japanese Society of Toxicology, 48, P, 2E, The Japanese Society of Toxicology, 2021
  Japanese,

  We investigated the mechanisms of neurotoxicity of a pyrethroid pesticide deltamethrin (DM) focusing on proteolytic systems. DM dose-dependently increased expression of autophagy markers LC3-II and p62 and induced apoptosis in the Neuro2a cells. The expression of mitochondria markers was decreased by DM and co-localized with LC3-II, which suggests the accumulation of autolysosomes containing damaged mitochondria. The amount of ubiquitinated protein was increased by DM while proteasome activities were decreased. These results revealed that DM induced neurotoxicity caused by mitophagy activation and proteasome inhibition.

• 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, [International Magazine]
  English, Scientific journal, 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, Jan. 2021, [International Magazine]
  English, Scientific journal, 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, Jan. 2021, [International Magazine]
  English, Scientific journal, 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, 17 Nov. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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, Nov. 2020, [International Magazine]
  English, Scientific journal, 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, Oct. 2020, [International Magazine]
  English, Scientific journal, 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, 18 Sep. 2020, [International Magazine]
  English, Scientific journal, 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, Sep. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, 19 Aug. 2020, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, 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, Aug. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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, 31 Jul. 2020, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, 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, Jun. 2020
  Japanese
• 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, Jun. 2020
  Japanese
• 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, Jun. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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 ι³C and ι⁵N 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, May 2020
  Scientific journal
• 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, May 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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, 01 Apr. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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, 24 Mar. 2020, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, 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, Mar. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, 24 Feb. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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, Feb. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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, Jan. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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, Jan. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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), Dec. 2019
  Japanese
• 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), Dec. 2019
  Japanese
• 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), Dec. 2019
  Japanese
• 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, Dec. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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, 15 Nov. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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, 14 Nov. 2019, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, 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, Nov. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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, 20 Oct. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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, Oct. 2019
  Scientific journal
• 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, Oct. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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, Sep. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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, Aug. 2019
  Japanese
• 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, 28 Jun. 2019, [Peer-reviewed]
  Scientific journal
• 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, Jun. 2019
  Japanese
• 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, Jun. 2019
  Japanese
• 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, Jun. 2019, [International Magazine]
  English, Scientific journal, 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, May 2019, [International Magazine]
  English, Scientific journal, 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.
  Yasuhiro Uno; Rika Takahira; Norie Murayama; Shunsuke Onozeki; Shu Kawamura; Shotaro Uehara; Yoshinori Ikenaka; Mayumi Ishizuka; Shinichi Ikushiro; Hiroshi Yamazaki
  Biochemical pharmacology, 163, 335, 344, May 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Characterization of function and genetic feature of UDP-glucuronosyltransferase in avian species.
  Yusuke K Kawai; So Shinya; Yoshinori Ikenaka; Aksorn Saengtienchai; Takamitsu Kondo; Wageh Sobhy Darwish; Shota M M Nakayama; Hazuki Mizukawa; Mayumi Ishizuka
  Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 217, 5, 14, Mar. 2019, [Peer-reviewed], [International Magazine]
  English
• 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, 28 Feb. 2019, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal
• Mechanism analysis of signal toxic effects of neonicotinoid pesticides on human neuroblastoma cells
  HIRANO Tetsushi; MINAGAWA Satsuki; FURUSAWA Yukihiro; YUNOKI Tatsuya; IKENAKA Yoshinori; YOKOYAMA Toshifumi; HOSHI Nobuhiko; TABUCHI Yoshiaki
  Annual Meeting of the Japanese Society of Toxicology, 46, P, 88E, The Japanese Society of Toxicology, 2019
  Japanese,

  [in Japanese]

• 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, Jan. 2019, [Peer-reviewed]
  Scientific journal
• 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, Jan. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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.
  Yasuhiro Uno; Rika Takahira; Norie Murayama; Yu Ishii; Yoshinori Ikenaka; Mayumi Ishizuka; Hiroshi Yamazaki; Shinichi Ikushiro
  Biochemical pharmacology, 155, 172, 181, Sep. 2018, [Peer-reviewed], [International Magazine]
  English
• 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).
  Hiroshi Ishibashi; Masaya Uchida; Keisuke Yoshimoto; Yuta Imamura; Ryoko Yamamoto; Yoshinori Ikenaka; Masahito Kawai; Nobuhiro Ichikawa; Yuji Takao; Nobuaki Tominaga; Yasuhiro Ishibashi; Koji Arizono
  Environmental pollution (Barking, Essex : 1987), 239, 281, 288, Aug. 2018, [Peer-reviewed], [International Magazine]
  English
• 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.
  Wihan Pheiffer; Nico J Wolmarans; Ruan Gerber; Yared B Yohannes; Yoshinori Ikenaka; Mayumi Ishizuka; Nico J Smit; Victor Wepener; Rialet Pieters
  The Science of the total environment, 628-629, 517, 527, 01 Jul. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, Jul. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, Jun. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, 30 Apr. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, Apr. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, 02 Mar. 2018, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal
• 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.
  Wageh Sobhy Darwish; Yoshinori Ikenaka; Shouta Nakayama; Hazuki Mizukawa; Lesa A Thompson; Mayumi Ishizuka
  Environmental science and pollution research international, 25, 7, 6320, 6328, Mar. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• The evolution of UDP-glycosyl/glucuronosyltransferase 1E (UGT1E) genes in bird lineages is linked to feeding habits but UGT2 genes is not.
  Yusuke K Kawai; Yoshinori Ikenaka; Mayumi Ishizuka; Akira Kubota
  PloS one, 13, 10, e0205266, 2018, [Peer-reviewed], [International Magazine]
  English
• 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), Dec. 2017, [Peer-reviewed]
  Japanese
• 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, Nov. 2017, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, 03 Oct. 2017, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, Oct. 2017, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, Sep. 2017, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, 01 Jul. 2017, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, Jun. 2017, [Peer-reviewed]
  Japanese
• 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, 20 Apr. 2017, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal
• 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, 08 Apr. 2017, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal
• 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, Feb. 2017, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, 10 Jan. 2017, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, Jan. 2017, [Peer-reviewed]
  English, Scientific journal
• 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, Jan. 2017, [Peer-reviewed]
  English, Scientific journal
• 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, [Peer-reviewed], [Domestic magazines]
  Japanese, Scientific journal
• 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, Jan. 2017, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• The African hedgehog (Atelerix albiventris): Low phase I and phase II metabolism activities.
  Aksorn Saengtienchai; Yoshinori Ikenaka; Nesta Bortey-Sam; Usuma Jermnark; Hazuki Mizukawa; Yusuke K Kawai; Shouta M M Nakayama; Mayumi Ishizuka
  Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 190, 38, 47, Dec. 2016, [Peer-reviewed], [International Magazine]
  English
• Excretion of polycyclic aromatic hydrocarbon metabolites (OH-PAHs) in cattle urine in Ghana.
  Nesta Bortey-Sam; Yoshinori Ikenaka; Osei Akoto; Shouta M M Nakayama; Jemima Marfo; Aksorn Saengtienchai; Hazuki Mizukawa; Mayumi Ishizuka
  Environmental pollution (Barking, Essex : 1987), 218, 331, 337, Nov. 2016, [Peer-reviewed], [International Magazine]
  English
• Heavy metals and metalloid accumulation in livers and kidneys of wild rats around gold-mining communities in Tarkwa, Ghana
  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, 31 Jul. 2016
  Scientific journal
• Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats.
  Yoshihiro Nishiyama; Shouta M M Nakayama; Kensuke P Watanabe; Yusuke K Kawai; Marumi Ohno; Yoshinori Ikenaka; Mayumi Ishizuka
  The Journal of veterinary medical science, 78, 4, 675, 80, 03 May 2016, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal
• Bioaccumulation and human health risk assessment of DDT and other organochlorine pesticides in an apex aquatic predator from a premier conservation area.
  Ruan Gerber; Nico J Smit; Johan H J Van Vuren; Shouta M M Nakayama; Yared B Yohannes; Yoshinori Ikenaka; Mayumi Ishizuka; Victor Wepener
  The Science of the total environment, 550, 522, 533, 15 Apr. 2016, [Peer-reviewed], [International Magazine]
  English
• Distribution and health risk assessment of organochlorine pesticides (OCPs) residue in edible cattle tissues from northeastern part of Egypt: High accumulation level of OCPs in tongue.
  Abdallah Fikry A Mahmoud; Yoshinori Ikenaka; Yared B Yohannes; Wageh S Darwish; Elsaid A Eldaly; Alaa Eldin M A Morshdy; Shouta M M Nakayama; Hazuki Mizukawa; Mayumi Ishizuka
  Chemosphere, 144, 1365, 71, Feb. 2016, [Peer-reviewed], [International Magazine]
  English
• β-carotene and retinol contents in the meat of herbivorous ungulates with a special reference to their public health importance.
  Wageh Sobhy Darwish; Yoshinori Ikenaka; Alaa Eldin Morshdy; Kamal Ibrahim Eldesoky; Shouta Nakayama; Hazuki Mizukawa; Mayumi Ishizuka
  The Journal of veterinary medical science, 78, 2, 351, 4, Feb. 2016, [Peer-reviewed], [Domestic magazines]
  English
• Organohalogen Compounds in Pet Dog and Cat: Do Pets Biotransform Natural Brominated Products in Food to Harmful Hydroxlated Substances?
  Hazuki Mizukawa; Kei Nomiyama; Susumu Nakatsu; Hisato Iwata; Jean Yoo; Akira Kubota; Miyuki Yamamoto; Mayumi Ishizuka; Yoshinori Ikenaka; Shouta M M Nakayama; Tatsuya Kunisue; Shinsuke Tanabe
  Environmental science & technology, 50, 1, 444, 52, 05 Jan. 2016, [Peer-reviewed], [International Magazine]
  English
• 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, Jan. 2016, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Constitutive Effects of Lead on Aryl Hydrocarbon Receptor Gene Battery and Protection by β-carotene and Ascorbic Acid in Human HepG2 Cells.
  Wageh S Darwish; Yoshinori Ikenaka; Shouta M M Nakayama; Hazuki Mizukawa; Mayumi Ishizuka
  Journal of food science, 81, 1, T275-81, 81, Jan. 2016, [Peer-reviewed], [International Magazine]
  English
• Application of a Sediment Quality Index for the assessment and monitoring of metals and organochlorines in a premier conservation area.
  Ruan Gerber; Nico J Smit; Johan H J van Vuren; Shouta M M Nakayama; Yared B Yohannes; Yoshinori Ikenaka; Mayumi Ishizuka; Victor Wepener
  Environmental science and pollution research international, 22, 24, 19971, 89, Dec. 2015, [Peer-reviewed], [International Magazine]
  English
• Accumulation properties of inorganic mercury and organic mercury in the red-crowned crane Grus japonensis in east Hokkaido, Japan.
  Hiroki Teraoka; Erika Okamoto; Moe Kudo; Shouta M M Nakayama; Yoshinori Ikenaka; Mayumi Ishizuka; Tetsuya Endo; Takio Kitazawa; Takeo Hiraga
  Ecotoxicology and environmental safety, 122, 557, 64, Dec. 2015, [Peer-reviewed], [International Magazine]
  English
• Mutagenicity of modelled-heat-treated meat extracts: Mutagenicity assay, analysis and mechanism of mutagenesis.
  Wageh Sobhy Darwish; Yoshinori Ikenaka; Shouta Nakayama; Hazuki Mizukawa; Mayumi Ishizuka
  The Japanese journal of veterinary research, 63, 4, 173, 82, Nov. 2015, [Peer-reviewed], [Domestic magazines]
  English
• Characterization and tissue distribution of conjugated metabolites of pyrene in the rat.
  Aksorn Saengtienchai; Yoshinori Ikenaka; Wageh Sobhy Darwish; Shouta M M Nakayama; Hazuki Mizukawa; Mayumi Ishizuka
  The Journal of veterinary medical science, 77, 10, 1261, 7, Oct. 2015, [Peer-reviewed], [Domestic magazines]
  English
• Uridine Diphosphate-Glucuronosyltransferase (UGT) Xenobiotic Metabolizing Activity and Genetic Evolution in Pinniped Species.
  Mayu Kakehi; Yoshinori Ikenaka; Shouta M M Nakayama; Yusuke K Kawai; Kensuke P Watanabe; Hazuki Mizukawa; Kei Nomiyama; Shinsuke Tanabe; Mayumi Ishizuka
  Toxicological sciences : an official journal of the Society of Toxicology, 147, 2, 360, 9, Oct. 2015, [Peer-reviewed], [International Magazine]
  English
• 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, Oct. 2015, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, Oct. 2015, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, 65, 11 Sep. 2015, [Peer-reviewed], [International Magazine]
  English
• 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, Sep. 2015, [Peer-reviewed]
  English, Scientific journal
• 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, Aug. 2015, [Peer-reviewed]
  English, Scientific journal
• Accumulation of Heavy Metals and Metalloid in Foodstuffs from Agricultural Soils around Tarkwa Area in Ghana, and Associated Human Health Risks.
  Nesta Bortey-Sam; Shouta M M Nakayama; Osei Akoto; Yoshinori Ikenaka; Julius N Fobil; Elvis Baidoo; Hazuki Mizukawa; Mayumi Ishizuka
  International journal of environmental research and public health, 12, 8, 8811, 27, 28 Jul. 2015, [Peer-reviewed], [International Magazine]
  English
• 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, Jul. 2015, [Peer-reviewed]
  English, Scientific journal
• Health risk assessment of heavy metals and metalloid in drinking water from communities near gold mines in Tarkwa, Ghana.
  Nesta Bortey-Sam; Shouta M M Nakayama; Yoshinori Ikenaka; Osei Akoto; Elvis Baidoo; Hazuki Mizukawa; Mayumi Ishizuka
  Environmental monitoring and assessment, 187, 7, 397, 397, Jul. 2015, [Peer-reviewed], [International Magazine]
  English
• Metabolic Activation of Heterocyclic Amines and Expression of Xenobiotic-Metabolizing Enzymes in the Gastrointestinal Tract of Rats.
  Wageh S Darwish; Shouta M M Nakayama; Yuumi Itotani; Marumi Ohno; Yoshinori Ikenaka; Mayumi Ishizuka
  Journal of food science, 80, 7, T1627-32, 32, Jul. 2015, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Levels, potential sources and human health risk of polycyclic aromatic hydrocarbons (PAHs) in particulate matter (PM(10)) in Kumasi, Ghana.
