Interspecies differences in cytochrome P450-mediated metabolism of neonicotinoids among cats, dogs, rats, and humans

Khidkhan, Kraisiri; Ikenaka, Yoshinori; Ichise, Takahiro; Nakayama, Shouta M. M.; Mizukawa, Hazuki; Nomiyama, Kei; Iwata, Hisato; Arizono, Koji; Takahashi, Keisuke; Kato, Keisuke; Ishizuka, Mayumi

Interspecies differences in cytochrome P450-mediated metabolism of neonicotinoids among cats, dogs, rats, and humans

Khidkhan, Kraisiri; Ikenaka, Yoshinori; Ichise, Takahiro et al.

Comparative biochemistry and physiology Part C: Toxicology & pharmacology, 2021, 239, 108898

Permalink : https://hdl.handle.net/2115/83753

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アクセス権	open access
URI	https://hdl.handle.net/2115/83753
タイトル	Interspecies differences in cytochrome P450-mediated metabolism of neonicotinoids among cats, dogs, rats, and humans
著者	Khidkhan, Kraisiri ; Ikenaka, Yoshinori ; Ichise, Takahiro ; Nakayama, Shouta M. M. ; Mizukawa, Hazuki ; Nomiyama, Kei ; Iwata, Hisato ; Arizono, Koji ; Takahashi, Keisuke ; Kato, Keisuke ; Ishizuka, Mayumi
著者名 Khidkhan, Kraisiri
著者名 Ikenaka, Yoshinori
著者名 Ichise, Takahiro
著者名 Nakayama, Shouta M. M.
著者名 Mizukawa, Hazuki
著者名 Nomiyama, Kei
著者名 Iwata, Hisato
著者名 Arizono, Koji
著者名 Takahashi, Keisuke
著者名 Kato, Keisuke
e-Rad_Researcher 50332474 著者名 Ishizuka, Mayumi
言語	英語
キーワード	Neonicotinoids
	Cytochrome P450
	Species variations
	In vitro microsomal assay
発行日	2021-01
出版者	Elsevier
収録物名	Comparative biochemistry and physiology Part C: Toxicology & pharmacology
巻(号)	239
ページ	108898
抄録	Neonicotinoid insecticides are used for agricultural and non-agricultural purposes worldwide. Pets are directly exposed to neonicotinoids in veterinary products and through environmental contamination. Cytochrome P450 (CYP) is among the most significant xenobiotic metabolizing enzymes that oxidizes several chemicals, including neonicotinoids. However, CYP activities and metabolite compositions of neonicotinoid metabolites are unknown in most domesticated pet species. Our objectives were to reveal the differences in metabolites of neonicotinoids (imidacloprid, clothianidin, and acetamiprid) and CYP activities among common pet species (cats and dogs), humans, and rats. The results indicated that the CYP-mediated neonicotinoid metabolism was different depending on species and each neonicotinoid. Among these four species, the kinetics of imidacloprid metabolism indicated that rats have the highest rate of oxidation of imidacloprid to 4OH-imidacloprid, while the greatest enzyme kinetics of imidacloprid metabolism to 5OH-imidacloprid were found in rats and humans. Clothianidin was rapidly metabolized to 1-methyl-3-nitroguanidine and dm-clothianidin in rats, but cats and humans showed the lowest formation of dm-clothianidin. CYP activities in metabolism of acetamiprid to dm-acetamiprid and N-acetyl-acetamiprid were determined to be significantly higher in humans compared to other species. However, further studies should be targeted at identifying the differences in hepatic metabolism of neonicotinoids in these species using recombinant CYP enzymes.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	1532-0456
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.cbpc.2020.108898