SEX-RELATED DIFFERENCES IN RAT-LIVER MICROSOMAL-ENZYMES AND THEIR INDUCTION BY DOXAPRAM

The effects of doxapram on the hepatic microsomal mono-oxygenase syste m of male and female rats were investigated. Male and female rats were administered doxapram (10-120 mg kg(-1) day(-1), i.p.) for 4 days. In female rats, administration of doxapram (20, 40, 60, 80, 100 and 120 mg kg(-1)) elevated the parameters in a dose-dependent manner while do xapram (100 and 120 mg kg(-1)) elevated the levels of cytochrome P450 and hexobarbitone hydroxylase in male rats. Doxapram (40 mg kg(-1)) ca used induction of hepatic drug metabolism typified by an increase of h epatic microsomal cytochrome P450 content and activities of hexobarbit one hydroxylase, benzphetamine N-demethylase and ethylmorphine N-demet hylase in female rats, but no change in male rats. These findings were supported by the results of SDS/polyacrylamide-gel electrophoresis. H owever, 7-ethoxycoumarin O-de-ethylase and arylhydrocarbon hydroxylase activities were significantly increased in male rats. NADPH-cytochrom e c reductase and NADH-cytochrome c reductase activities, and cytochro me b(5) content were unaffected in rats of both sexes. The sex-depende nt cytochrome P450 species may be selectively sensitive to the action of doxapram.