Protective effect of glutathione on the in vitro inhibition of hepatic cytochrome P-450 by captan.
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.
D000818:Animals; D002215:Captan / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D004492:Edetic Acid / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology*; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010545:Peroxides / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats
D065607:Cytochrome P-450 Enzyme Inhibitors; D010545:Peroxides; D011506:Proteins; D004492:Edetic Acid; D002215:Captan; D005978:Glutathione