Protective Effect of Glutathione on theIn VitroInhibition of Hepatic Cytochrome P-450 by Captan

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Abstract
The in vitro effect of various concentrations of captan [fungicide] on hepatic microsomal cytochrome P-450 from phenobarbital-pretreated rats was studied. The I-50 value [concentration of the inhibitor necessary to produce 50% loss of cytochrome P-450] was determined from the plotted inhibition curve. The presence of EDTA in microsomal incubations prior to the addition of captan failed to prevent the loss of cytochrome P-450 by captan. 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. The inhibitory effect of captan on the drug-metabolizing enzyme system, of which cytochrome P-450 is a major component, can evidently be prevented by prior presence of reduced glutathione (GSH) but not of EDTA.