  Nesta Bortey-Sam; Yoshinori Ikenaka; Osei Akoto; Shouta M M Nakayama; Yared Beyene Yohannes; Elvis Baidoo; Hazuki Mizukawa; Mayumi Ishizuka
  Environmental science and pollution research international, 22, 13, 9658, 67, Jul. 2015, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Are red gourami (Colisa labiosa) low xenobiotic metabolizers? Elucidation of in vivo pharmacokinetics of pyrene as a model substrate.
  Yoshinori Ikenaka; Shouta M M Nakayama; Mami Oguri; Aksorn Saengtienchai; Hazuki Mizukawa; Jun Kobayashi; Wageh Sobhy Darwish; Mayumi Ishizuka
  Environmental toxicology and pharmacology, 39, 3, 1148, 53, May 2015, [Peer-reviewed], [International Magazine]
  English
• Relationship between Urinary N-Desmethyl-Acetamiprid and Typical Symptoms including Neurological Findings: A Prevalence Case-Control Study.
  Jemima Tiwaa Marfo; Kazutoshi Fujioka; Yoshinori Ikenaka; Shouta M M Nakayama; Hazuki Mizukawa; Yoshiko Aoyama; Mayumi Ishizuka; Kumiko Taira
  PloS one, 10, 11, e0142172, 2015, [Peer-reviewed], [International Magazine]
  English
• Human health risks from metals and metalloid via consumption of food animals near gold mines in Tarkwa, Ghana: estimation of the daily intakes and target hazard quotients (THQs).
  Nesta Bortey-Sam; Shouta M M Nakayama; Yoshinori Ikenaka; Osei Akoto; Elvis Baidoo; Yared Beyene Yohannes; Hazuki Mizukawa; Mayumi Ishizuka
  Ecotoxicology and environmental safety, 111, 160, 7, Jan. 2015, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 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, Jan. 2015, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Occurrence, distribution, sources and toxic potential of polycyclic aromatic hydrocarbons (PAHs) in surface soils from the Kumasi Metropolis, Ghana.
  Nesta Bortey-Sam; Yoshinori Ikenaka; Shouta M M Nakayama; Osei Akoto; Yared Beyene Yohannes; Elvis Baidoo; Hazuki Mizukawa; Mayumi Ishizuka
  The Science of the total environment, 496, 471, 478, 15 Oct. 2014, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• TCDD‑induced chick cardiotoxicity is abolished by a selective cyclooxygenase‑2 (COX‑2) inhibitor NS398.
  Nozomi Fujisawa; Shouta M M Nakayama; Yoshinori Ikenaka; Mayumi Ishizuka
  Archives of toxicology, 88, 9, 1739, 1748, Sep. 2014, [Peer-reviewed], [International Magazine]
  English
• Identification of interspecific differences in phase II reactions: determination of metabolites in the urine of 16 mammalian species exposed to environmental pyrene.
  Aksorn Saengtienchai; Yoshinori Ikenaka; Shouta M M Nakayama; Hazuki Mizukawa; Mayu Kakehi; Nesta Bortey-Sam; Wageh Sobhy Darwish; Toshio Tsubota; Masanori Terasaki; Amnart Poapolathep; Mayumi Ishizuka
  Environmental toxicology and chemistry, 33, 9, 2062, 9, Sep. 2014, [Peer-reviewed], [International Magazine]
  English
• 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, Sep. 2014, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Apoptosis and gene expression in the developing mouse brain of fusarenon-X-treated pregnant mice.
  Samak Sutjarit; Shota M M Nakayama; Yoshinori Ikenaka; Mayumi Ishizuka; Wijit Banlunara; Worawut Rerkamnuaychoke; Susumu Kumagai; Amnart Poapolathep
  Toxicology letters, 229, 1, 292, 302, 17 Aug. 2014, [Peer-reviewed], [International Magazine]
  English
• 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, Aug. 2014, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Contamination status and possibility of toxic effects of co-planar polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and dichlorodiphenyltrichloroethane in large japanese field mouse (Apodemus speciosus) collected from Hokkaido and Aomori.
  Hazuki Mizukawa; Yoshinori Ikenaka; Shouta M M Nakayama; Kentaro Q Sakamoto; Shoichi Fujita; Mayumi Ishizuka
  The Japanese journal of veterinary research, 62, 3, 107, 15, Aug. 2014, [Peer-reviewed], [Domestic magazines]
  English
• Contamination status and accumulation characteristics of metals and a metalloid in birds on Teuri Island, Hokkaido, Japan.
  Chihiro Ishii; Yoshinori Ikenaka; Shouta M M Nakayama; Yuya Suzuki; Yutaka Watanuki; Yuji Watanabe; Yared Beyene Yohannes; Hazuki Mizukawa; Mayumi Ishizuka
  The Japanese journal of veterinary research, 62, 3, 143, 9, Aug. 2014, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal
• An overview on mycotoxin contamination of foods in Africa.
  Wageh Sobhy Darwish; Yoshinori Ikenaka; Shouta M M Nakayama; Mayumi Ishizuka
  The Journal of veterinary medical science, 76, 6, 789, 97, Jun. 2014, [Peer-reviewed], [Domestic magazines]
  English
• 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, May 2014, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• The effect of copper on the mRNA expression profile of xenobiotic-metabolizing enzymes in cultured rat H4-II-E cells.
  Wageh Sobhy Darwish; Yoshinori Ikenaka; Shouta Nakayama; Mayumi Ishizuka
  Biological trace element research, 158, 2, 243, 8, May 2014, [Peer-reviewed], [International Magazine]
  English
• Toxicokinetics and tissue depletion of Fusarenon-X and its metabolite nivalenol in piglets.
  Thanit Saengtienchai; Saranya Poapolathep; Supaporn Isariyodom; Yoshinori Ikenaka; Mayumi Ishizuka; Amnart Poapolathep
  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 66, 307, 12, Apr. 2014, [Peer-reviewed], [International Magazine]
  English
• 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, Feb. 2014, [Peer-reviewed]
  English, Scientific journal
• 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, 01 Jan. 2014
  In book
• 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, Jan. 2014, [Peer-reviewed]
  English
• Dioxin sensitivity-related two critical amino acids of arylhydrocarbon receptor may not correlate with the taxonomy or phylogeny in avian species.
  Nozomi Fujisawa; Yusuke K Kawai; Shouta M M Nakayama; Yoshinori Ikenaka; Hideaki Yamamoto; Mayumi Ishizuka
  The Journal of veterinary medical science, 75, 12, 1577, 83, 30 Dec. 2013, [Peer-reviewed], [Domestic magazines]
  English
• 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, Dec. 2013, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Repeated treatment with furazolidone induces multiple cytochrome p450-related activities in chicken liver, but not in rat liver.
  Nobuo Sasaki; Tomoyuki Matumoto; Yoshinori Ikenaka; Shouta M M Nakayama; Mayumi Ishizuka; Akio Kazusaka; Shoichi Fujita
  The Journal of veterinary medical science, 75, 11, 1497, 502, Nov. 2013, [Peer-reviewed], [Domestic magazines]
  English
• De novo sequence analysis of cytochrome P450 1-3 genes expressed in ostrich liver with highest expression of CYP2G19.
  Yusuke K Kawai; Kensuke P Watanabe; Akihiro Ishii; Aiko Ohnuma; Hirofumi Sawa; Yoshinori Ikenaka; Mayumi Ishizuka
  Comparative biochemistry and physiology. Part D, Genomics & proteomics, 8, 3, 201, 8, Sep. 2013, [Peer-reviewed], [International Magazine]
  English
• Characterization of phase-II conjugation reaction of polycyclic aromatic hydrocarbons in fish species: unique pyrene metabolism and species specificity observed in fish species.
  Yoshinori Ikenaka; Mami Oguri; Aksorn Saengtienchai; Shouta M M Nakayama; Shigeho Ijiri; Mayumi Ishizuka
  Environmental toxicology and pharmacology, 36, 2, 567, 578, Sep. 2013, [Peer-reviewed], [International Magazine]
  English
• Accumulation and biological effects of metals in wild rats in mining areas of Zambia.
  Shouta M M Nakayama; Yoshinori Ikenaka; Kyohei Hamada; Kaampwe Muzandu; Kennedy Choongo; John Yabe; Takashi Umemura; Mayumi Ishizuka
  Environmental monitoring and assessment, 185, 6, 4907, 18, Jun. 2013, [Peer-reviewed], [International Magazine]
  English
• 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, May 2013, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Antibiotic residues in food: the African scenario.
  Wageh Sobhy Darwish; Elsaid A Eldaly; Mohamed Tharwat El-Abbasy; Yoshinori Ikenaka; Shouta Nakayama; Mayumi Ishizuka
  The Japanese journal of veterinary research, 61 Suppl, S13-22, 22, Feb. 2013, [Peer-reviewed], [Domestic magazines]
  English
• Biological responses of xenobiotic metabolizing enzymes to lead exposure in cultured H4IIE rat cells.
  Wageh Sobhy Darwish; Yoshinori Ikenaka; Mayumi Ishizuka
  The Japanese journal of veterinary research, 61 Suppl, S48-53, 53, Feb. 2013, [Peer-reviewed], [Domestic magazines]
  English
• Determination of organochlorine pesticides (OCPs) in the edible offal of Egyptian buffalo.
  Abdallah Fikry A Mahmoud; Wageh Sobhy Darwish; Alaa Eldin M A Morshdy; Elsaid A Eldaly; Yoshinori Ikenaka; Mayumi Ishizuka
  The Japanese journal of veterinary research, 61 Suppl, S58-63, 63, Feb. 2013, [Peer-reviewed], [Domestic magazines]
  English
• Distribution of metals in organs of Clarias gariepinus, Heterobranchus bidorsalis, and Chrysichthys nigrodigitatus from the Offin River at Dunkwa-on-Offin, Ghana.
  Jemima T Marfo; Osei Akoto; Shouta M M Nakayama; Elvis Baidoo; Yoshinori Ikenaka; Mayumi Ishizuka
  The Japanese journal of veterinary research, 61 Suppl, S69-71, 71, Feb. 2013, [Peer-reviewed], [Domestic magazines]
  English
• Determination of benzo[a]pyrene levels in ambient air and the source of polycyclic aromatic hydrocarbons using a diagnostic ratio method in Ghana.
  Nesta Bortey-Sam; Osei Akoto; Yoshinori Ikenaka; Shouta M M Nakayama; Mayumi Ishizuka
  The Japanese journal of veterinary research, 61 Suppl, S72-4, 4, Feb. 2013, [Peer-reviewed], [Domestic magazines]
  English
• Heavy metal pollution in Japanese seabirds.
  Chihiro Ishii; Yoshinori Ikenaka; Shouta M M Nakayama; Yuya Suzuki; Yutaka Watanuki; Yuji Watanabe; Masa-aki Fukuwaka; Yared B Yohannes; Yusuke K Kawai; Mayumi Ishizuka
  The Japanese journal of veterinary research, 61 Suppl, S75-6, 6, Feb. 2013, [Peer-reviewed], [Domestic magazines]
  English
• Metabolism of pyrene, a polycyclic aromatic hydrocarbon in freshwater turtles.
  Balazs Oroszlany; Yoshinori Ikenaka; Aksorn Saengtiengchan; Mami Oguri; Shouta M M Nakayama; Mayumi Ishizuka
  The Japanese journal of veterinary research, 61 Suppl, S77-8, 8, Feb. 2013, [Peer-reviewed], [Domestic magazines]
  English
• Metal contaminated soil from mining area caused metal accumulation and biological responses in rats.
  Shouta M M Nakayama; Yoshinori Ikenaka; Kaampwe Muzandu; Kennedy Choongo; John Yabe; Takashi Umemura; Mayumi Ishizuka
  The Japanese journal of veterinary research, 61 Suppl, S79-81, 81, Feb. 2013, [Peer-reviewed], [Domestic magazines]
  English
• In vitro diazepam metabolism in horses.
  Aki Hayami; Wageh Sobhy Darwish; Yoshinori Ikenaka; Shouta M M Nakayama; Mayumi Ishizuka
  The Japanese journal of veterinary research, 61 Suppl, S82-4, 4, Feb. 2013, [Peer-reviewed], [Domestic magazines]
  English
• 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
  The Journal of toxicological sciences, 38, 1, 131, 6, Feb. 2013, [Peer-reviewed], [Domestic magazines]
  English
• 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, Feb. 2013, [Peer-reviewed]
  English, Scientific journal
• A novel mutation in VKORC1 and its effect on enzymatic activity in Japanese warfarin-resistant rats.
  Kazuyuki D Tanaka; Yusuke K Kawai; Yoshinori Ikenaka; Tsunehito Harunari; Tsutomu Tanikawa; Shoichi Fujita; Mayumi Ishizuka
  The Journal of veterinary medical science, 75, 2, 135, 9, Feb. 2013, [Peer-reviewed], [Domestic magazines]
  English
• Geographic information system-based source estimation of copper pollution in Lake Itezhi-tezhi and metal-accumulation profiles in Oreochromis spp. from both field and laboratory studies.
  Shouta M M Nakayama; Yoshinori Ikenaka; Kaampwe Muzandu; Kennedy Choongo; John Yabe; Taro Muroya; Shigeho Ijiri; Masao Minagawa; Takashi Umemura; Mayumi Ishizuka
  Archives of environmental contamination and toxicology, 64, 1, 119, 29, Jan. 2013, [Peer-reviewed], [International Magazine]
  English
• 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, Jan. 2013, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Avian cytochrome P450 (CYP) 1-3 family genes: isoforms, evolutionary relationships, and mRNA expression in chicken liver.
  Kensuke P Watanabe; Yusuke K Kawai; Yoshinori Ikenaka; Minami Kawata; Shin-Ichi Ikushiro; Toshiyuki Sakaki; Mayumi Ishizuka
  PloS one, 8, 9, e75689, 2013, [Peer-reviewed], [International Magazine]
  English
• Cytochrome P450 3A mRNA expression along goat and rat gastrointestinal tracts.
  Dominic Mureithi; Wageh Sobhy Darwish; Yoshinori Ikenaka; Laetitia Kanja; Mayumi Ishizuka
  The Japanese journal of veterinary research, 60, 4, 205, 10, Nov. 2012, [Peer-reviewed], [Domestic magazines]
  English
• 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, Oct. 2012, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal
• Effects of environmental lead contamination on cattle in a lead/zinc mining area: changes in cattle immune systems on exposure to lead in vivo and in vitro.
