In vitro effects of halothane exposure on hepatic microsomal cytochrome P-450 in rats

Abstract

Hepatic microsomes were collected from male rats in which hepatic microsomes enzymes were induced by phenobarbital (PB) and untreatend rats. Microsomes were deoxygenated by vacuum-freezing and exposed to 2% or 10% halothane and then incubated in a 37°C bath for 5 or 20 minutes. Microsomal enzyme contents and enzyme activities were measured. The contents of cytochrome P-450 were decreased in PB-induced microsomes (PB-microsomes) and the decrease was greater with 10% halothane or 20-minute incubation than with 2% halothane or 5-minute incubation. The contents of cytochrome P-450 in non-PB-microsomes were also decreased by 10% halothane. Heme contents were decreased in PB-microsomes by 10% halothane, and in non-PB-microsomes by 20-minute incubation with 2% halothane. The activities of aminopyrine demethylation were decreased both in PB and non-PB-microsomes and the decrease was greater with 10% halothane. The activities of aniline hydroxylation were decreased in PB and non-PB-microsomes, and after 20-minute incubation. The contents of cytochrome b₅, the tetrabutylic acid reacting substances and the activities of cytochrome P-450 reductase were not changed.
The decreases of microsomal cytochrome P-450 and microsomal enzyme activities by halothane exposure in deoxygenated states might be related to hepatic injury following halothane anesthesia.