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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)

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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)
Authors: Takeda, Kazuki Browse this author
Manago, Kosuke Browse this author
Morita, Ayuko Browse this author
Kawai, Yusuke K. Browse this author
Yasuo, Nobuaki Browse this author
Sekijima, Masakazu Browse this author
Ikenaka, Yoshinori Browse this author →KAKEN DB
Hashimoto, Takuma Browse this author
Minato, Ryuichi Browse this author
Oyamada, Yusuke Browse this author
Horikoshi, Kazuo Browse this author
Suzuki, Hajime Browse this author
Ishizuka, Mayumi Browse this author →KAKEN DB
Nakayama, Shouta M. M. Browse this author →KAKEN DB
Keywords: Chemical sensitivity
Cytochrome P450
Molecular docking
Pharmacokinetics
Vitamin K epoxide reductase
Issue Date: 15-Aug-2022
Publisher: Elsevier
Journal Title: Ecotoxicology and environmental safety
Volume: 243
Start Page: 113971
Publisher DOI: 10.1016/j.ecoenv.2022.113971
Abstract: 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 pse-laphon), but little is known regarding its sensitivity to rodenticides. In this study, the Egyptian fruit bats (Rou-settus 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.
Type: article
URI: http://hdl.handle.net/2115/87331
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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