  Yoshinori Ikenaka; Shouta M M Nakayama; Taro Muroya; John Yabe; Satoru Konnai; Wageh Sobhy Darwish; Kaampwe Muzandu; Kennedy Choongo; Geoffrey Mainda; Hiroki Teraoka; Takashi Umemura; Mayumi Ishizuka
  Environmental toxicology and chemistry, 31, 10, 2300, 5, Oct. 2012, [Peer-reviewed], [International Magazine]
  English
• The nucleotide sequence of metallothioneins (MT) in liver of the Kafue lechwe (Kobus leche kafuensis) and their potential as biomarkers of heavy metal pollution of the Kafue River.
  Ethel M'kandawire; Michelo Syakalima; Kaampwe Muzandu; Girja Pandey; Martin Simuunza; Shouta M M Nakayama; Yusuke K Kawai; Yoshinori Ikenaka; Mayumi Ishizuka
  Gene, 506, 2, 310, 6, 15 Sep. 2012, [Peer-reviewed], [International Magazine]
  English
• 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, 15 Aug. 2012, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Metal and metalloid levels and bio-accumulation characteristics in soil, sediment, land plants and hippopotami (Hippopotamus amphibius L) from the South Luangwa National Park, Zambia.
  Shouta M M Nakayama; Yoshinori Ikenaka; Kaampwe Muzandu; Kennedy Choongo; Ethel M'kandawire; Jun Yasuda; Mayumi Ishizuka
  Ecotoxicology and environmental safety, 80, 333, 8, Jun. 2012, [Peer-reviewed], [International Magazine]
  English
• All-trans retinoic acid inhibits the recruitment of ARNT to DNA, resulting in the decrease of CYP1A1 mRNA expression in HepG2 cells.
  Marumi Ohno; Yoshinori Ikenaka; Mayumi Ishizuka
  Biochemical and biophysical research communications, 417, 1, 484, 9, 06 Jan. 2012, [Peer-reviewed], [International Magazine]
  English
• Cross-talks between heavy metals and xenobiotics metabolizing enzymes
  DARWISH Wageh S.; IKENAKA Yoshinori; ISHIZUKA Mayumi
  Annual Meeting of the Japanese Society of Toxicology, 39, O, 6, The Japanese Society of Toxicology, 2012
  Japanese, [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
  Annual Meeting of the Japanese Society of Toxicology, 39, AP, 223, The Japanese Society of Toxicology, 2012
  Japanese, [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
  Annual Meeting of the Japanese Society of Toxicology, 39, P, 125, The Japanese Society of Toxicology, 2012
  Japanese, [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.
  Marumi Ohno; Yoshinori Ikenaka; Mayumi Ishizuka
  Journal of biochemical and molecular toxicology, 26, 1, 16, 22, Jan. 2012, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Phase-II conjugation ability for PAH metabolism in amphibians: characteristics and inter-species differences.
  Haruki Ueda; Yoshinori Ikenaka; Shouta M M Nakayama; Tomoko Tanaka-Ueno; Mayumi Ishizuka
  Aquatic toxicology (Amsterdam, Netherlands), 105, 3-4, 337, 43, Oct. 2011, [Peer-reviewed], [International Magazine]
  English
• 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, Aug. 2011, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Astaxanthin can alter CYP1A-dependent activities via two different mechanisms: induction of protein expression and inhibition of NADPH P450 reductase dependent electron transfer.
  Marumi Ohno; Wageh S Darwish; Yoshinori Ikenaka; Wataru Miki; Mayumi Ishizuka
  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 49, 6, 1285, 91, Jun. 2011, [Peer-reviewed], [International Magazine]
  English
• Metal and metalloid contamination in roadside soil and wild rats around a Pb-Zn mine in Kabwe, Zambia.
  Shouta M M Nakayama; Yoshinori Ikenaka; Kyohei Hamada; Kaampwe Muzandu; Kennedy Choongo; Hiroki Teraoka; Naoharu Mizuno; Mayumi Ishizuka
  Environmental pollution (Barking, Essex : 1987), 159, 1, 175, 181, Jan. 2011, [Peer-reviewed], [International Magazine]
  English
• Carotenoids as regulators for inter-species difference in cytochrome P450 1A expression and activity in ungulates and rats.
  Wageh S Darwish; Yoshinori Ikenaka; Marumi Ohno; Elsaid A Eldaly; Mayumi Ishizuka
  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 48, 11, 3201, 8, Nov. 2010, [Peer-reviewed], [International Magazine]
  English
• 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, Sep. 2010, [Peer-reviewed]
  English, Scientific journal
• 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
  The Journal of veterinary medical science, 72, 9, 1237, 41, Sep. 2010, [Peer-reviewed], [Domestic magazines]
  English
• Heavy metal accumulation in lake sediments, fish (Oreochromis niloticus and Serranochromis thumbergi), and crayfish (Cherax quadricarinatus) in Lake Itezhi-tezhi and Lake Kariba, Zambia.
  Shouta M M Nakayama; Yoshinori Ikenaka; Kaampwe Muzandu; Kennedy Choongo; Balazs Oroszlany; Hiroki Teraoka; Naoharu Mizuno; Mayumi Ishizuka
  Archives of environmental contamination and toxicology, 59, 2, 291, 300, Aug. 2010, [Peer-reviewed], [International Magazine]
  English
• Metabolic activation of heterocyclic amines and expression of CYP1A1 in the tongue.
  Mami Takiguchi; Wageh S Darwish; Yoshinori Ikenaka; Marumi Ohno; Mayumi Ishizuka
  Toxicological sciences : an official journal of the Society of Toxicology, 116, 1, 79, 91, Jul. 2010, [Peer-reviewed], [International Magazine]
  English
• Comparison of warfarin sensitivity between rat and bird species.
  Kensuke P Watanabe; Aksorn Saengtienchai; Kazuyuki D Tanaka; Yoshinori Ikenaka; Mayumi Ishizuka
  Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 152, 1, 114, 9, Jun. 2010, [Peer-reviewed], [International Magazine]
  English
• The CYP1D subfamily of genes in mammals and other vertebrates.
  Yusuke K Kawai; Yoshinori Ikenaka; Shoichi Fujita; Mayumi Ishizuka
  Mammalian genome : official journal of the International Mammalian Genome Society, 21, 5-6, 320, 9, Jun. 2010, [Peer-reviewed], [International Magazine]
  English
• 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
  The Journal of veterinary medical science, 72, 5, 561, 6, 5, May 2010, [Peer-reviewed], [Domestic magazines]
  English, 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, May 2010, [Peer-reviewed]
  English, Scientific journal
• Expression and sequence of CYP1A1 in the camel.
  Wageh Sobhy Darwish; Alaa Eldin Morshdy; Yoshinori Ikenaka; Zein Shaban Ibrahim; Shoichi Fujita; Mayumi Ishizuka
  The Journal of veterinary medical science, 72, 2, 221, 4, 2, Feb. 2010, [Peer-reviewed], [Domestic magazines]
  English, 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, Feb. 2010, [Peer-reviewed]
  English, Scientific journal
• Protective effect of Pleurotus cornucopiae mushroom extract on carbon tetrachloride-induced hepatotoxicity.
  Bohi Khlood M El; Yoshiharu Hashimoto; Kaampwe Muzandu; Yoshinori Ikenaka; Zein Shaban Ibrahim; Akio Kazusaka; Shoichi Fujita; Mayumi Ishizuka
  The Japanese journal of veterinary research, 57, 2, 109, 18, Aug. 2009, [Peer-reviewed], [Domestic magazines]
  English
• Antibiotic furazolidone induces CYP1A but not CYP2E1 subfamily in rat liver.
  Nobuo Sasaki; Noriaki Sakai; Yoshinori Ikenaka; Tomomi Kamiya; Min Heewon; Kentaro Q Sakamoto; Mayumi Ishizuka; Shoichi Fujita
  The Journal of veterinary medical science, 70, 3, 223, 6, 3, Mar. 2008, [Peer-reviewed], [Domestic magazines]
  English, 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.
  Yoshinori Ikenaka; Masumi Ishizaka; Heesoo Eun; Yuichi Miyabara
  Biochemical and biophysical research communications, 360, 2, 490, 5, 24 Aug. 2007, [Peer-reviewed], [International Magazine]
  English
• Metabolism of pyrene by aquatic crustacean, Daphnia magna.
  Yoshinori Ikenaka; Heesoo Eun; Masumi Ishizaka; Yuichi Miyabara
  Aquatic toxicology (Amsterdam, Netherlands), 80, 2, 158, 65, 16 Nov. 2006, [Peer-reviewed], [International Magazine]
  English
• Estimation of sources and inflow of dioxins and polycyclic aromatic hydrocarbons from the sediment core of Lake Suwa, Japan.
  Yoshinori Ikenaka; Heesoo Eun; Eiki Watanabe; Fujio Kumon; Yuichi Miyabara
  Environmental pollution (Barking, Essex : 1987), 138, 3, 529, 37, 3, Dec. 2005, [Peer-reviewed], [International Magazine]
  English, 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.

• DRUG METABOLISM AND PHARMACOKINETICS 61 (2025) 101173 ASSESSMENT OF UNINTENTIONAL EFFECTS ON ENDANGERED SPECIES ENDEMIC TO THE BONIN ISLANDS CAUSED BY DEPLOYMENT OF ANTICOAGULANT RODENTICIDE
  Masashi Koide; Yusuke Kawai; Mitsuki Kondo; Yoshiya Odaya; Kazuo Horikoshi; Hajime Suzuki; Takashi Nagamine; Yamiko Nakaya; Yoshinori Ikenaka; Mayumi Ishizuka; Shouta Nakayama, DRUG METABOLISM AND PHARMACOKINETICS, 61, Jun. 2025
  English, Summary international conference
• Inter-species variation in iron stable isotope ratios and their association with hepatic ferritin in vertebrates
  長谷川菜々子; 板井啓明; 高橋嘉夫; 伊地知雄太; 柏原輝彦; YOHANNES Yared B.; 国末達也; 小笠原浩平; 徳長ゆり香; 池中良徳; 池中良徳; NDASHE Kunda; KATABA Andrew; 銅谷理緒; 小竹皓貴; 小竹皓貴; 乘本裕明; 乘本裕明; 中山翔太; 中山翔太; 石塚真由美, Biomedical Research on Trace Elements (Web), 36, S1, 2025
• Comparison of sensitivity of avian aminolevulinic acid dehydratase to lead exposure
  丸山瑞貴; 渡邊有希子; 石井千尋; 齊藤慶輔; 牛根奈々; 伊藤真輝; 飯間裕子; 中谷裕美子; 長嶺隆; 銅谷理緒; 小笠原浩平; 池中良徳; BEYENE Yared; 石塚真由美; 中山翔太, 日本野生動物医学会大会・講演要旨集, 30th, 2024
• 鉛曝露に対するヘム合成系酵素の感受性の鳥類種差とその決定要因の検討
  丸山瑞貴; 渡邊有希子; 石井千尋; 齊藤慶輔; 牛根奈々; 伊藤真輝; 銅谷理緒; 小笠原浩平; 池中良徳; ヤレド ベイェネ; 石塚真由美; 中山翔太, 日本鳥学会大会講演要旨集, 2024 (CD-ROM), 2024
• Establishment of a drug deployment system for the treatment of high pathogenicity avian influenza virus infections in rare birds: efforts towards biodiversity conservation and promoting proper use of medications
  迫田義博; 迫田義博; 日尾野隆大; 日尾野隆大; 池中良徳; 池中良徳, 日本野生動物医学会大会・講演要旨集, 30th, 2024
• Pharmacokinetic analysis of baloxavir marboxil in captive rare birds to establish the treatment protocol against high pathogenicity avian influenza virus infection
  島津陽; 三木万梨子; 尾原涼; 中谷裕美子; 長嶺隆; 吉本悠人; 林万里菜; 井出いづみ; 見浦沙耶子; 平栗祐子; 加来雅人; 豊田恒介; 尾崎美樹; 日尾野隆大; 日尾野隆大; 磯田典和; 磯田典和; 宍戸貴雄; 池中良徳; 迫田義博; 迫田義博, 日本野生動物医学会大会・講演要旨集, 30th, 2024
• Study of the administration route of baloxavir marboxil in non-clinical models-Aiming to improve absorption in the Okinawa rail-
  三木万梨子; 島津陽; 尾原涼; 大崎裕美; 宍戸貴雄; 池中良徳; 木村享史; 日尾野隆大; 日尾野隆大; 磯田典和; 磯田典和; 迫田義博; 迫田義博, 日本野生動物医学会大会・講演要旨集, 30th, 2024
• 環境毒性物質が鳥類の腸内細菌叢に与える影響
  小笠原浩平; 矢野琳太郎; 伊藤和顕; 森田鮎子; 小出将士; 徳長ゆり香; 眞下大和; 丸山瑞貴; 池中良徳; 中尾亮; 福間直希; 中山翔太; 石塚真由美, 日本獣医学会学術集会講演要旨集, 167th, 2024
• Influence of environmental toxicants on avian gut microbiome
  小笠原浩平; 矢野琳太郎; 伊藤和顕; 森田鮎子; 小出将士; 徳長ゆり香; 眞下大和; 丸山瑞貴; 池中良徳; 中尾亮; 福間直希; 中山翔太; 石塚真由美, Journal of Toxicological Sciences, 49, Supplement (CD-ROM), 2024
• 殺細胞効果を有する液体の膀胱内注入治療法の検討
  佐々木東; 池中良徳; 安井博宣; 中村健介; 滝口満喜, 日本獣医学会学術集会講演要旨集, 167th, 2024
• 鳥類におけるδ-アミノレブリン酸脱水酵素(ALAD)の鉛曝露に対する感受性種差の解明
  丸山瑞貴; 渡邊有希子; 石井千尋; 齊藤慶輔; 牛根奈々; 伊藤真輝; 銅谷理緒; 小笠原浩平; 池中良徳; 池中良徳; 池中良徳; ベイェネ ヤレド; 石塚真由美; 中山翔太; 中山翔太, 日本獣医学会学術集会講演要旨集, 167th, 2024
• Pharmacokinetic and Pharmacodynamic (PK/PD) Analysis to Assess Sensitivity of Wild Roof Rats (Rattus rattus) in the Bonin Islands to Rodenticide Diphacinone
  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
• 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, Dec. 2023
  日本野生動物医学会, Japanese
• Application of analytical chemistry methods for unraveling developmental toxicity and the mechanisms using zebrafish embryos
  久保田彰; REHAB Ahmed; XING Chen; SEUNG Lee Jae; 池本秀樹; 小椋響子; 田上瑠美; 野見山桂; 高橋真; 石橋弘志; 後藤哲智; 国末達也; 中村達朗; 村田幸久; 寺岡宏樹; 池中良徳, 環境化学討論会要旨集(CD-ROM), 31st, 2023
• Evaluation of Rodenticide Susceptibility of the Natural Monument; Bonin Flying Fox using AlphaFold2 and Molecular Simulation
  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
• 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
• 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
  亀谷牧子; 古川瑛理; 古川瑛理; 池中良徳; 松崎明; 柳川洋二郎; 片桐成二, 日本獣医学会学術集会講演要旨集, 166th, 2023
• Comparison of avian gut microbiota between grain- and fish-diet habit
  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
• Evolutionary history of UGT genes involved in xenobiotic metabolism in mammals and birds and their relationship to plants
  川合佑典; 池中良徳; 池中良徳; 生城真一; 西川美宇; 一色乃亜; 武田一貴; 中山翔太; 中山翔太; 久保田彰; 石塚真由美, 日本進化学会大会プログラム・講演要旨集(Web), 25th, 2023
• 胎子授乳期ネオニコチノイド系農薬曝露が海馬記憶と小脳運動学習機能に及ぼす継世代影響
  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
• 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, Oct. 2022
  (一社)日本DOHaD学会, Japanese
• 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; 山口健史; 池田敦子; 池田敦子; 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; 中村明枝; 今雅史; 藤谷倫子; 原田浩二; 岸玲子, DOHad研究(Web), 10, 2, 2022
• Antipsychotic drug haloperidol altered neurotransmitter levels in zebrafish larvae
  小椋響子; 田上瑠美; 久保田彰; 水原奈々; 池中良徳; 寺岡宏樹; 国末達也; 野見山桂, 環境化学討論会要旨集(CD-ROM), 30th, 2022
• Combined neurotoxic effects of multiple chemicals evaluated by common key events in AOP for neurotoxicity
  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
• 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
• 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
• 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
• Adverse outcome pathway (AOP)-based approach for assessing the combined neurotoxic effects of multiple pesticides
  HIRANO Tetsushi; IKENAKA Yoshinori; HOSHI Nobuhiko; TABUCHI Yoshiaki, Annual Meeting of the Japanese Society of Toxicology, 49.1, P-4E, 2022
  One of the challenges in the current risk assessment for chemicals is that conventional toxicity assessment systems for assessing individual chemicals cannot evaluate the risk of combined exposure to chemical mixtures. Based on the concept of adverse outcome pathway (AOP), common key events in toxic mechanisms could be used as indexes to assess the combined effects of multiple chemicals. At the last conference, we reported a novel neurotoxic mechanism in which a pyrethroid deltamethrin caused an imbalance in the proteolytic system via the activation of mitophagy and inhibition of proteasome activity. In this study, we examined the neurotoxic effects of multiple pesticides by evaluating these endpoints as key events. We exposed 10 pesticides to mouse neuroblastoma Neuro-2a cells and measured mitochondrial membrane potential and proteolytic activities. The combined effects of pesticides on cell viability were measured by wst-8 assay and analyzed by CompuSyn software. Our data showed that a pyrethroid pesticide, permethrin or deltamethrin, and a phenylpyrazole pesticide, fipronil, shared common key events, such as mitochondrial dysfunction and accumulation of p62, an autophagy substrate marker. Combined exposure to these pesticides induced a further decrease in cell viability compared to single exposure, which showed synergistic effects with a combination index < 1. These data constitute the first analysis of synergistic neurotoxicity caused by combined exposure to different pesticides relation to the common key events of AOP for neurotoxicity., The Japanese Society of Toxicology, Japanese
