The effects of enflurane on hepatic microsomal cytochrome P-450

Abstract

The effects of enflurane and pretreatment with phenobarbital or pyridine on hepatic cytochrome P-450 (P-450) were studied in male rats. The rats without pretreatment and those pretreated with phenobarbital or pyridine, were fasted for 24 hours and exposed to 1.2% enflurane at 10% or 21% oxygen for 2 hours. Each group consisted of 6 rats, and rats that were not exposed to enflurane served as control. In the group of rats pretreated with pyridine and exposed to enflurane at 10% oxygen, the content of P-450 and activity of aniline hydroxylation decreased significantly to approximately 61% and 62% of those of the control, respectively. Increases in the plasma level of AST and ALT, and centrilobular necrosis in hepatic tissue were also seen in this group. Administration of disulfiram to rats pretreated with pyridine inhibited the decrease of P-450 and hepatic injury. These results indicate that P-450 induced by pyridine was decomposed by exposure to enflurane at 10% oxygen and might cause hepatic injury.