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)

• Published in: Ecotoxicology and Environmental Safety
• 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: Article in Journal/Newspaper
• Language: English
• Published: Elsevier
• Subjects: Chemical sensitivity; Cytochrome P450; Molecular docking; Pharmacokinetics; Vitamin K epoxide reductase; 649; Rattus rattus
• Online Access: http://hdl.handle.net/2115/87331; https://doi.org/10.1016/j.ecoenv.2022.113971

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.