• 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, Sep. 2021
  環境ホルモン学会(日本内分泌撹乱化学物質学会), Japanese
• 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], Sep. 2021
  (公社)日本獣医学会, English
• 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, Apr. 2021
  (公社)日本超音波医学会, Japanese
• Development of a sensitive analytical method for neurotransmitters in the brain using Py-Tag derivatization and liquid chromatography-tandem mass spectrometry
  小椋響子; 田上瑠美; 池中良徳; 寺岡宏樹; 久保田彰; 国末達也; 野見山桂, 環境ホルモン学会研究発表会プログラム・要旨集, 23rd (Web), 2021
• Development and application of sensitive analysis for neurotransmitters and related substances in the brain tissue using Py-Tag derivatization.
  小椋響子; 田上瑠美; 池中良徳; 寺岡宏樹; 久保田彰; 国末達也; 野見山桂, 環境化学討論会要旨集(CD-ROM), 29th, 2021
• Analysis of variation of serum metabolites in cats by BDE209 long-term exposure test using Smart Metabolite Database
  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
• 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
• 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
• 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
• 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
• Stage-specific exposure and developmental neurotoxicity assessment of low-dose clothianidin during neuronal circuit formation
  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
• Effects of the neonicotinoid pesticide clothianidin on the immune system and gut microbiota in the next generation
  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
• Mechanism analyses of neurotoxicity of pyrethroid pesticide deltamethrin caused by the imbalance in proteolytic systems
  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
• 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
• 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
• 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
• Why wild birds in Japan still suffer from lead poisoning?
  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
• Toxicity assessment of the neonicotinoid insecticide clothianidin on frogs
  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
• Evolutionary analysis of UDP-glucuronosyltransferase genes in vertebrates using a genome database
  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
• Species differences in xenobiotics metabolism and detoxification-introduction-
  石塚真由美; 中山翔太; 池中良徳, Journal of Toxicological Sciences, 46, Supplement, 2021
• Evaluation of the effects of pesticides on the nervous system~Establishment and application of a highly sensitive analytical method for monoamine neurotransmitters~
  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
• Elucidation of the pathophysiology of hyperadrenocortical hyperfunction (Cushing’s syndrome) by simultaneous analysis of steroid hormones using LC-MS/MS
  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
• The disruption of brain function in mice administered with nicotinic acetylcholine receptor agonists~The development of the detection method using two-photon microscopy~
  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
• Evaluation of the ameliorative effect of Spirulina (Arthrospira platensis) supplementation on parameters relating to lead poisoning and obesity in C57BL/6J mice
  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
• Safety aspects of ultrasound-assisted intravesical chemotherapy in dogs
  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
• 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
• 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
• 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
• 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
• 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, 20 Aug. 2019
  Japanese
• 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), 07 Aug. 2019
  Japanese
• 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, Aug. 2019
  (公社)日本獣医学会, Japanese
• 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, Aug. 2019
  (公社)日本獣医学会, Japanese
• 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, Aug. 2019
  (公社)日本獣医学会, Japanese
• 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, 20 Jul. 2019
  (株)へるす出版, Japanese
• 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, 11 Jun. 2019
  Japanese
• 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, 11 Jun. 2019
  Japanese
• 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, 11 Jun. 2019
  Japanese
• 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, 11 Jun. 2019
  Japanese
• 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, 11 Jun. 2019
  Japanese
• 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, 11 Jun. 2019
  Japanese
• 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, 11 Jun. 2019
  Japanese
• 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, 11 Jun. 2019
  Japanese
• 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, Journal of Toxicological Sciences, 44, Suppl., S53, S53, Jun. 2019
  (一社)日本毒性学会, Japanese
• 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, 26 Mar. 2019
  Japanese
• Survey on exposure of neonicotinoid pesticide in wild mammals
  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
• 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
• Characterization and differentiation of xenobiotic metabolism in mammalian animals through glucuronidation and sulfation profiling
  SAENGTIENCHAI Aksorn; IKENAKA Yoshinori; NAKAYAMA Shouta M.M.; ISHIZUKA Mayumi, 環境化学討論会要旨集(CD-ROM), 28th, 2019
• Interactions of Neonicotinoid Insecticide with High Fat Diet Potentiate Signals of Type 2 Diabetogenesis in a Rodent Model.
  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
• In Vivo Pharmacokinetic/pharmacodynamic analysis of first-generation anticoagulant rodenticide warfarin with Egyptian fruit bats (Rousettus aegyptiacus) for risk assessment of Bonin fruit bats (Pteropus pselaphon)
  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
• 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
• 「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
• 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
• Exposure situation of neonicotinoids and its toxicity evaluation
  IKENAKA Yoshinori; TAIRA Kumiko; ARIZONO Kouji; HOSHI Nobuhiko; FUJIOKA Kazutoshi; ISHIZUKA Mayumi; ICHISE Takahiro; NIMAKO Collins; NAKAYAMA Shouta M.M.; HIRANO Tetsushi; ICHIKAWA Go; KATO Keisuke; TAKAHASHI Keisuke; HASEGAWA Hiroshi, Annual Meeting of the Japanese Society of Toxicology, 46, 0, S7, 2, 2019
  

  [in Japanese]

  , The Japanese Society of Toxicology, Japanese
• Concentration of neonicotinoid insecticides and their metabolites in Japanese bottled green-tea beverages and their safety evaluation
  Takamoto Akiko; Ishibashi Hiroshi; Ishizuka Mayumi; Arizono Koji; Ikenaka Yoshinori; Sugimoto Mayu; Iwano Manami; Fukushima Satoshi; Ichise Takahiro; Nakayama Shouta M. M.; Takahashi Keisuke; Kato Keisuke, Japanese Journal of Food Chemistry and Safety, 26, 1, 17, 27, 2019
  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., Japanese Society of Food Chemistry, English
• 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, Dec. 2018, [Peer-reviewed], [International Magazine]
  English
• 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, Dec. 2018, [Peer-reviewed], [International Magazine]
  English
• 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, Dec. 2018
  環境ホルモン学会(日本内分泌撹乱化学物質学会), Japanese
• 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, Dec. 2018
  Japanese
• Linking organochlorine exposure to biomarker response patterns in Anurans: a case study of Muller's clawed frog (Xenopus muelleri) from a tropical malaria vector control region
  Nico J. Wolmarans; Louis H. Du Preez; Yared Beyene Yohannes; Yoshinori Ikenaka; Mayumi Ishizuka; Nico J. Smit; Victor Wepener, ECOTOXICOLOGY, 27, 9, 1203, 1216, Nov. 2018, [Peer-reviewed], [International Magazine]
  English
• 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, 25 Sep. 2018
• 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, 14 Sep. 2018
  Japanese
• 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, Sep. 2018, [Peer-reviewed], [International Magazine]
  English
• 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, Sep. 2018
  Japanese, Summary national conference
• 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, 21 Aug. 2018
  Japanese
• 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, 21 Aug. 2018
  (公社)日本獣医学会, Japanese
• 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, 21 Aug. 2018
  Japanese
• 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, 21 Aug. 2018
  Japanese
• 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, 15 Aug. 2018
  Academic Press, English
• What Makes Super Rats "Super"? ~Investigation of Mechanisms of Rodenticide Resistance~
  TAKEDA Kazuki; IKENAKA Yoshinori; TANAKA Kazuyuki D; NAKAYAMA Shouta M.M; TANIKAWA Tsutomu; MIZUKAWA Hazuki; ISHIZUKA Mayumi, Annual Meeting of the Japanese Society of Toxicology, 45, 0, P, 71, 10 Aug. 2018
  <p>[in Japanese] </p>, The Japanese Society of Toxicology, Japanese
• Lead (Pb) pollution in Kabwe Mining area, Zambia: 10 years research achievements and future perspectives
  NAKAYAMA Shouta MM; ZYAMBO Golden; KURITANI Takeshi; NAKAGAWA Mitsuhiro; MIZUKAWA Hazuki; ISHIZUKA Mayumi; YABE John; IKENAKA Yoshinori; MUZANDU Kaampwe; CHOONGO Kennedy; NAKATA Hokuto; TOYOMAKI Haruya; BEYENE Yared; KATABA Andrew, Annual Meeting of the Japanese Society of Toxicology, 45, 0, P, 35, 10 Aug. 2018
  <p>[in Japanese] </p>, The Japanese Society of Toxicology
• Genetic and enzymatic features of phase II xenobiotic metabolism enzymes in carnivora species
  KONDO Takamitsu; IKENAKA Yoshinori; NAKAYAMA Shouta M. M; MIZUKAWA Hazuki; MITANI Yoko; NOMIYAMA Kei; TANABE Shinsuke; ISHIZUKA Mayumi, Annual Meeting of the Japanese Society of Toxicology, 45, 0, P, 60, 10 Aug. 2018
  <p>[in Japanese] </p>, The Japanese Society of Toxicology
• 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, Aug. 2018
  Japanese
• 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, Aug. 2018
  Japanese
• 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, Aug. 2018
  Japanese
• 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, Aug. 2018
  Japanese
• 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, Aug. 2018
  (公社)日本獣医学会, Japanese
• 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, Jun. 2018
  Japanese
• 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, Jun. 2018
  Japanese
• 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, Jun. 2018
  Japanese
• 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, 11 May 2018
  Japanese
• 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, 11 May 2018
  Japanese
• 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), 11 May 2018
  Japanese
• 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), 11 May 2018
  Japanese
• 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), 11 May 2018
  Japanese
• 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), 11 May 2018
  Japanese
• 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, 11 May 2018
  Japanese
• 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, 11 May 2018
  Japanese
• 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), 11 May 2018
  Japanese
• 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, 11 May 2018
  Japanese
• 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, 11 May 2018
  Japanese
• 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), 11 May 2018
  Japanese
• 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, 01 May 2018
  Springer New York LLC, English
• 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, 01 May 2018, [International Magazine]
  English
• 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, 26 Mar. 2018
  Japanese
• 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, [Peer-reviewed], [International Magazine]
  English
• 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
  Japanese
• 化学汚染の毒性影響の検知
  石塚真由美; 池中良徳; 中山翔太, 日本環境化学会講演会予稿集, 60th, 8, 2018
  Japanese
• Effects of PCB-exposure on thyroid hormone homeostasis in dog (canis lupus familiaris) and cat (felis catus)
  TAKAGUCHI Kohki; NAKAYAMA Shouta; IKENAKA Yoshinori; ISHIZUKA Mayumi; IWATA Hisato; KUNISUE Tatsuya; TANABE Shinsuke; NOMIYAMA Kei; NISHIKAWA Hiroyuki; MIZUKAWA Hazuki; TANOUE Rumi; KUSAKI Momoko; YOKOYAMA Nozomu; ICHII Osamu; TAKIGUCHI Mitsuyoshi, Annual Meeting of the Japanese Society of Toxicology, 45, 0, P, 72, 2018
  

  [in Japanese]

  , The Japanese Society of Toxicology, Japanese
• 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, Dec. 2017
  Japanese
• Chemical Hazard in Bird Species
  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, 22, 4, 69, 72, Dec. 2017
  日本野生動物医学会, Japanese
• 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, Dec. 2017
  Japanese
• 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, Dec. 2017
  環境ホルモン学会(日本内分泌撹乱化学物質学会), Japanese
• 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, 15 Sep. 2017
  Japanese
• 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, 15 Sep. 2017
  Japanese
• 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, 15 Sep. 2017
  Japanese
• 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, Sep. 2017, [Peer-reviewed], [International Magazine]
  English
• 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, Sep. 2017
  日本環境化学会, Japanese
• 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, 30 Aug. 2017
  Japanese
• 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, Aug. 2017
  (公社)日本獣医学会, Japanese
