Interspecies differences in cytochrome P450-mediated metabolism of neonicotinoids among cats, dogs, rats, and humans
Interspecies differences in cytochrome P450-mediated metabolism of neonicotinoids among cats, dogs, rats, and humans
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DOI：
10.1016/j.cbpc.2020.108898
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发表时间：
2021-01-01
影响因子：
3.9
通讯作者：
Ishizuka, Mayumi
中科院分区：
文献类型：
--
作者：
Khidkhan, Kraisiri;Ikenaka, Yoshinori;Ishizuka, Mayumi
新烟碱类杀虫剂在世界各地用于农业和非农业目的。宠物直接接触兽医产品中的新烟碱，并通过环境污染。细胞色素P450(CYP)是最重要的外源代谢酶之一，可以氧化包括新烟碱在内的多种化学物质。然而，在大多数驯养的宠物物种中，新烟碱类代谢物的CYP活性和代谢物组成尚不清楚。我们的目标是揭示新烟碱类化合物(吡虫啉、氯硫菌素和扑草净)的代谢物和CYP活性在常见宠物物种(猫和狗)、人和大鼠之间的差异。结果表明，CYP介导的新烟碱代谢因物种和新烟碱种类的不同而不同。吡虫啉代谢动力学研究表明，大鼠体内吡虫啉氧化为4OH-吡虫啉的速率最高，而大鼠和人体内吡虫啉代谢为5OH-吡虫啉的酶动力学最高。Clothianidin在大鼠体内迅速代谢为1-甲基-3-硝基胍和dm-Clothianidin，但猫和人的Dm-Clothianidin生成量最低。与其他物种相比，人类在乙酰胺虫菊酯代谢中的CYP活性显著高于其他物种。然而，进一步的研究应该针对使用重组CYP酶来确定这些物种中新烟碱类化合物在肝脏代谢方面的差异。
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.