Effects of liver injury and cholestasis on microsomal enzyme activities and metabolism of halothane, enflurane and methoxyflurane in vivo in rats.
1. Cholestasis (bile-duct ligation 24 h before) had no effect on rat liver microsomal protein content, cytochrome P-450 or cytochrome 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 greater than halothane greater than 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 (30-50% 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.
D000777:Anesthetics / Q000378:metabolism*; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology; D002779:Cholestasis / Q000201:enzymology*; D004737:Enflurane / Q000378:metabolism; D006207:Half-Life; D006221:Halothane / Q000378:metabolism; D008107:Liver Diseases / Q000201:enzymology*; D008297:Male; D008733:Methoxyflurane / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
D000777:Anesthetics; D008733:Methoxyflurane; D004737:Enflurane; D006221:Halothane