• 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, 05 Jun. 2017
  Japanese
• 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, 05 Jun. 2017
  Japanese
• 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, 05 Jun. 2017
  Japanese
• 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, 05 Jun. 2017
  Japanese
• 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, 05 Jun. 2017
  Japanese
• 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, 05 Jun. 2017
  Japanese
• 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, 05 Jun. 2017
  Japanese
• 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, 05 Jun. 2017
  Japanese
• 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, Jun. 2017
  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。, The Japanese Society of Toxicology, Japanese
• 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, Jun. 2017
  Japanese
• 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, 26 Mar. 2017
  Japanese
• 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
• Studies on polycyclic aromatic hydrocarbons formation in heat-treated meat
  DARWISH Wageh Sobhy; IKENAKA Yoshinori; NAKAYAMA Shouta M.M; MIZUKAWA Hazuki; ISHIZUKA Mayumi, Annual Meeting of the Japanese Society of Toxicology, 44, 0, O, 15, 2017
  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., The Japanese Society of Toxicology, Japanese
• Thyroid hormone effects of polychlorinated biphenyls (PCBs) in cats-Analysis of deiodination and metabolism-
  MIZUKAWA Hazuki; NAKAYAMA Shouta M.M.; SAINNOXOI Tsend-ayush; TANABE Shinsuke; ISHIZUKA Mayumi; TAKAI Nana; YOKOYAMA Nozomu; ICHII Osamu; TAKIGUCHI Mitsuyoshi; NOMIYAMA Kei; TAKAGUCHI Kohki; NISHIKAWA Hiroyuki; IKENAKA Yoshinori, Annual Meeting of the Japanese Society of Toxicology, 44, 0, P, 55, 2017
  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。, The Japanese Society of Toxicology, Japanese
• Estimation of the exposure level of neonicotinoid pesticide for infant
  IKENAKA Yoshinori; KATO Keisuke; TOHYAMA Chiharu; ISHIZUKA Mayumi; MIYABARA Yuichi; ICHISE Takahiro; YAGIHASHI Mio; NAKAYAMA Shouta; MIZUKAWA Hazuki; TAIRA Kumiko; ARIZONO Koji; TAKAHASHI Keisuke, Annual Meeting of the Japanese Society of Toxicology, 44, 0, O, 20, 2017
  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
• Analysis of lead in wild birds to identify the cause of lead-poisoning
  石井千尋; 中山翔太; 水川葉月; 池中良徳; 石塚真由美, 中毒研究, 30, 4, 363, 367, 2017
  日本中毒学会 ; 2009-, Japanese
• Thyroid hormone effects of polychlorinated biphenyls (PCBs) in cats-Analysis of deiodination and metabolism-
  MIZUKAWA Hazuki; NAKAYAMA Shouta M.M.; SAINNOXOI Tsend-ayush; TANABE Shinsuke; ISHIZUKA Mayumi; TAKAI Nana; YOKOYAMA Nozomu; ICHII Osamu; TAKIGUCHI Mitsuyoshi; NOMIYAMA Kei; TAKAGUCHI Kohki; NISHIKAWA Hiroyuki; IKENAKA Yoshinori, Annual Meeting of the Japanese Society of Toxicology, 44, 0, P, 55, 2017
  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、<i>in vivo</i>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。<br>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。, The Japanese Society of Toxicology, Japanese
• 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
  Japanese
• 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
  Japanese
• 薬物代謝酵素の動物種差
  石塚真由美; 中山翔太; 水川葉月; 池中良徳, 日本薬学会年会要旨集(CD-ROM), 137th, ROMBUNNO.S45‐4, 2017
  Japanese
• 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
  Japanese
• 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
  English
• 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, Jan. 2017
  English
• Characterization of Species Differences in Xenobiotic Metabolism in Non-experimental Animals
  Mizukawa Hazuki; Ikenaka Yoshinori; Kakehi Mayu; Nakayama Shouta; Ishizuka Mayumi, YAKUGAKU ZASSHI, 137, 3, 257, 263, 2017
  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.
  , The Pharmaceutical Society of Japan, Japanese
• 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, Dec. 2016
  環境ホルモン学会(日本内分泌撹乱化学物質学会), Japanese
• 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, 10 Nov. 2016
  Japanese
• Novel revelation of warfarin resistant mechanism in roof rats (Rattus rattus) using pharmacokinetic/pharmacodynamic analysis.
  Kazuki Takeda; Yoshinori Ikenaka; Tsutomu Tanikawa; Kazuyuki D Tanaka; Shouta M M Nakayama; Hazuki Mizukawa; Mayumi Ishizuka, Pesticide biochemistry and physiology, 134, 1, 7, Nov. 2016, [Peer-reviewed], [International Magazine]
  English
• 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, Oct. 2016
  English
• 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, 23 Sep. 2016
  Japanese
• ネオニコチノイド系農薬の生体への曝露実態
  池中良徳, Endocrine Disrupter News Letter, 19, 2, 5, Sep. 2016
  Japanese
• 野生動物の化学物質蓄積や感受性の種差
  石塚真由美; 中山翔太; 水川葉月; 池中良徳, 日本獣医学会学術集会講演要旨集, 159th, 293, 30 Aug. 2016
  Japanese
• 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, 30 Aug. 2016
  Japanese
• 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, 30 Aug. 2016
  Japanese
• 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, 30 Aug. 2016
  Japanese
• 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, 30 Aug. 2016
  Japanese
• 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, 06 Jun. 2016
  Japanese
• 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, 06 Jun. 2016
  Japanese
• 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, 06 Jun. 2016
  Japanese
• 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, 06 Jun. 2016
  Japanese
• 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, 06 Jun. 2016
  Japanese
• 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, 06 Jun. 2016
  Japanese
• 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, Jun. 2016
  Japanese
• 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, Jun. 2016
  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。, The Japanese Society of Toxicology, Japanese
• 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, Jun. 2016
  Japanese
• 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, Jun. 2016
  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。, The Japanese Society of Toxicology, Japanese
• 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, Mar. 2016, [Peer-reviewed]
  English
• 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
  Japanese
• 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
  Japanese
• 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
  Japanese
• In vivo analysis of metabolic capacities and effects on the thyroid hormone and in cats treated with polychlorinated biphenyls
  MIZUKAWA Hazuki; TAKAGUCHI Kohki; TANABE Shinsuke; ISHIZUKA Mayumi; MAEHARA Misaki; YOKOYAMA Nozomu; ICHII Osamu; TAKIGUCHI Mitsuyoshi; NOMIYAMA Kei; NISHIKAWA Hiroyuki; IKENAKA Yoshinori; NAKAYAMA Shouta M.M., Annual Meeting of the Japanese Society of Toxicology, 43, 0, P, 6, 2016
  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。, The Japanese Society of Toxicology, Japanese
• Elucidation of neonicotinoids exposure to human: Determination of urinary neonicotinoid pesticides and its metabolites
  IKENAKA Yoshinori; ISHIZUKA Mayumi, Annual Meeting of the Japanese Society of Toxicology, 43, 0, W3, 3, 2016
  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。, The Japanese Society of Toxicology, Japanese
• Investigation of pharmacokinetics / pharmacodynamics status in a closed colony of warfarin resistant rats (Rattus rattus) from Tokyo
  TAKEDA Kazuki; IKENAKA Yoshinori; TANAKA Kazuyuki D; TANIKAWA Tsutomu; NAKAYAMA Shouta M.M; MIZUKAWA Hazuki; ISHIZUKA Mayumi, Annual Meeting of the Japanese Society of Toxicology, 43, 0, P, 89, 2016
  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。, The Japanese Society of Toxicology, Japanese
• Species differences in UGT-dependent metabolisms
  ISHIZUKA Mayumi; NAKAYAMA Shouta; MIZUKAWA Hazuki; IKENAKA Yoshinori, Annual Meeting of the Japanese Society of Toxicology, 43, 0, S16, 4, 2016
  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。, The Japanese Society of Toxicology, Japanese
• Elucidation of the function of Aryl hydrocarbon reseptor (AhR) at adipose tissue
  MOTOHIRA Kodai S; IKENAKA Yoshinori; DARWISH Wageh S; NAKAYAMA Shouta M.M; MIZUKAWA Hazuki; ISHIZUKA Mayumi, Annual Meeting of the Japanese Society of Toxicology, 43, 0, P, 84, 2016
  【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。, The Japanese Society of Toxicology, Japanese
• In vivo analysis of metabolic capacities and effects on the thyroid hormone and in cats treated with polychlorinated biphenyls
  MIZUKAWA Hazuki; TAKAGUCHI Kohki; TANABE Shinsuke; ISHIZUKA Mayumi; MAEHARA Misaki; YOKOYAMA Nozomu; ICHII Osamu; TAKIGUCHI Mitsuyoshi; NOMIYAMA Kei; NISHIKAWA Hiroyuki; IKENAKA Yoshinori; NAKAYAMA Shouta M.M., Annual Meeting of the Japanese Society of Toxicology, 43, 0, P, 6, 2016
  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 <i>in vivo</i>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。<br>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<i>in vivo</i>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、<i>CYP1A1</i>および<i>CYP1A2</i>遺伝子の発現量の上昇も認められた。<br> 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。, The Japanese Society of Toxicology, Japanese
• Is hedgehog high sensitive to xenobiotics? Low metabolism enzyme activities observed in African hedgehog (Atalerix albiventris)
  SAENGTIENCHAI Aksorn; IKENAKA Yoshinori; SAM Nesta Bortey; JERMNARK Usuma; MIZUKAWA Hazuki; NAKAYAMA Shouta M.M; ISHIZUKA Mayumi, Annual Meeting of the Japanese Society of Toxicology, 43, 0, P, 237, 2016
  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, Japanese
• ネオニコチノイド系農薬の生体への曝露実態
  池中良徳, 日本内分泌かく乱化学物質学会講演会テキスト, 30th, 21‐30, 2016
  Japanese
• 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, 30 Aug. 2015
  Japanese
• 鳥類で起こっているケミカルハザードとそのメカニズム
  中山翔太; 水川葉月; 池中良徳; 石塚真由美, 日本野生動物医学会大会・講演要旨集, 21st, 22, 01 Jul. 2015
  Japanese
• 殺鼠剤抵抗性ネズミはどのようにして抵抗性を獲得したのか?~化学物質の感受性の種差と系統差~
  池中良徳, 衛生動物, 66, 2, 48, 25 Jun. 2015
  Japanese
• 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, 17 Jun. 2015
  Japanese
• 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, 17 Jun. 2015
  Japanese
• 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, 17 Jun. 2015
  Japanese
• 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, 17 Jun. 2015
  Japanese
• 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, 17 Jun. 2015
  Japanese
• 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, 17 Jun. 2015
  Japanese
• 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, Jun. 2015
  【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。, The Japanese Society of Toxicology, Japanese
• 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, Jun. 2015
  Japanese
• 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, Apr. 2015
  English
• 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, 27 Mar. 2015
  Japanese
• 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), 05 Mar. 2015
  Japanese
• 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, Annual Meeting of the Japanese Society of Toxicology, 42, 0, O, 20, 2015
  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., The Japanese Society of Toxicology, Japanese
• Drug metabolism Phase II enzymes -The novel way of identification of species differences-
  IKENAKA Yoshinori; SAENGTIENCHAI Aksorn; KAKEHI Mayu; DARWISH Wageh Sobhy; MIZUKAWA Hazuki; NAKAYAMA Shouta M.M; ISHIZUKA Mayumi, Annual Meeting of the Japanese Society of Toxicology, 42, 0, S9, 3, 2015
  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。, The Japanese Society of Toxicology, Japanese
• Functional analysis of xenobiotic glucuronidation of cynomolgus monkey UDP-glucuronosyltransferase (UGT) using budding yeast expression system
  TAKAHIRA Rika; UNO Yasuhiro; IKENAKA Yoshinori; ISHIZUKA Mayumi; NISHIKAWA Miyu; SAKAKI Toshiyuki; IKUSHIRO Shinichi, Annual Meeting of the Japanese Society of Toxicology, 42, 0, O, 25, 2015
  【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。, The Japanese Society of Toxicology, Japanese
• 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, 01 Jan. 2015
• 外来化学物質の代謝の種差
  石塚真由美; 中山翔太; 水川葉月; 池中良徳, 日本毒性病理学会講演要旨集, 31st, (JA)44,(EN)116, 2015
  Japanese
• 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, 15 Oct. 2014
  Japanese
• 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, 17 Sep. 2014
  Japanese
• 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, 11 Aug. 2014
  Japanese
• 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, 11 Aug. 2014
  Japanese
• 鉛弾規制後も生じているワシ類における鉛汚染の実態
  渡辺有希子; 角田真穂; 石井千尋; 池中良徳; 石塚真由美; 齊藤慶輔, 北海道獣医師会雑誌, 58, 8, 389, 10 Aug. 2014
  Japanese
• 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, Jul. 2014
  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, Japanese
• 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, Jul. 2014
  【はじめに】北海道では、猛禽類において鉛弾摂取による鉛中毒が問題となっている。現在は鉛弾の使用規制が設けられているものの、未だに被害個体が発見されている。また、本州など他地域でも鉛中毒個体が発見されているが、北海道を除く地域における汚染実態調査は極僅かであり、鉛弾使用規制も不十分である。そこで、本研究では北海道、本州、四国において死亡した猛禽類の鉛濃度と鉛安定同位体比を測定し、鉛汚染状況と汚染源の解明を試みた。<br>【方法】試料は、1993年から2014年に北海道、本州、四国で死亡したイヌワシ、トビ、オオワシ、オオタカ、フクロウ、オジロワシ、オオハヤブサ、クマタカ、サシバ、ハイタカ、ツミ、チョウゲンボウの計49個体の肝臓を採取し、誘導結合プラズマ質量分析計で鉛濃度と鉛安定同位体比（²⁰⁷Pb/²⁰⁶Pb、²⁰⁸Pb/²⁰⁶Pb）を分析した。<br>【結果と考察】本研究の結果、1999‐2014年に北海道で死亡した4羽のオオワシにおいて、鉛中毒が疑われる値（11.0-29.5 mg/kg、湿重量）が検出された。北海道では2004年に大型獣の狩猟における鉛弾使用が禁止されているが、2013、2014年に採取されたオオワシにおいても高濃度の鉛蓄積が検出され、このうち1羽からはレントゲン撮影と剖検で胃内に鉛弾の破片が認められた。また岩手県で死亡したイヌワシからも高濃度の鉛蓄積（2.0 mg/kg）が認められた。さらに鉛安定同位体比を分析した結果、高濃度の鉛蓄積個体の鉛安定同位体比の値が同程度であった。このうち1羽から鉛弾が検出されたことを考慮すると、これらの高濃度蓄積個体の汚染源は鉛ライフル弾であると考えられた。<br> 上記の結果から、猛禽類の鉛弾摂取による中毒が未だに問題となっていることが明らかとなった。従って、北海道以外の地域における調査、また日本全国における鉛弾流通の完全禁止など規制強化の検討が必要であると考えられた。, 日本毒性学会, Japanese
• 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, Jul. 2014
  【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, Japanese
• 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, Jul. 2014
  【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, Japanese
• 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, 14 May 2014
  Japanese
• 諏訪湖における底質中の重金属類濃度の変遷
  吉田知可; 池中良徳; 宮原裕一, 環境化学討論会要旨集(CD-ROM), 23rd, ROMBUNNO.P-179, 14 May 2014
  Japanese
• 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, 14 May 2014
  Japanese
