Catinot R, Hoellinger H, Sonnier M, Pichon J
CNRS-INSERM, UA 400, Faculté de Médecine, Paris, France.
Arch Toxicol. 1989;63(3):214-20. doi: 10.1007/BF00316371.
Phenobarbital-induced rat liver homogenate and microsomes were used to study covalent binding of 14C-labelled (at the alcohol moiety) cismethrin, 14C-labelled (at the alcohol and acid moieties) cypermethrin, and 14C-labelled (at the alcohol and acid moieties) deltamethrin. Covalent binding was dependent on pyrethroid concentration. With liver homogenate, inhibition of esterases by tetraethylpyrophosphate and of mitochondrial respiration by rotenone or potassium cyanide only slightly altered the covalent binding level. With microsomes, inhibition of cytochrome P-450 and mixed function oxidases by carbon monoxide and piperonyl butoxide reduced the covalent binding so far as to be nearly absent. Eighty percent inhibition of epoxide hydrolase decreased the covalent binding by 50%. The comparison of data between alcohol and acid labelling of the same pyrethroid suggested that, in vitro, the whole molecule is bound to proteins and that hydrolysis can occur afterwards. The experiments stress the role of cytochrome P-450-dependent monoxygenases in the covalent binding process.
使用苯巴比妥诱导的大鼠肝脏匀浆和微粒体来研究14C标记（在醇部分）的顺式氯菊酯、14C标记（在醇和酸部分）的氯氰菊酯以及14C标记（在醇和酸部分）的溴氰菊酯的共价结合。共价结合取决于拟除虫菊酯的浓度。对于肝脏匀浆，焦磷酸四乙酯对酯酶的抑制以及鱼藤酮或氰化钾对线粒体呼吸的抑制仅略微改变共价结合水平。对于微粒体，一氧化碳和胡椒基丁醚对细胞色素P - 450和混合功能氧化酶的抑制使共价结合减少到几乎不存在的程度。环氧水解酶80%的抑制使共价结合减少50%。对同一拟除虫菊酯的醇和酸标记数据的比较表明，在体外，整个分子与蛋白质结合，随后可能发生水解。这些实验强调了细胞色素P - 450依赖性单加氧酶在共价结合过程中的作用。
