Ethanol-inducible cytochrome p450 in rabbits metabolizes enflurane

J. Hoffman, K. Konopka, C. Buckhorn, D. R. Koop, L. Waskell

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Following anaesthesia with enflurane, some patients receiving isoniazid have increased serum concentrations of fluoride ion, presumably because of induction of an isozyme of cytochrome P450 which is responsible for enflurane biodegradation. In rats, isoniazid and ethanol enhance metabolism of enflurane and also induce a form of cytochrome P450 which is homologous with a form of rabbit liver cytochrome P450 known as 3a. Isoniazid, ethanol and imidazole increase the concentration of cytochrome P450 3a in hepatic microsomes. We have pretreated rabbits with imidazole, the most potent of the three inducers of isozyme 3a, to determine if the hepatic microsomal metabolism of enflurane is enhanced and if purified isozyme 3a catalyses the oxidation of enflurane. Imidazole produced a 250% increase in the hepatic microsomal metabolism of enflurane, sevoflurane, methoxyflurane and the control substrate, aniline. Polyclonal antibodies to cytochrome P450 3a inhibited 90% of enflurane metabolism, but only 40 % of methoxyflurane biotransformation in the microsomes from imidazole-pretreated rabbits. Thus isozyme 3a or a structurally similar cytochrome P450 seemed to catalyse almost all microsomal metabolism of enflurane. In addition, purified cytochrome P450 3a catalysed the metabolism of enflurane, sevoflurane and methoxyflurane, and the oxidation of these anaesthetics by cytochrome P450 3a was stimulated four-fold by cytochrome b5, a protein which serves as an alternate source of electrons for some cytochrome P450 reactions.

Original languageEnglish (US)
Pages (from-to)103-108
Number of pages6
JournalBritish journal of anaesthesia
Volume63
Issue number1
DOIs
StatePublished - Jul 1989

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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