• 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, 14 May 2014
  Japanese
• 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, 14 May 2014
  Japanese
• 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
  Japanese
• 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
  Japanese
• 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
  Japanese
• 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, 13 Sep. 2013
  Japanese
• 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, 30 Aug. 2013
  Japanese
• カニクイザルUGT1Aの同定・解析
  宇野泰広; 池中良徳; 石塚真由美, 日本獣医学会学術集会講演要旨集, 156th, 388, 30 Aug. 2013
  Japanese
• 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, Jul. 2013
  English
• 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, Jul. 2013
  Japanese
• 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, Jul. 2013
  Japanese
• 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, Jul. 2013
  Japanese
• 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, Apr. 2013
  文永堂出版(株), Japanese
• 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, 05 Mar. 2013
  Japanese
• ワルファリンの抵抗性メカニズム
  池中良徳, 日本獣医学会学術集会講演要旨集, 155th, 166, 04 Mar. 2013
  Japanese
• 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, 04 Mar. 2013
  Japanese
• 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, Annual Meeting of the Japanese Society of Toxicology, 40, 0, 2013
  Introduction : Reptile populations all around the world are decreasing. The dominant stressors are decrease of habitats, targeted harvesting and climate change. Environmental pollution could be a common factor weakening populations, yet we know little about the effect of xenobiotics on reptiles. Pyrene, as a representative of polycyclic aromatic hydrocarbons (PAHs), was choosen to study the metabolism in freshwater turtles, as disasters involving PAHs (oil spills) are one of the main causes of health and reproductive problems in water-living organism. <br>Materials and Methods:Red-eared sliders (<i>Trachemys scripta elegans</i>), Chinese pond turtles (<i>Mauremys reevesii</i>) and Chinese softshell turtles (<i>Pelodiscus sinensis</i>) were used. Pyrene exposure occurred thorugh oral feeding (4 mg/kg pyrene, dissolved in corn oil) or through water (250 &mu;g/l). Exposed water was filtered, passed through a solid-phase cartridge, and eluded with methanol. Metabolites were determined by HPLC with FD equipped with an ODS column, and identified by an MS/MS system. Liver subcellular fractions were isolated from fresh samples, protein concentration were measured by BCA protein assay. EROD, UGT and SULT activity were measured.<br>Results and Discussion:Distinct metabolite distributions were measured for each species. The dominant metabolite in all three species was pyrene-1-sulfate. All enzyme activities were low compared to mammals (rat). Sulfate conjugation was the dominant phase II metabolic pathway in all three species., The Japanese Society of Toxicology, English
• Regulatory effects of carotenoids on Aryl hydrocarbon receptor (AhR) gene battery
  DARWISH Wageh Sobhy; IKENAKA Yoshinori; NAKAYAMA Shouta; ISHIZUKA Mayumi, Annual Meeting of the Japanese Society of Toxicology, 40, 0, 2013
  <b>[Introduction]</b> <br> In our previous work, positive correlations between CYP1A- dependent activities, protein expression and &beta;-carotene (BC) accumulation in the ungulates were observed, however these cross-talks were poorly understood. Additionally, the regulatory effects of carotenoids on xenobiotics metabolizing enzymes (XMEs) had received little attention. Thus, the aim of the current study is to deeply investigate the constitutive response of AhR gene battery to the exposure to BC under various doses in the human hepatoma cell line (HEPG2) cells. Moreover, the possible regulatory mechanisms of these cross-talks between AhR and BC will be declared.<br> <b>[Materials and Methods]</b> <br> HEPG2 cell lines were treated with different concentrations of BC (0-10 &micro;M) for 12-24h. The mRNA expression for phase I (CYP1A1 and 1A2), Phase II (UGT1A6 and NQO1) enzymes and AhR were examined using Real-Time PCR. Protein expression of AhR was investigated using western blotting. Rat H4IIE cells were transfected with h-XRE luciferase reporter plasmid and exposed to BC for 24h and dual- luciferase reporter assay was performed.<br> <b>[Results and Discussion]</b> <br> BC differentially modulated XMEs (Phase I and II enzymes) expression in dose-dependent fashion. In parallel, BC induced AhR mRNA, protein expression and luciferase activity. Thus, &beta;-carotene differentially modulated AhR gene battery., The Japanese Society of Toxicology, English
• 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, 31 Aug. 2012
  Japanese
• 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, 10 Jul. 2012
  English
• 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, 10 Jul. 2012
  English
• 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, 10 Jul. 2012
  Japanese
• 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, 10 Jul. 2012
  Japanese
• Xenobiotics metabolism in avian species: Characterization of Phase I and Phase II metabolism and species differences
  IKENAKA YOSHINORI; KAWATA MINAMI; WATANABE KENSUKE; SAENGTIENCHAI AKSORN; ONO MARUMI; ISHIZUKA MAYUMI, 環境化学討論会要旨集(CD−ROM), 21st, ROMBUNNO.P-211, 10 Jul. 2012
  Japanese
• 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, 10 Jul. 2012
  Japanese
• 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, Jul. 2012
  【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, Japanese
• 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, 25 Jun. 2012
  Japanese
• 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, Jun. 2012
  English
• 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, Apr. 2012
  English
• 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, 31 Mar. 2012
  Japanese
• 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, 01 Mar. 2012
  Japanese
• 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, Feb. 2012
  English
• 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
• 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, Jan. 2012
  English
• Comparative metabolism of warfarin in rats and chickens
  A. Saengtienchai; Y. Ikenaka; K. Watanabe; T. Ishida; M. Ishizuka, POULTRY SCIENCE, 90, 12, 2775, 2781, Dec. 2011
  English
• 汚染環境下の野生動物の適応と毒性
  石塚真由美; 池中良徳, 衛生薬学・環境トキシコロジー講演要旨集, 2011, 104, 05 Oct. 2011
  Japanese
• 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, 13 Sep. 2011
  Japanese
• 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, 13 Sep. 2011
  Japanese
• 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, 31 Aug. 2011
  Japanese
• 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, 31 Aug. 2011
  Japanese
• 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, Aug. 2011
  (公社)北海道獣医師会, Japanese
• 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; 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, Aug. 2011
  (公社)日本獣医学会, Japanese
• 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, 01 Jul. 2011
  English
• 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, 01 Jul. 2011
  English
• 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, 01 Jul. 2011
  Japanese
• 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, Jun. 2011
  English
• 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, Jun. 2011
  Japanese
• Sensitivity to Xenobiotics in Wildlife and Their Defense System Against Environmental Pollution
  IKENAKA Yoshinori; ISHIZUKA Mayumi, Journal of Japan Society for Safety Engineering, 50, 2, 80, 84, 15 Apr. 2011
  <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, Japanese
• 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, 01 Mar. 2011
  Japanese
• 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, 01 Mar. 2011
  Japanese
• 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, 31 Jan. 2011
  Japanese
• 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, Dec. 2010
  English
• 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, Nov. 2010
  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, English
• アフリカ諸国における重金属汚染の現状と野生動物への影響
  池中良徳; 中山翔太; 石塚真由美, 北海道獣医師会雑誌, 54, 10, 569, 575, 10 Oct. 2010
  Japanese
• 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, 01 Sep. 2010
  Japanese
• 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, 01 Sep. 2010
  Japanese
• 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, 01 Sep. 2010
  Japanese
• 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, 10 Aug. 2010
  Japanese
• 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, 10 Aug. 2010
  Japanese
• 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, Aug. 2010
  English
• 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, 20 Jun. 2010
  English
• 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, 20 Jun. 2010
  Japanese
• 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, 20 Jun. 2010
  Japanese
• 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, May 2010
  Japanese
• 鳥類におけるワルファリン感受性の比較
  渡邉研右; 田中和之; 池中良徳; 石塚真由美, J Toxicol Sci, 35, Supplement, S231, May 2010
  Japanese
• 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, May 2010
  Japanese
• 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
  Japanese
• Warfarin-resistant of rats in Japan
  TANAKA Kazuyuki; HARUNARI Tsunehito; TANIKAWA Tsutomu; IKENAKA Yoshinori; ISHIZUKA Mayumi, Japanese Journal of Environmental Toxicology, 12, 2, 61, 70, 30 Dec. 2009
  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, Japanese
• 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, 09 Jun. 2009
  English
• 鳥類ビタミンKエポキシド還元酵素のワルファリン感受性
  渡邉研右; 田中和之; 池中良徳; 藤田正一; 石塚真由美, 日本獣医学会学術集会講演要旨集, 148th, 293, 2009
  Japanese
• 舌に発現する薬物代謝酵素群と変異原物質の代謝機構
  滝口真美; SOBHY Wageh; 池中良徳; 藤田正一; 石塚真由美, 日本獣医学会学術集会講演要旨集, 148th, 293, 2009
  Japanese
• Characteristics of Accumulation Patterns of Polycyclic Aromatic Hydrocarbons in the Organisms Inhabited in Lake Suwa
  IKENAKA Yoshinori; ITO Yuuki; EUN Heesoo; WATANABE Eiki; MIYABARA Yuichi, Journal of environmental chemistry, 18, 3, 341, 352, 24 Sep. 2008
  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, Japanese
• Antibiotic furazolidone induces CYP1A but not CYP2E1 subfamily in rat liver
  Nobuo Sasaki; Noriaki Sakai; Yoshinori Ikenaka; Tomomi Kamiya; Min Heewon; Kentaro Q. Sakamotoo; Mayumi Ishizuka; Shoichi Fujita, JOURNAL OF VETERINARY MEDICAL SCIENCE, 70, 3, 223, 226, Mar. 2008
  English
• Characteristics of Accumulation Patterns of Polycyclic Aromatic Hydrocarbons in the Organisms Inhabited in Lake Suwa
  IKENAKA Yoshinori; ITO Yuuki; EUN Heesoo; WATANABE Eiki; MIYABARA Yuichi, Journal of Environmental Chemistry, 18, 3, 341, 352, 2008
  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, Japanese
• Estimation of the Annual Flux of Polycyclic Aromatic Hydrocarbons in Lake Suwa
  MIYABARA Yuichi; IKENAKA Yoshinori, Journal of environmental chemistry, 17, 4, 649, 658, 25 Dec. 2007
  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., 日本環境化学会, Japanese
• The characteristic of polycyclic aromatic hydrocarbons pollution in eutrophic lake "Lake Suwa" and relations with its catchment area
  池中良徳; 館野覚俊; 宮原裕一, Journal of environmental chemistry, 17, 2, 217, 226, 28 Jun. 2007
  日本環境化学会, Japanese
• 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, 19 Jun. 2007
  Japanese
• 諏訪湖水草帯における水質の不均一性
  宮原裕一; 犬塚良平; 池中良徳, 信州大学環境科学年報(Web), 29, WEB ONLY 24-28, Mar. 2007
  Japanese
• Estimation of the Annual Flux of Polycyclic Aromatic Hydrocarbons in Lake Suwa
  MIYABARA Yuichi; IKENAKA Yoshinori, Journal of Environmental Chemistry, 17, 4, 649, 658, 2007
  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, Japanese
• The Characteristic of Polycyclic Aromatic Hydrocarbons Pollution in Eutrophic Lake "Lake Suwa" and Relations with its Catchment Area
  IKENAKA Yoshinori; TATENO Akitoshi; MIYABARA Yuichi, Journal of Environmental Chemistry, 17, 2, 217, 226, 2007
  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, Japanese
• 7月豪雨の諏訪湖水質への影響
  宮原裕一; 池中良徳; 犬塚良平; 館野覚俊; 内山隆文, 日本陸水学会甲信越支部会報, 32, 72, Dec. 2006
  Japanese
• 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, 05 Sep. 2006
  日本陸水学会, Japanese
• 諏訪湖に生息する生物の多環芳香族炭化水素汚染
  池中良徳; 伊藤有希; 宮原裕一, 環境化学討論会講演要旨集, 15th, 100, 101, 19 Jun. 2006
  Japanese
• 諏訪湖におけるトリブチルスズの動態研究
  武田隼一; 池中良徳; 宮原裕一, 環境化学討論会講演要旨集, 15th, 646, 647, 19 Jun. 2006
  Japanese
• 多環芳香族炭化水素類の水圏における環境動態を決定する因子の解析
  館野覚俊; 池中良徳; 宮原裕一, 環境化学討論会講演要旨集, 15th, 96, 97, 19 Jun. 2006
  Japanese
• 諏訪湖における栄養塩濃度の変動に関する研究
  宮原裕一; 池中良徳; 犬塚良平; 花里孝幸, 信州大学環境科学年報, 28, 39, 46, 31 Mar. 2006
  Japanese
• 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
  日本陸水学会, Japanese
• 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, Dec. 2005
  Japanese
• 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, Nov. 2005
  English
• Microcystisの捕食者がmicrocystin生産に与える影響
  中村剛也; 池中良徳; 宮原裕一; 朴虎東, 日本陸水学会大会講演要旨集, 70th, 114, 10 Sep. 2005
  Japanese
• 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, 15 Jun. 2005
  Japanese
• 諏訪湖における多環芳香族炭化水素類の収支に関する研究
  宮原裕一; 池中良徳, 環境化学討論会講演要旨集, 14th, 698, 699, 15 Jun. 2005
  Japanese
• Depositional process of organic pollutants deduced from the sediment features in Lake Suwa, central Japan
  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, 06 Dec. 2004
  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 flood sediments 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. The annual changes of the persistent organic pollutants amount in the normal sediments well correspond with the history of human activities around the lake. Chemical and other analyses must be based sedimentary unit identified by lithology and density., 地質汚染－医療地質－社会地質学会, Japanese
• 長野県における野生生物中の多環芳香族炭化水素類について
  齊藤玲子; 池中良徳; 宮原裕一, 日本陸水学会甲信越支部会報, 30, 10, Nov. 2004
  Japanese
• 湖沼生物を介した多環芳香族炭化水素類の環境動態の解明―PyreneのDaphnia magnaによる代謝―
  池中良徳; 宮原裕一, 日本陸水学会甲信越支部会報, 30, 43, Nov. 2004
  Japanese
• 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, 05 Jul. 2004
  Japanese
• 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, 02 Dec. 2003
  Japanese
• 諏訪湖柱状堆積物から見たダイオキシン類発生域の推定
  池中良徳; 渡邊栄喜; 殷煕洙; 宮原裕一, 日本陸水学会甲信越支部会報, 29, 62, Dec. 2003
