Liver injury following halothane anesthesia in phenobarbital-pretreated rats

Abstract

Linear foci of centrolobular necrosis on the posterior aspect of the liver were consistently produced by 5 hr of anesthesia with 0.85% halothane in young male rats pretreated with phenobarbital (PBT: 1 g/l. drinking water) for 30 days. Microsomes isolated from livers of these animals immediately upon completion of anesthesia had elevated lipid-conjugated diene and decreased cytochrome P-450 content and 14C-glycine incorporation into protein in vivo. Lipid-conjugated dienes and glycine incorporation, but not P-450, returned to pre-anesthesia levels within 2 hr. None of these alterations were evident after anesthesia in livers of saline-pretreated rats (0.23 g NaCl/l. drinking water). Aside from the persistence of decreased animals, alterations in lipid-conjugated diene and glycine incorporation did not occur after repeated anesthesia at 48-hr intervals, nor was hepatic necrosis as evident, although anesthesia recovery times increased significantly. These findings indicate that metabolites of halothane are directly hepatotoxic and that repeated anesthesia with halothane at 2-day intervals decreases its hepatotoxic effect—presumably by interfering with its metabolism to toxic metabolites by the endoplasmic reticulum. Similar morphologic lesions can also be produced in PBT-pretreated animals by minute doses of CCl 4.