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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Bibliographic Details
Published in:	Ecotoxicology and environmental safety Vol. 243; p. 113971
Main Authors:	Takeda, Kazuki, Manago, Kosuke, Morita, Ayuko, Kawai, Yusuke K., Yasuo, Nobuaki, Sekijima, Masakazu, Ikenaka, Yoshinori, Hashimoto, Takuma, Minato, Ryuichi, Oyamada, Yusuke, Horikoshi, Kazuo, Suzuki, Hajime, Ishizuka, Mayumi, Nakayama, Shouta M.M.
Format:	Journal Article
Language:	English
Published:	Elsevier Inc 15-09-2022 Elsevier
Subjects:	Chemical sensitivity Cytochrome P450 Molecular docking Pharmacokinetics Vitamin K epoxide reductase Chemical sensitivity Vitamin K epoxide reductase Pharmacokinetics Cytochrome P450 Molecular docking
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Summary:	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. [Display omitted] •Sensitivity of fruit bats to two anticoagulant rodenticides was evaluated.•The bats excreted diphacinone slowly and showed similar sensitivity to rats.•The bats excreted warfarin faster than the rats and showed lower sensitivity.•VKORC1; target enzyme of fruit bats binds strongly to diphacinone in in silico.•Susceptibility assessments on a species- & chemical-specific basis are important.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0147-6513 1090-2414
DOI:	10.1016/j.ecoenv.2022.113971