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)
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 rodenti...
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Elsevier
2022-09-01
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Series: | Ecotoxicology and Environmental Safety |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651322008119 |
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author | 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 |
author_facet | 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 |
author_sort | Kazuki Takeda |
collection | DOAJ |
description | 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. |
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institution | Directory Open Access Journal |
issn | 0147-6513 |
language | English |
last_indexed | 2024-04-13T06:02:16Z |
publishDate | 2022-09-01 |
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series | Ecotoxicology and Environmental Safety |
spelling | doaj.art-4d9296e3730d43039848894925e469d82022-12-22T02:59:24ZengElsevierEcotoxicology and Environmental Safety0147-65132022-09-01243113971Toxicokinetic 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 Takeda0Kosuke Manago1Ayuko Morita2Yusuke K. Kawai3Nobuaki Yasuo4Masakazu Sekijima5Yoshinori Ikenaka6Takuma Hashimoto7Ryuichi Minato8Yusuke Oyamada9Kazuo Horikoshi10Hajime Suzuki11Mayumi Ishizuka12Shouta M.M. Nakayama13Laboratory of Toxicology, School of Veterinary Medicine, Kitasato University, E23–35-1, Towada, Aomori 034-0021, Japan; Department of Computer Science, Tokyo Institute of Technology, 4259-J3–1818, Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-0026, Japan; Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818, JapanLaboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818, JapanLaboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818, JapanDepartment of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, JapanDepartment of Computer Science, Tokyo Institute of Technology, 4259-J3–1818, Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-0026, JapanDepartment of Computer Science, Tokyo Institute of Technology, 4259-J3–1818, Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-0026, JapanLaboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818, Japan; Water Research Group, Unit for Environmental Sciences and Management, North-West University, 11 Hoffman Street, Potchefstroom 2531, South Africa; Translational Research Unit, Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan; One Health Research Center, Hokkaido University, Sapporo, JapanJapan Wildlife Research Center, Kotobashi 3–3-7, Sumida-ku, Tokyo 130-8606, JapanJapan Wildlife Research Center, Kotobashi 3–3-7, Sumida-ku, Tokyo 130-8606, JapanJapan Wildlife Research Center, Kotobashi 3–3-7, Sumida-ku, Tokyo 130-8606, JapanInstitute of Boninology, Azanishimachi, Chichijima, Tokyo 100-2101, JapanInstitute of Boninology, Azanishimachi, Chichijima, Tokyo 100-2101, JapanLaboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818, JapanLaboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818, Japan; School of Veterinary Medicine, The University of Zambia, Great East Road PO Box 32379, Lusaka, Zambia; Corresponding author at: Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate Faculty of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818, Japan.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.http://www.sciencedirect.com/science/article/pii/S0147651322008119Chemical sensitivityCytochrome P450Molecular dockingPharmacokineticsVitamin K epoxide reductase |
spellingShingle | 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 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) Ecotoxicology and Environmental Safety Chemical sensitivity Cytochrome P450 Molecular docking Pharmacokinetics Vitamin K epoxide reductase |
title | 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) |
title_full | 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) |
title_fullStr | 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) |
title_full_unstemmed | 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) |
title_short | 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) |
title_sort | toxicokinetic analysis of the anticoagulant rodenticides warfarin amp diphacinone in egyptian fruit bats rousettus aegyptiacus as a comparative sensitivity assessment for bonin fruit bats pteropus pselaphon |
topic | Chemical sensitivity Cytochrome P450 Molecular docking Pharmacokinetics Vitamin K epoxide reductase |
url | http://www.sciencedirect.com/science/article/pii/S0147651322008119 |
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