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dc.contributor.authorKhidkhan, Kraisiri
dc.contributor.authorIkenaka, Yoshinori
dc.contributor.authorIchise, Takahiro
dc.contributor.authorNakayama, Shouta M.M.
dc.contributor.authorMizukawa, Hazuki
dc.identifier.citationKhidkhan, K. et al. 2020. Interspecies differences in cytochrome P450-mediated metabolism of neonicotinoids among cats, dogs, rats, and humans. Comparative biochemistry and physiology. Part C. Toxicology and pharmacology, 239:Art. #108898. []en_US
dc.description.abstractNeonicotinoid 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 enzymesen_US
dc.subjectCytochrome P450en_US
dc.subjectSpecies variationsen_US
dc.subjectIn vitro microsomal assayen_US
dc.titleInterspecies differences in cytochrome P450-mediated metabolism of neonicotinoids among cats, dogs, rats, and humansen_US
dc.contributor.researchID27878368 - Ikenaka, Yoshinori

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