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

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Title: Interspecies differences in cytochrome P450-mediated metabolism of neonicotinoids among cats, dogs, rats, and humans
Authors: Khidkhan, Kraisiri Browse this author
Ikenaka, Yoshinori Browse this author
Ichise, Takahiro Browse this author
Nakayama, Shouta M. M. Browse this author
Mizukawa, Hazuki Browse this author
Nomiyama, Kei Browse this author
Iwata, Hisato Browse this author
Arizono, Koji Browse this author
Takahashi, Keisuke Browse this author
Kato, Keisuke Browse this author
Ishizuka, Mayumi Browse this author →KAKEN DB
Keywords: Neonicotinoids
Cytochrome P450
Species variations
In vitro microsomal assay
Issue Date: Jan-2021
Publisher: Elsevier
Journal Title: Comparative biochemistry and physiology Part C: Toxicology & pharmacology
Volume: 239
Start Page: 108898
Publisher DOI: 10.1016/j.cbpc.2020.108898
Abstract: 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.
Rights: © 2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
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)

Submitter: 石塚 真由美

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