Some effects of selenium deficiency on the hepatic microsomal cytochrome P-450 system in the rat

Abstract

The hepatic microsomal cytochrome P-450 system was investigated in male rats fed a selenium-deficient Torula yeast diet for 3 mo after weaning and in control rats fed the same diet with 0.5 μg selenium as Na 2SeO 3 added per gram of diet. Cytochrome P-450 and b 5 contents, NADPH-cytochrome c reductase, ethylmorphine demethylase, 2- and 4-biphenyl hydroxylase activities, and pentobarbital sleeping time were measured and the effect of phenobarbital pretreatment on these parameters was determined. The effect of 3-methylcholanthrene pretreatment on all parameters except sleeping time was studied. Selenium deficiency caused no alterations in any of the above activities in untreated or 3-methylcholanthrene-treated rats. However, phenobarbital treatment in seleniumdeficient rats produced an increase in cytochrome P-450 content of only 70% as compared to 150% in the similarly treated controls. The induction of ethylmorphine demethylase activity by phenobarbital was also impaired in selenium-deficient rats. No such impairment in the induction of cytochrome b 5 content, NADPH-cytochrome c reductase activity, biphenyl hydroxylase activity, or pentobarbital sleeping time occurred. The percentage of the carbon monoxide-reactive cytochrome P-450 which bound metyrapone was the same in phenobarbital-treated selenium-deficient rats and in phenobarbital-treated controls. Also the cytochrome P-450 ethyl isocyanide binding spectra were similar in phenobarbital-treated selenium-deficient rats and in phenobarbital-treated control rats. These data indicate a specific effect of selenium in the hepatic microsomal cytochrome P-450 system. The biochemical function of selenium giving rise to this effect is unknown.