Halothane-induced Hepatic Necrosis in Triiodothyronine-pretreated Rats

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Abstract
Hepatic centrilobular necrosis developed in rats pretreated with triiodothyronine (T3) and then anesthetized with halothane, 1% for 2 h at an ambient O2 concentration. Increasing O2 concentrations decreased the severity of the lesion, yielding a significantly (P. < 0.04) less severe lesion with oxygen, 99% compared to 21%. Pretreatment with phenobarbital alone resulted in hepatic necrosis only when hypoxia (FIO2 [fractional O2 concentration in inspired gas] 0.14) was also present, and there was no significant worsening of the T3-induced lesion when phenobarbital was added at any O2 concentration studied. The lesion produced by T3 and O2, 14%, was significantly worse than the lesion produced by phenobarbital and O2, 14%. Glutamic pyruvic transaminase (SGPT) was significantly elevated to 776 (.+-. 226) U[units]/l in the T3-treated rats (10 mg/kg per day, orally) immediately after halothane anesthesia. There was a significant decrease in glutathione to 1.48 (.+-. 0.06) mg/g liver 24 h after T3 administration (1 mg/kg s.c. for 5 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.