  Japanese
• 諏訪地域における多環芳香族炭化水素の発生域の推定
  上沢春香; 池中良徳; 宮原裕一, 日本陸水学会甲信越支部会報, 29, 32, Dec. 2003
  Japanese
• 諏訪湖及び諏訪湖集水域におけるダイオキシン類の異性体組成について
  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, 12th, 92, 93, 25 Jun. 2003
  Japanese

• 研究機器演習, 2024年, 博士後期課程, 国際感染症学院
• 大学院共通授業科目（一般科目）：自然科学・応用科学, 2024年, 修士課程, 大学院共通科目
• 研究機器演習, 2024年, 博士後期課程, 獣医学院
• 大学院共通授業科目（一般科目）：自然科学・応用科学, 2024年, 修士課程, 大学院共通科目
• 生物統計学特論, 2024年, 博士後期課程, 獣医学院
• 生物統計学特論, 2024年, 博士後期課程, 国際感染症学院
• Human-Animal Bond and One Health 特別科目群, 2024年, 博士後期課程, 獣医学院
• Human-Animal Bond and One Health 特別科目群, 2024年, 博士後期課程, 国際感染症学院
• 環境毒性学演習, 2024年, 博士後期課程, 獣医学院
• ケミカルハザード対策専門特論, 2024年, 博士後期課程, 獣医学院
• 保全医学演習, 2024年, 博士後期課程, 獣医学院
• 保全医学演習, 2024年, 博士後期課程, 国際感染症学院
• 環境獣医科学特論, 2024年, 博士後期課程, 獣医学院
• 環境と人間, 2024年, 学士課程, 全学教育
• HSI extension/professional program, 2024年, 学士課程, HSI
• アドバンスト演習, 2024年, 学士課程, 獣医学部
• アドバンスト演習, 2024年, 学士課程, 獣医学部
• アドバンスト演習, 2024年, 学士課程, 獣医学部
• 応用毒性学, 2024年, 学士課程, 獣医学部
• 毒性学実習, 2024年, 学士課程, 獣医学部
• 基礎動物栄養学, 2024年, 学士課程, 獣医学部

• Epigenomic Modifications and Health Implications of Plastic Additives: A Comprehensive Human and Cell Study
  Grants-in-Aid for Scientific Research
  01 Apr. 2025 - 31 Mar. 2029
  池田 敦子; 曾 怡; 小島 弘幸; 池中 良徳; KETEMA RAHEL・MESFIN; MEGASARI MARSELA; 山口 健史; アイツバマイ ゆふ
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, 25H01075
• Evaluation of the transgenerational effects of pesticides and epigenenomic toxicity from the perspective of paternal exposure effects
  Grants-in-Aid for Scientific Research
  01 Apr. 2025 - 31 Mar. 2028
  星 信彦; 池中 良徳; 平野 哲史; 横山 俊史
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Kobe University, 25K03271
• Search for novel, unregulated PPCPs with fish developmental and CNS toxicity
  Grants-in-Aid for Scientific Research
  01 Apr. 2024 - 31 Mar. 2028
  野見山 桂; 岩田 久人; 池中 良徳; 久保田 彰; 田上 瑠美; 江口 哲史
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Ehime University, 24H00779
• Creation of a platform for the evaluation of signal toxicity, starting with the development of methods for the detection and diagnosis of brain function disruption.
  Grants-in-Aid for Scientific Research
  01 Apr. 2023 - 31 Mar. 2027
  池中 良徳
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, 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
  28 Jun. 2024 - 31 Mar. 2026
  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))
  07 Oct. 2022 - 31 Mar. 2026
  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
• Adaptive evolution/change in mammals to exogenous chemicals (xenobiotics)
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
  05 Apr. 2021 - 31 Mar. 2026
  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。
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, 21H04919
• Elucidation of mechanisms of transgenerational effects of developmental neurotoxicity - Developmental program and epigenomic toxicity of pesticides
  Grants-in-Aid for Scientific Research
  01 Apr. 2024 - 31 Mar. 2025
  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）．
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Kobe University, 23K25004
• Construction and practice of MITA system for more sensitive and efficient toxicity testing
  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Pioneering)
  30 Jun. 2022 - 31 Mar. 2025
  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。
  Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Pioneering), Hokkaido University, 22K18425
• Elucidation of mechanisms of generational toxicology of developmental neurotoxicity - Developmental program and epigenomic toxicity of pesticides
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
  01 Apr. 2022 - 31 Mar. 2025
  星 信彦; 横山 俊史; 池中 良徳; 平野 哲史
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Kobe University, 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)
  01 Apr. 2022 - 31 Mar. 2025
  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
• Adverse health effects of environmental chemical exposure: elucidation of mechanisms via human and animal studies
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
  05 Apr. 2021 - 31 Mar. 2025
  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。
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, 21H04843
• Developmental neurotoxicity of pesticides based on the transgenerational inheritance and localized neural progenitor and glial cells activity
  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Exploratory)
  09 Jul. 2021 - 31 Mar. 2024
  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
  Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Exploratory), Kobe University, 21K19846
• Development of risk assessment method and present of brain transfer by ionic environmental contaminants using fish as an indicator
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
  01 Apr. 2020 - 31 Mar. 2024
  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。
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Ehime University, 20H00645
• Interaction of adrenal glands and liver in canine hepatocellular carcinoma
  Grants-in-Aid for Scientific Research
  01 Apr. 2020 - 31 Mar. 2023
  Takiguchi Mitsuyoshi
  Hepatocellular carcinoma (HCC) is a common primary liver tumor in dogs. Hyperadrenocorticism (HAC) was a highly concurrent disease with canine HCC. The aim was to specify the relationship between HCC and HAC in dogs. A total of 19 steroids were quantitatively measured using a developed liquid chromatography coupled with tandem mass spectrometry. In addition, DNA methylation levels were compared among liver tumor, surrounding region, and normal liver.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 20H03139
• Development and practice of "adaptive risk assessment based on biological monitoring" of insecticide
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
  01 Apr. 2019 - 31 Mar. 2022
  HOSHI NOBUHIKO
  Since developmental neurotoxicity is not included in the mandatory safety assessment of pesticides, it has been questioned whether the nontoxic amount (NOAEL) specified in the current law and the acceptable daily intake calculated from the NOAEL are really the values to ensure our health. In this study, we conducted a trans-omics analysis of exposure of mammalian animals to systemic pesticides (neonicotinoids and fipronil), which are currently the mainstay of pesticides, below the NOAEL. The results showed that the pesticides had effects on higher brain functions, such as cognitive-emotional changes including hyperactivity and anxiety-like behavior, and that the effects were greater in immunotoxicity, sex differences, and old age. We also found developmental neurotoxicity and transgenerational effects, and reported the weakness of the safety and risk assessment of current pesticides ahead of the rest of the world.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Kobe University, 19H04277
• Field-based toxicological mechanism analysis of emerging and re-emerging environmental pollution in Africa.
  Grants-in-Aid for Scientific Research Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
  09 Oct. 2018 - 31 Mar. 2022
  Ishizuka Mayumi
  In recent years, African countries have been promoting rapid resource development. As a result, rapid pollution of the environment has become apparent, and health hazards to ecosystems, livestock, and humans have been reported in some countries. For example, most of the 230,000 lead poisoning deaths worldwide occur in developing countries such as Africa, and the WHO has indicated that lead should be a priority. In this study, we analyzed exposure to heavy metals and pesticides using Zambia and South Africa as models to determine the actual effects on humans and animals that are occurring at the field level.
  Japan Society for the Promotion of Science, Fund for the Promotion of Joint International Research (Fostering Joint International Research (B)), Hokkaido University, 18KK0287
• Perfluorinated alkyl substances exposure and onset of puberty - birth cohort and in vitro studies
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
  01 Apr. 2018 - 31 Mar. 2022
  Ikeda Atsuko
  Per and polyfluorinated substances (PFAS) is a class of chemicals known for "endocrine disrupting” effects. A birth cohort study examined the effects of prenatal PFAS exposure on gonadal function and onset of puberty. Prenatal PFAS exposure lowered testosterone levels and increased progesterone and INSL3 levels at birth. PFTrDA delayed the age of menarche in girls. ESR1 polymorphisms may modulate the effects of PFAS on sexual differentiation. In vitro study, PFOA and PFNA showed agonist activity of ERalpha and PPARalpha. PFOA and PFNA were agonists of ERalpha and PPARalpha, whereas no agonist of antagonist activation of ERbeta, AR, GR, TR. Up or down regulation of about 800-intracellular gene expression were observed upon PFOA exposure, including PPARalpha receptors signaling genes and cytokines and IgE related genes.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 18H03035
• Evaluation of Chemical Susceptibility Diversity by mlAOP Concept and its Application to Understanding Insecticide Poisoning
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
  01 Apr. 2018 - 31 Mar. 2022
  IKENAKA Yoshinori
  In this study, we tested a new assessment concept, mlAOP, to evaluate species diversity in toxic effects. As a model compound, we focused on neonicotinoids (NN) and compared their neurotoxic effects on mice, zebrafish, and Xenopus. As a result, behavioral abnormalities and neurotransmitter disturbances were observed in both species at exposure levels below the non-toxic dose (NOAEL). Furthermore, in order to evaluate the sensitivity of a wide range of wild animal species, this study constructed an evaluation system focusing on skin fibroblasts, and evaluated the effects of NN in diverse species.
  Clinical studies conducted to evaluate human exposure and health effects were the first in the world to identify the source of exposure to neonicotinoids.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, 18H04132
• Developing evaluation methods for the effects of ionic environmental pollutants on neurotransmitters
  Grants-in-Aid for Scientific Research Challenging Research (Exploratory)
  28 Jun. 2019 - 31 Mar. 2021
  Nomiyama Kei
  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. In this study, we developed a sensitive and accurate analytical method using liquid chromatography-mass spectrometry (LC-MS/MS) to clarify the effects of neonicotinoid administration on MAs in the brain. We orally administered the neonicotinoid imidacloprid to mice. The LC-MS/MS quantification of MAs in various brain regions by DPP derivatization, which was newly developed in this study, showed a decrease in some MA levels in the olfactory bulb and the striatum. Thus, in this study, we developed a new method for the sensitive detection of MAs by LC/MS using DPP derivatization.
  Japan Society for the Promotion of Science, Challenging Research (Exploratory), Ehime University, 19K22933
• Development of new "cocktail type" rodenticide
  Grants-in-Aid for Scientific Research Challenging Research (Exploratory)
  29 Jun. 2018 - 31 Mar. 2020
  Ishizuka Mayumi
  Currently, secondary damage to birds of prey from rodenticides is frequently occurring. Therefore, no effective and safe control measures exist for rodenticide-resistant rats. This is due to the lack of research on resistance acquisition mechanisms and the lack of methods for assessing susceptibility in wildlife. The purpose of this study was to elucidate the causes of the acquisition of rodenticide resistance and to obtain data that will contribute to the development of rodenticides and their conservation to non-target species. This study demonstrated that mutations in the binding pocket and within the binding pocket of vitamin K epoxide reductase contribute to the acquisition of resistance in wild rodents as a cause of rodenticide resistance, and revealed a new mechanism of resistance acquisition through enhanced NADPH production and subsequent activation of rodenticide metabolism by cytochrome P450.
  Japan Society for the Promotion of Science, Challenging Research (Exploratory), Hokkaido University, 18K19847
• Elucidation of species differences and adaptive evolution of chemical sensitivity in mammal and bird species
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
  01 Apr. 2016 - 31 Mar. 2020
  Ishizuka Mayumi
  We cloned P450 and UGT, the major pathways of xenobiotic metabolism in the liver, in mammals and birds, and characterized them enzymatically, identifying species in which UGT and ST are deficient or extremely inactive and the causes. In addition, anticoagulant rodenticides are currently used primarily for the control of exotic small mammals worldwide. Therefore, we evaluated the susceptibility of a wide range of animal species to rodenticides and clarified the differences in the metabolic capacity of P450 and UGT.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, 16H01779
• Contraction of wild-life iHep cell and development of the evaluation method for metabolism of the top predator
  Grants-in-Aid for Scientific Research Challenging Research (Exploratory)
  30 Jun. 2017 - 31 Mar. 2019
  Ikenaka Yoshinori
  The purpose of this study is to develop the evaluation method of metabolism, which is the key to chemical sensitivity, and to clarify the chemical metabolic ability of rare top predator. Fresh liver is required for the evaluation of metabolism, but rare species are difficult to obtain. Therefore, in this study, we attempted to differentiate and induce liver-like cells (iHep cells) from skin fibroblasts by direct reprogramming. First, as a result of this study, we succeeded in culturing fibroblasts of several top predators such as brown bear and Sea lion. Furthermore, as a result of attempting to induce iHep cells using cultured fibroblasts, it was found that the cells were transformed into epithelial cells expressing albumin by introducing a specific factor. In this study, it is highly probable that iHep cells were successfully generated starting from wild animals.
