Dalvi R R, Ashley W M
Drug Chem Toxicol. 1979;2(3):245-55. doi: 10.3109/01480547908998246.
The in vitro effect of various concentrations of captan on hepatic microsomal cytochrome P-450 from pehnobarbital-pretreated rats was studied. The I-50 value, namely the concentration of the inhibitor necessary to produce 50% loss of cytochrome P-450 was determined from theplotted inhibition curve. The presence of ethylenediaminetetraacetic acid (EDTA) in microsomal incubations prior to the addition of captan failed to prevent the loss of cytochrome P-450 by captan. In contrast, reduced glutathione (0.5 mM) added to microsomal incubations before captan (0.1 mM) afforded almost complete protection of cytochrome P-450 from captan inhibition. These data indicate that the inhibitory effect of captan on vitally important drug-metabolizing enzyme system, of which cytochrome P-450 is a major component, can be prevented by prior presence of reduced glutathione (GSH) but not of EDTA.
研究了不同浓度克菌丹对苯巴比妥预处理大鼠肝微粒体细胞色素P - 450的体外作用。从绘制的抑制曲线确定I - 50值，即产生50%细胞色素P - 450损失所需抑制剂的浓度。在添加克菌丹之前，微粒体孵育中存在乙二胺四乙酸（EDTA）并不能阻止克菌丹导致的细胞色素P - 450损失。相反，在加入0.1 mM克菌丹之前，向微粒体孵育中添加0.5 mM还原型谷胱甘肽，几乎能完全保护细胞色素P - 450免受克菌丹抑制。这些数据表明，克菌丹对以细胞色素P - 450为主要成分的极其重要的药物代谢酶系统的抑制作用，可以通过预先存在还原型谷胱甘肽（GSH）而不是EDTA来防止。
