Effects of liver injury and cholestasis on microsomal enzyme activities and metabolism of halothane, enflurane and methoxyfluranein vivoin rats

Abstract

1. Cholestasis (bile-duct ligation 24 h before) had no effect on rat liver microsomal protein content, cytocrhome P-450 or cytocrhome c reductase activity, but depressed aniline hydroxylase activity and aminopyrine demethylase less so. Pretreatment with CCl₄ (24 h before) decreased rat liver cytochrome P-450, aniline hydroxylase and aminopyrine demethylase. 2. Halothane, enflurane and methoxyflurane are metabolized via different pathways, resulting in different metabolic elimination rates in our exposure system (methoxyflurane > halothane >enflurane). Elimination half-lives of the three compounds from the atmosphere of the exposure system were three times longer in CCl₄-injured rats; cholestasis had a weaker effect (30-50d % increase). 3. Dehalogenation of enflurane, which is the preferred pathway, is affected to the same extent as the cytochrome P-450-dependent hydroxylation of halothane and the O-dealkylation of methoxyflurane.