  Japan Society for the Promotion of Science, Challenging Research (Exploratory), Hokkaido University, 17K20038
• Development of diagnostic methods for subacute and chronic neonicotinoids intoxication and investigation of the pathogenesis of neonicotinoids intoxication
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
  01 Apr. 2015 - 31 Mar. 2019
  Taira Kumiko; KOMORI makiko; FUJIOKA kazutoshi; KAWAKAMI tomonori; ARIZONO kouji
  Seven neonicotinoids were separately administered to female NZ white rabbits; and the urine samples were collected after 12-48 hours. More than 20 metabolites, such as hydroxy-imidacloprid, N-desmethyl-acetamiprid, N-desmethyl-colthianidin, N-desmetyl-nitenpyram, and N-desmetyl-dinotefuran, were qualitatively detected from the urine samples by LC-TOFMS.
  We synthesized 13 metabolites, which were not commercially available, as standards substances and developed quantitative bioanalytical methods using LC-MS/MS.
  Then we collected urine samples from the general population, e.g. 46 from three- to six-year-old children in Nagano; 102 from Sri Lankan people, some with chronic kidney disease; and 78 from people in Ghana. The following compounds, imidacloprid, acetamiprid, thiacloporid, nitenpyram, thiamethoxam, clothianidin, dinotefuran, hydroxy-imidacloprid, N-desmethyl-acetamiprid, N-desmethyl-colthianidin, and N-desmethyl-nitenpyram were quantitatively detected from those urine samples.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Tokyo Women's Medical University, 15K00559
• Investigation of hepatic warfarin metabolism activity in rodenticide-resistant black rats (Rattus rattus)
  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
  01 Apr. 2016 - 31 Mar. 2018
  Ishizuka Mayumi
  Anti-blood coagulation rodenticides, such as warfarin, have been used all over the world. They inhibit vitamin K epoxide reductase (VKOR), which is necessary for producing several blood clotting factors. This inhibition by rodenticides results in lethal hemorrhage in rodents. However, heavy usage of these agents has led to the appearance of rodenticide-resistant rats. The mutation of the target enzyme of warfarin, VKOR, is considered as major cause for rodenticide resistance in wild rats. However, there have been few studies regarding the hepatic metabolism of warfarin. We investigated warfarin metabolism in resistant rats, and our results showed new mechanism for the rodenticide resistance in wild black rats in Japan.
  Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, 16K15034
• Elucidation of useful livestock/poultry for Pb source estimation and its molecular mechanisms underlying species differences by integrated metallomics approaches
  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
  01 Apr. 2016 - 31 Mar. 2018
  Nakayama Shouta; Ishizuka Mayumi; Ikenaka Yoshinori; Mizukawa Hazuki; Hirata Takafumi
  According to WHO, approximately 230,000 people annually die mainly from lead (Pb) poisoning derived from mineral deposits and affect the intellectual development of more than 600,000 children, but useful methods for estimating pollution sources have not been established. In this study, we aimed to elucidate useful livestock and poultry species for source estimation of Pb contamination. From the high precision lead isotope ratio analysis, it was revealed that it is possible to estimate the source of Pb contamination by using goats and chickens distributed in developing countries including Africa and also used as human food sources. Local distribution of Pb in mice was analyzed by LA-ICP-MS (laser ablation inductively coupled plasma mass spectrometry). High Pb accumulation in the hippocampus area of the brain and Pb accumulation at a higher concentration than in the cortex than the medulla of the kidney was revealed.
  Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, 16K16197
• Investigation of the cause of chronic kidney disease of unknown etiology and fluoride removal from drinking water in Sri Lanka
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
  01 Apr. 2015 - 31 Mar. 2018
  Kawakami Tomonori; TAFU Masamoto
  According to the measurement results of cadmium, lead, chromium and arsenic in drinking water, rice, tea leaves and urine, it was concluded that cadmium, lead, chromium and arsenic were not the cause of chronic kidney disease of unknown etiology (CKDu) prevailing in Sri Lanka. The diagnostic of the CKDu was consistent with that of neonicotinoid poisoning; however, the conclusive evidence of the relationship between neonicotinoid insecticides and CKDu was not found. A new electrolysis system using carbon electrodes to remove fluoride was installed in Anuradhapura to supply drinking water to the residents. The fluoride concentration was successfully reduced from 2.1 mg/L to 0.4 mg/L, which was well below the Sri Lankan standard of 1 mg/L. Two electrolysis systems using carbon electrodes followed by chicken bone char filters installed in Sri Lanka could remove fluoride to the level of 0 mg/L.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Toyama Prefectural University, 15H05120
• Elucidation for metabolic capacities of organologen compounds and assessment of thyroid function
  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
  01 Apr. 2015 - 31 Mar. 2018
  MIZUKAWA HAZUKI; ISHIZUKA Mayumi; IKENAKA Yoshinori; NAKAYAMA Shouta; TAKIGUCHI Mitsuyoshi; NOMIYAMA Kei
  To clarify the in vivo kinetics (absorption, distribution, metabolism, and excretion) of organohalogen compounds in cats, PCBs short-term administration test and long-term administration test of BDE 209 were carried out. Also, I have evaluated the influence on thyroid function and risk assessment by chemical and toxicological analysis. As a result, exposure to PCBs and BDE 209 not only affected thyroid function but also increased oxidative stress, disturbance of production of NADPH, disturbance of lipid metabolism function and immune function were expected.
  Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, 15K16132
• Risk assessment of vector control chemicals to wild animals and development of novel method to determine the chemical sensitivity
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
  01 Apr. 2015 - 31 Mar. 2018
  Ikenaka Yoshinori
  In this study, attention was paid to the KwaZulu-Natal state in South Africa, a vector control area in Africa, and its threat situation was investigated and toxicity impact assessment was conducted on living organisms.
  As a result of investigation focusing on poultry, the DDT concentration in the liver showed a very high value of 920 ng / g ww in the median and 14,400 ng / g ww in the maximum value. As a result of gene expression analysis by real-time RT-PCR method, it became clear that it affected genetic group involved in lipid metabolism, synthesis and sex steroid hormone synthesis. The results of this study suggest that DDT gives certain effects to the living body, suggesting the need to implement more appropriate Vector control in the future.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Principal investigator, Competitive research funding, 15H02825
• Species differences and evolution of phase II conjugation reaction and its cellular function
  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
  01 Apr. 2015 - 31 Mar. 2017
  Ikenaka Yoshinori
  UGTs are among the most important xenobiotic metabolizing enzymes that conjugate a wide range of endogenous and exogenous compounds. Previous studies showed that Felidae species and Pinnipedia species have very low UGT activities toward some phenolic compounds because of the UGT1A6 pseudogene and small numbers of UGT1A isozymes. In addition to the UGT1As, UGT2Bs isozymes also conjugate various endogenous and exogenous compounds. Results of UGT activity measurement indicated cats and pinniped species had very low activities toward these substrates. Furthermore, Felidae species had the same nonsense mutation in UGT2B, which suggested that Felidae UGT2B31 was also a pseudogene in addition to UGT1A6. Together with the lower activity of UGT1As, these findings of lower activity of UGT2B suggested that Felidae and some pinniped species have very low UGT activity toward a wide range of chemicals.
  Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, Principal investigator, Competitive research funding, 15K12213
• Ecological and human risk assessment of vector control pesticides
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
  01 Apr. 2014 - 31 Mar. 2017
  Ikenaka Yoshinori; SAKURAI Tatsuya; MIYABARA Yuichi; SHIMOZURU Michito; NAKAYAMA Shouta; MIZUKAWA Hazuki; Johan van Vuren; Vlok Wynand; Smit Nico; Grobler Paul; Beyene Yared; Teju Endale
  WHO recommended to use DDT for controlling Anopheles, and allow to use more than 5000 tons as indoor residual spraying (IRS) in developing countries mainly in Africa. On the other hand, DDT is well known chemical that is persistence in the environment and has long half-life, with carcinogenicity and endocrine disruption. IRS is considered low environmental burden because spraying occurs inside the house, however, there is insufficient research about the effect on human and animals. From our data, chicken accumulated very high concentration of DDT with the cancer risk for humans health. Moreover, wild rats was accumulated DDT with exceeded the levels that in experimentally exposed rat had cause the liver function disorder. Furthermore, I could detect DDTs from all the examined eggs from wild birds.
  These results indicated that DDT IRS that has been considered as low environmental impact has potential toxicological effects and environmental risks.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Principal investigator, Competitive research funding, 26304043
• Defence mechanism against environmental chemicals in livestock animals
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
  01 Apr. 2012 - 31 Mar. 2016
  ISHIZUKA MAYUMI; IKENAKA Yoshinori; TSUBOTA Toshio; KONNAI Satoru
  In livestock animals, we identified the enzymatic characters of cytochrome P450 as typical phase I enzyme for xenobiotics. We also analyzed glucronyltrasnferase and sulfotransferase dependent metabolites in urine samples from mammalians including livestock animals, to elucidate the ability of xenobiotic conjugating detoxification. In field surveillance at Asia and African countries, heavy metals are major accumulated environmental pollutants in cattle, and the accumulating pattern is unique in ruminants. In case of poultry species, we clarify the expressed cytochrome P450 and phase II enzymes in liver using transcriptome analyses method and in silico analyses, and we compared the structure of xenobiotic metabolizing enzymes in poultry species to those of mammals.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, Coinvestigator not use grants, Competitive research funding, 24248056
• Development of analytical method for the organohalogen metabolites elucidation of metavolic capacities and risk assessment in the pet cat
  Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity start-up
  30 Aug. 2013 - 31 Mar. 2015
  MIZUKAWA Hazuki; ISHIZUKA Mayumi; IKENAKA Yoshinori; NAKAYAMA Shouta; TAKIGUCHI Mitsuyoshi; NOMIYAMA Kei
  This study was develop the analyzing method for hydroxylated polybrominated diphenyl ethers (OH-PBDEs) and the glucuronidation compounds of OH-PCBs using liquid chromatography tandem mass spectrometry (LC-MS/MS). Moreover, it was measured the glucuronidation activities using the liver microsomes of the cats. I also attempted the evaluation of metabolic capacities of PCBs and PBDEs in the cats.
  Japan Society for the Promotion of Science, Grant-in-Aid for Research Activity start-up, Hokkaido University, 25892001
• Monitoring of food contamination and surveillance of chemical hazard in African countries
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
  01 Apr. 2012 - 31 Mar. 2015
  ISHIZUKA Mayumi; IKENAKA Yoshinori
  Environmental pollution is a serious problem in most African countries. Persistent chemicals such as heavy metals, pesticides, dioxins, PCBs, etc. can be found not only in water, soil, air, plant, but also in the livestock animals. Monitoring these pollutant levels in food animals is of great importance to the wellbeing of all life forms. In this study, we measured accumulated levels of these environmental pollutants in animals and clarified the effects of chemical hazard on human and animals.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Coinvestigator not use grants, Competitive research funding, 24405004
• Toxicological Research in Africa; The risk assessment that paid attention to drug metabolism species specificity
  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
  2011 - 2012
  IKENAKA Yoshinori
  We paid attention to a drug metabolism phase II conjugation reaction and determined species specificity of pro-drug metabolism for the wild animal. Sulfate conjugation of pyrene was detected in the pigs which had been thought to have low sulfate conjugation activity by the screening using 11 kinds of mammalian urine. Also, as a result of kinetics analysis, it was found that the enzyme efficiency of the pig was higher than a rat. Whereas, in the investigation carried out in Africa, we obtained amphibians, mammals, avian urine and an organ. As a result of having performed chemical analysis mainly on heavy metal and pesticides, an extremely highly-concentrated chemical was detected in some areas, and the tendency that accumulated a chemical at the level that was higherthan other organism species in birds particularly was observed.
  Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, Principal investigator, Competitive research funding, 23710038
• Infection risk to wildlife populations and immune suppression induced by environmental chemicals
  Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity start-up
  2009 - 2010
  IKENAKA Yoshinori
  We investigated about "disease for wildlife caused by environmental chemicals", in particular "immunosuppression" focusing on at the field level. We did our investigation in Republic of Zambia the major industry of the country is mining activity. From our results, we found that due to mining activity, the inflammatory cytokines levels and oxidative stress marker levels in domestic cattle and wild rodents were consider affected by heavy metals exposure. Furthermore, we analyze the correlation between GIS heavy metal concentration data and immune disruption. The results indicated that we couldn't found any correlations among immune disruption, heavy metal concentration in soil, and MT expression levels. Our results suggested that other strong factors such as feeding habitat, infection are affected to the correlation.
  Japan Society for the Promotion of Science, Grant-in-Aid for Research Activity start-up, Hokkaido University, Principal investigator, Competitive research funding, 21810001
• Effects of environmental pollutants on cancer in wildlife
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
  2007 - 2010
  FUJITA Shoichi; IKENAKA Yoshinori; ISHIZUKA Mayumi; SAKAMOTO Kentaro
  We investigated bioaccumulation levels of environmental chemicals, e.g., carcinogens and pro-carcinogens, in wildlife and elucidated the effects of these environmental toxic compounds. We cloned cytochrome P450 1 subfamilies, arylhydrocarbon receptors and phase II enzymes, which contribute to activation or detoxification of carcinogens and procarcinogens, from bird and mammalian species including rare wildlife, and characterized these molecules. We also reported the molecular evolution of these enzymes and regulation receptors in wildlife.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, Coinvestigator not use grants, Competitive research funding, 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
  Grants-in-Aid for Scientific Research Grant-in-Aid for JSPS Fellows
  2007 - 2008
  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。
  Japan Society for the Promotion of Science, Grant-in-Aid for JSPS Fellows, 07J10117