Knight E V, Chin B H, Ueng T H, Alvares A P
Drug Chem Toxicol. 1986;9(3-4):253-73. doi: 10.3109/01480548608998279.
The effects of one of the most widely used insecticides, carbaryl, on the hepatic cytochrome P-450-dependent monooxygenases were determined. Addition of carbaryl to liver microsomes from untreated or phenobarbital (PB)-pretreated rats resulted in a weak Type I binding spectrum. A much stronger spectral Type I interaction was observed when microsomes from 3-methylcholanthrene(3-MC)-treated rats were used. In vitro, carbaryl caused marked inhibition of ethylmorphine and benzphetamine N-demethylases, benzo(a)pyrene hydroxylase, 7-ethoxycoumarin and 7-ethoxyresorufin O-deethylase in liver microsomes. Kinetic studies demonstrated that carbaryl was a competitive inhibitor of ethylmorphine N-demethylase activity. Daily administration of carbaryl for 4 days by gavage or intraperitoneally resulted in no significant alterations in hepatic cytochrome P-450 levels, ethylmorphine N-demethylase or benzo(a)-pyrene hydroxylase activities. The lack of effect of carbaryl in vivo may be due to the rapid metabolism of the insecticide, such that the insecticide may not be present in the liver endoplasmic reticulum to cause the inhibitory effects observed in vitro.
测定了使用最广泛的杀虫剂之一西维因对肝脏细胞色素P - 450依赖性单加氧酶的影响。将西维因添加到未处理或经苯巴比妥（PB）预处理的大鼠肝脏微粒体中，产生了微弱的I型结合光谱。当使用经3 - 甲基胆蒽（3 - MC）处理的大鼠的微粒体时，观察到更强的I型光谱相互作用。在体外，西维因显著抑制肝脏微粒体中的N - 脱甲基酶、苯并芘羟化酶、7 - 乙氧基香豆素和7 - 乙氧基试卤灵O - 脱乙基酶。动力学研究表明，西维因是N - 脱甲基酶活性的竞争性抑制剂。通过灌胃或腹腔注射连续4天给予西维因，肝脏细胞色素P - 450水平、N - 脱甲基酶或苯并芘羟化酶活性均无显著变化。西维因在体内无作用可能是由于该杀虫剂的快速代谢，以至于杀虫剂可能不存在于肝脏内质网中从而无法产生体外观察到的抑制作用。
