Increased microsomal oxidation of alcohols after pyrazole treatment and its similarities to the induction by ethanol consumption

Microsomes isolated from rats treated for 3 days with 200 mg/kg body wt. per day of pyrazole, a potent inhibitor of alcohol dehydrogenase, catalyzed the oxidation of ethanol and 2-butanol at rates 2-3-fold higher than saline controls. The increase eas blocked by carbon monoxide, and was not associated with an increase in the oxidation of aminopyrine or in the content of cytochrome P-450, suggesting the possibility of an induction of an alcohol-preferring cytochrome P-450 by pyrazole. Microsomes from the pyrazole-treated rats displayed a stereochemical preference for the oxidation of the (+)-2-butanol isomer over the (-)-2-butanol isomer, which was blocked by carbon monoxide, and also displayed a type-2 binding spectrum with dimethylsulfoxide or 2-butanol. No such spectrum was found with the saline controls. These properties are similar to those which are observed with microsomes from chronic ethanol-fed rats. These similarities suggest the possibility that pyrazole treatment may induce a cytochrome P-450 isozyme with properties similar to the ethanol-inducible cytochrome P-450.