Sensitivity of the rat liver microsomal oxidation of pyrazole to antibody raised against the ethanol-inducible rabbit liver cytochrome P-450 isozyme

L. A. Clejan, D. R. Koop, A. I. Cederbaum

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Pyrazole is oxidized to 4-hydroxypyrazole by rat liver microsomes in a cytochrome P-450-dependent reaction and this oxidation can be increased by prior treatment of rats with pyrazole, 4-methylpyrazole, or chronic ethanol feeding. The induction pattern suggests that pyrazole may be an effective substrate for oxidation by P-450 IIE.1. this P-450 isozyme is recognized by antibody (anti-3a IgG) raised against the ethanol-inducible P-450 in rabbits. Experiments were carried out to evaluate the ability of anti-3a IgG to inhibit pyrazole oxidation by microsomes from controls and from rats treated with inducers of P-450 IIE.1. Immunoblots with anti-3a IgG or with the anti-pyrazole P-450 IgG were identical and indicated increased staining of the pyrazole P-450 with microsomes from rats treated with pyrazole, 4-methylpyrazole, or ethanol, relative to saline controls; very little staining occurred with microsomes from pair-fed controls or phenobarbital-treated rats. Rates of pyrazole oxidation were highest with microsomes from rats treated with the inducer of P-450 IIE.1 and lowest with pair-fed controls or rats treated with phenobarbital. Anti-3a IgG produced about a 60% decrease of pyrazole oxidation in microsomes from rats treated with inducers of P-450 IIE.1 and about a 25% decrease with the saline controls; no inhibition was found with microsomes from the phenobarbital-treated rats. The anti-3a IgG-resistant rate of pyrazole oxidation was similar with all the microsomal preparations, and was not due to interaction of pyrazole with hydroxyl radicals. The anti-3a IgG-sensitive rate of pyrazole oxidation was increased 4- to 5-fold after treatment of rats with pyrazole, 4-methylpyrazole, or ethanol, indicating that the increased oxidation of pyrazole caused by these agents is due to induction of P-450 IIE.1.

Original languageEnglish (US)
Pages (from-to)694-698
Number of pages5
JournalDrug Metabolism and Disposition
Volume17
Issue number6
StatePublished - Dec 1 1989

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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