Halothane-induced hepatic necrosis in triiodothyronine-pretreated rats.
Hepatic centrilobular necrosis developed in rats pretreated with triiodothyronine (T3) and then anesthetized with halothane, 1 per cent, for two hours at an ambient oxygen concentration. Increasing oxygen concentrations decreased the severity of the lesion, there being a significantly (P less than 0.05) less severe lesion with oxygen, 99 per cent, as compared with 21 per cent. Pretreatment with phenobarbital alone resulted in hepatic necrosis only when hypoxia (FIO2 0.14) was also present, and there was no significant worsening of the T3-induced lesion when phenobarbital was added at any oxygen concentration studied. However, the lesion produced by T3 and oxygen, 14 per cent, was significantly worse than the lesion produced by phenobarbital and oxygen, 14 per cent. Glutamic pyruvic transaminase (SGPT) was significantly elevated to 776 (+/- 226) U/1 in the T3-treated rats (10 mg/kg/day, orally) immediately after halothane anesthesia. There was a significant decrease in glutathione to 1.48 (+/- 0.06) mg/g liver 24 hours after T3 administration (1 mg/kg subcutaneously for five days), but no further decrease with continued T3 pretreatment or with halothane anesthesia. Pretreatment with T3 caused a significant decrease in cytochrome P-450 to 0.41 (+/- 0.01) nmol/mg microsomal protein, and halothane anesthesia caused a further significant decrease to 0.27 (+/- 0.04) nmol/mg microsomal protein. The mechanism for the hepatic toxicity of halothane in this model remains to be determined.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001835:Body Weight; D056486:Chemical and Drug Induced Liver Injury; D003577:Cytochrome P-450 Enzyme System; D004305:Dose-Response Relationship, Drug; D005978:Glutathione; D006221:Halothane; D008099:Liver / Q000473:pathology; D008297:Male; D009336:Necrosis; D011136:Polysorbates / Q000494:pharmacology; D051381:Rats; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology*
D011136:Polysorbates; D014284:Triiodothyronine; D003577:Cytochrome P-450 Enzyme System; D000410:Alanine Transaminase; D005978:Glutathione; D006221:Halothane