In vitro metabolism of carbofuran by human, mouse, and rat cytochrome P450 and interactions with chlorpyrifos, testosterone, and estradiol

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• 作者：Usmani ; Khawja A. ; Hodgson ; Ernest ; Rose ; Randy L.
• 关键词：Carbofuran ; Metabolism ; Human liver microsomes ; Cytochrome P450 ; CYP3A4 ; Testosterone ; Interactions
• 刊名：Chemico-Biological Interactions
• 出版年：2004
• 出版时间：December 7, 2004
• 年：2004
• 卷：150
• 期：3
• 页码：221-232
• 全文大小：436 K

文摘

Carbofuran is a carbamate pesticide used in agricultural practice throughout the world. Its effect as a pesticide is due to its ability to inhibit acetylcholinesterase activity. Though carbofuran has a long history of use, there is little information available with respect to its metabolic fate and disposition in mammals. The present study was designed to investigate the comparative in vitro metabolism of carbofuran from human, rat, and mouse liver microsomes (HLM, RLM, MLM, respectively), and characterize the specific enzymes involved in such metabolism, with particular reference to human metabolism. Carbofuran is metabolized by cytochrome P450 (CYP) leading to the production of one major ring oxidation metabolite, 3-hydroxycarbofuran, and two minor metabolites. The affinity of carbofuran for CYP enzymes involved in the oxidation to 3-hydroxycarbofuran is significantly less in HLM (K_m