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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fthokunivhus:oai:eprints.lib.hokudai.ac.jp:2115/87331 2023-05-15T18:05:35+02:00 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) 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. http://hdl.handle.net/2115/87331 https://doi.org/10.1016/j.ecoenv.2022.113971 eng eng Elsevier http://hdl.handle.net/2115/87331 Ecotoxicology and environmental safety, 243: 113971 http://dx.doi.org/10.1016/j.ecoenv.2022.113971 Chemical sensitivity Cytochrome P450 Molecular docking Pharmacokinetics Vitamin K epoxide reductase 649 article fthokunivhus https://doi.org/10.1016/j.ecoenv.2022.113971 2022-12-02T01:01:34Z 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. Article in Journal/Newspaper Rattus rattus Hokkaido University Collection of Scholarly and Academic Papers (HUSCAP) Ecotoxicology and Environmental Safety 243 113971 |
institution |
Open Polar |
collection |
Hokkaido University Collection of Scholarly and Academic Papers (HUSCAP) |
op_collection_id |
fthokunivhus |
language |
English |
topic |
Chemical sensitivity Cytochrome P450 Molecular docking Pharmacokinetics Vitamin K epoxide reductase 649 |
spellingShingle |
Chemical sensitivity Cytochrome P450 Molecular docking Pharmacokinetics Vitamin K epoxide reductase 649 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. 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) |
topic_facet |
Chemical sensitivity Cytochrome P450 Molecular docking Pharmacokinetics Vitamin K epoxide reductase 649 |
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 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. |
format |
Article in Journal/Newspaper |
author |
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. |
author_facet |
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. |
author_sort |
Takeda, Kazuki |
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_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_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_sort |
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) |
publisher |
Elsevier |
url |
http://hdl.handle.net/2115/87331 https://doi.org/10.1016/j.ecoenv.2022.113971 |
genre |
Rattus rattus |
genre_facet |
Rattus rattus |
op_relation |
http://hdl.handle.net/2115/87331 Ecotoxicology and environmental safety, 243: 113971 http://dx.doi.org/10.1016/j.ecoenv.2022.113971 |
op_doi |
https://doi.org/10.1016/j.ecoenv.2022.113971 |
container_title |
Ecotoxicology and Environmental Safety |
container_volume |
243 |
container_start_page |
113971 |
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1766177063434190848 |