Changes in hepatic glutathione concentration modify cadmium-induced hepatotoxicity.
Cd has a strong affinity for sulfhydryl groups and is hepatotoxic. Thus, to further understand the mechanism of Cd-induced liver injury, the effect of increased and decreased hepatic glutathione (GSH) concentration on Cd-induced liver injury was examined. Liver GSH was lowered by pretreating rats with phorone (250 mg/kg, ip) or diethyl maleate (0.85 mg/kg, ip) 2 hr prior to challenge with various doses of Cd. Ten hours after Cd (1) 40-80% of the rats pretreated with phorone or diethyl maleate and challenged with 1.0-2.0 mg Cd/kg died whereas no mortality was observed in the control group; (2) plasma enzyme activities of alanine (ALT) and aspartate (AST) aminotransferase and sorbitol dehydrogenase (SDH) were markedly increased in phorone and diethyl maleate-pretreated rats challenged with Cd (0.7-2.0 mg/kg) versus control rats; and (3) moderate changes in liver histology were observed in corn oil pretreated and Cd challenged rats, while prior depletion of GSH potentiated histopathologic changes in liver produced by Cd alone. Another group of rats received cysteine (1.9 g/kg, po) 3 hr prior to injection of a lethal dose of Cd. Cysteine pretreatment increased liver GSH levels by 22% 3 hr after administration and attenuated Cd-induced liver injury as evidenced by marked decreases in plasma ALT, AST, and SDH activities. Pathological changes in liver were also reduced. These data indicate that liver reduced GSH concentration is important in modulating Cd-induced hepatotoxicity.
D000409:Alanine / Q000097:blood; D000818:Animals; D001224:Aspartic Acid / Q000097:blood; D002105:Cadmium Poisoning / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury; D003545:Cysteine / Q000494:pharmacology; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism*; D007659:Ketones / Q000494:pharmacology; D007064:L-Iditol 2-Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism; D008297:Male; D008298:Maleates / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D000637:Transaminases / Q000097:blood; D014280:Triglycerides / Q000097:blood
D007659:Ketones; D008298:Maleates; D014280:Triglycerides; D001224:Aspartic Acid; C018637:phorone; D007064:L-Iditol 2-Dehydrogenase; D000637:Transaminases; C014476:diethyl maleate; D005978:Glutathione; D003545:Cysteine; D000409:Alanine