Cytochrome P-450-dependent covalent binding of carbon disulfide to rat liver microsomal protein in vitro and its prevention by reduced glutathione.
Carbon disulfide, a hepatotoxic solvent, is metabolized by liver microsomal enzymes to reactive sulfur atoms which get bound to the microsomal enzymes, causing inhibition of the enzyme system. These studies were carried out to examine whether glutathione can protect the liver enzymes from the sulfur binding and against carbon disulfide toxicity. When liver microsomes isolated from phenobarbital-pretreated rats were incubated with 35S-CS2, NADPH and glutathione, almost 60% decrease in sulfur binding to microsomal protein was observed under the experimental conditions. It was further observed that the addition of glutathione to microsomal incubations resulted in almost complete recovery of the activity of the enzyme system as measured by cytochrome P-450 concentration and benzphetamine metabolism. The data suggest that the presence of glutathione in sufficient amount in the liver of subject exposed to CS2 may significantly decrease the liver toxicity of this highly toxic compound.
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Toxicology Laboratory, School of Veterinary Medicine, Tuskegee University, AL 36088.
D000818:Animals; D001589:Benzphetamine / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects; D002246:Carbon Disulfide / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005978:Glutathione / Q000494:pharmacology*; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D001589:Benzphetamine; D003577:Cytochrome P-450 Enzyme System; D005978:Glutathione; D002246:Carbon Disulfide