Bromobenzene and p-bromophenol toxicity and covalent binding in vivo.
A hepatotoxic dose of bromobenzene (3 mmoles/kg) decreases hepatic glutathione concentration in rats by approximately 80% within 5 hr following ip injection. A major bromobenzene metabolite, p-bromophenol at a similar dose did not significantly alter hepatic glutathione levels compared to controls. Twenty four hr after administration, serum glutamate pyruvate transaminase (SGPT) levels were significantly increased by bromobenzene but not by p-bromophenol. After 14C-bromobenzene administration, a significant amount of covalently bound radiolabel was detected in liver, kidney and small intestine. A small amount of covalently bound radiolabel was also detected in the lung. After a similar dose of 14C-bromophenol, covalently bound radiolabel was found in liver (62% of the amount detected with 14C-bromobenzene) and smaller amounts were detected in kidney, small intestine and lung. These data are consistent with the view that the hepatotoxicity and glutathione depleting ability of bromobenzene are mediated mainly by bromobenzene-3,4-oxide rather than by chemically reactive metabolites of p-bromobenzene. Covalently bound radiolabel from 14C-bromobenzene, however, may be derived from both bromobenzene-3,4-oxide and the nontoxic reactive metabolites of p-bromophenol.
D000818:Animals; D001665:Binding Sites; D001969:Bromobenzenes / Q000378:metabolism / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010636:Phenols / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D001969:Bromobenzenes; D010636:Phenols; D005978:Glutathione; C032037:4-bromophenol