Paradoxical effects of perturbation of intracellular levels of glutathione on halothane-induced hepatotoxicity in hyperthyroid rats.
Exposure of hyperthyroid rats to halothane results in a centrilobular necrosis of the liver and an 11-fold increase in serum glutamate-pyruvate transaminase (SGPT) levels. These effects are not seen in euthyroid animals. Paradoxically, administration of diethylmaleate to hyperthyroid rats significantly decreased the levels of hepatic glutathione and blocked the halothane-induced hepatic necrosis as well as decreased the elevation of SGPT. In contrast, pretreatment of animals with N-acetylcysteine, an intracellular sulfhydryl repletor , significantly increased the severity of the halothane-induced hepatic necrosis and increased the elevation of SGPT. Similarly, cysteamine, another intracellular sulfhydryl repletor , also exacerbated halothane-induced liver injury. Halothane-induced hepatotoxicity is at least in part apparently regulated by cellular glutathione levels. Paradoxically, glutathione seems to be involved in the bioactivation rather than the detoxification of halothane.
D000111:Acetylcysteine / Q000633:toxicity; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D005978:Glutathione / Q000378:metabolism*; D006221:Halothane / Q000633:toxicity*; D006980:Hyperthyroidism / Q000378:metabolism*; D008099:Liver / Q000473:pathology; D008297:Male; D008298:Maleates / Q000633:toxicity; D051381:Rats; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013997:Time Factors; D014284:Triiodothyronine / Q000494:pharmacology
D008298:Maleates; D013438:Sulfhydryl Compounds; D014284:Triiodothyronine; D000410:Alanine Transaminase; C014476:diethyl maleate; D005978:Glutathione; D006221:Halothane; D000111:Acetylcysteine