Alteration of hepatic glutathione S-transferases and release into serum after treatment with bromobenzene, carbon tetrachloride, or N-nitrosodimethylamine.
The effects of bromobenzene, carbon tetrachloride, and N-nitrosodimethylamine (DMN) on hepatic glutathione S-transferase activity were studied in untreated and in phenobarbital- or ethanol-treated rats. In phenobarbital-treated rats, the isozymic composition of the hepatic cytosolic glutathione S-transferases was changed after giving hepatotoxic chemicals; glutathione S-transferases 2-2(AA), 3-3(A), 1-2(B), 3-4(C), and 4-4 + 5-5(D + E) were present in cytosol from control rats, but only glutathione S-transferases cochromatographing with transferases 4-4 + 5-5(D + E) were detected in rats given carbon tetrachloride or bromobenzene. A marked decrease in hepatic and an increase in serum glutathione S-transferase activity were also observed after carbon tetrachloride or bromobenzene treatment, but little change was seen after giving DMN. On the contrary, in untreated or ethanol-treated rats, DMN administration decreased hepatic glutathione S-transferase activity and caused an elevation in serum glutathione S-transferase activity. The isozymic composition of the hepatic cytosolic glutathione S-transferases after giving DMN to untreated rats was also altered, but the alteration was much less than that observed after giving carbon tetrachloride or bromobenzene to phenobarbital-treated rats. The elevation in serum glutathione S-transferase activity was accompanied by an increase in both serum glutamate-pyruvate transaminase activity and serum bilirubin concentrations. Thus, hepatic glutathione S-transferase activity was altered and released into serum after giving hepatotoxic chemicals, and the alteration in glutathione S-transferase activity was dependent on treatment with phenobarbital or ethanol.
D000818:Animals; D001969:Bromobenzenes / Q000633:toxicity*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D003600:Cytosol / Q000201:enzymology; D004128:Dimethylnitrosamine / Q000633:toxicity*; D000431:Ethanol / Q000494:pharmacology; D005982:Glutathione Transferase / Q000032:analysis* / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001969:Bromobenzenes; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; C032036:bromobenzene; D005982:Glutathione Transferase; D004128:Dimethylnitrosamine; D010634:Phenobarbital