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PubMed · 6872091

Cytochrome P-450 and halothane metabolism. Decrease in rat liver microsomal P-450 in vitro.

P A Krieter·R A van Dyke
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Abstract

Anaerobic in vitro incubation of microsomes from phenobarbital(PB)-induced rats with halothane results in an irreversible decrease of measurable cytochrome P-450. There is a parallel decrease in heme content under the same incubation conditions. However, microsomes from 3-methylcholanthrene(3-MC)-induced or untreated animals do not show a reduction in cytochrome P-450 content. Aerobic incubation with halothane results in a decrease of cytochrome P-450 which can be completely reversed by dialysis or the addition of potassium ferricyanide. These latter treatments only partially restore the cytochrome P-450 levels following anaerobic incubations. The decrease in cytochrome caused by halothane is not associated with measureable heme N-alkyl adduct formation; lipid peroxidation does not play a role as indicated by the lack of effect of 1 mM EDTA or a decrease in glucose-6-phosphatase activity. Halothane metabolites are bound irreversibly to microsomal protein as determined by gel electrophoresis only when the oxygen concentration is very low. The mechanism of cytochrome P-450 decrease is consistent with the formation of a reactive metabolite which binds to the protein portion and also destroys heme.

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AnimalsCarbon TetrachlorideCytochrome P-450 Enzyme SystemHalothaneHemeIn Vitro TechniquesMaleMicrosomes, LiverRatsRats, Inbred StrainsJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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P A Krieter, R A van Dyke. 1983. Cytochrome P-450 and halothane metabolism. Decrease in rat liver microsomal P-450 in vitro.. https://doi.org/10.1016/0009-2797(83)90051-0

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