Induction of selenium-glutathione peroxidase by stimulation of metabolic hydrogen peroxide production in vivo

Abstract

Selenium-glutathione peroxidase (Se-GPx) provides a major detoxication pathway for hydrogen peroxide produced in the cytosolic and mitochondrial compartments of rat liver. The aim of this study was to assess the influence of an increase in N-demethylase (cytochrome P 450-dependent) or monoamine oxidase (MAO) activity on Se-GPx biosynthesis in vivo. Male Sprague-Dawley rats injected i.p. with ethylmorphine (60 mg/kg in physiological saline, twice a day) exhibited an increase in hepatic Se-GPx activity from the second day of intoxication, with a maximal increase of approximately 2-fold after 4 days, whereas a similar introxication with β-phenylethylamine (50 mg/kg) did not induce liver Se-GPx in spite of a long-lasting malonaldehyde overproduction. Ethylmorphine did not induce liver catalase. No induction of Se-GPx was observed in females injected with ethylmorphine. When compared with males, such females have a 2- to 3-fold higher hepatic Se-GPx activity, and they do not exhibit a marked diurnal cycle of hepatic GSH concentration as males do. A decrease in hepatic GSH concentration was observed after the second daily injection of ethylmorphine in both males and females, but this decrease was more pronounced and prolonged in females. Our observations are consistent with stimulation of Se-GPx biosynthesis in male rat liver by a cytochrome P 450-dependent, but not by an MAO-dependent H 2O 2 production in vivo. In females, a major pathway for ethylmorphine hepatic detoxication is glutathione-dependent, but may not involve coupling of N-demethylase and Se-GPx activities.