Inhibition of Hepatic Mixed-Function Oxidase Enzymes in Mice by Acute and Chronic Treatment with Selenium

Abstract

The effect of selenium administered acutely or chronically on the hepatic microsomal drugmetabolizing system has been investigated in mice. After 72 h following acute administration of selenium (7.5 mg/kg, i.p.), there was a significant inhibition of the activities of aminopyrine (AM) N-demethylase and ethylmorphine (EM) N-demethylase, and cytochrome P-450 levels but no change in the activities of aniline (AN) hydroxylase, 7-ethoxycoumarin (EC) O-deerhylase, reduced nicotinamide adenine dinucleotide phoshate (NADPH)-cytochrome c reductase a nd reduced nicotinamide adenine dinucleotide (NADH)-ferricyanide reductase, and cytochrome b5 content. Chronic administration of selenium in the drinking water (1 or 2 ppm selenium) for 12 weeks, resulted in no alteration in any of the parameters measured. However, significant decreases in activities of AM N-demethylase and AN hydr oxylase, and cytochrome P-450 levels were detected in animals given higher doses of selenium (4 or 8 ppm selenium). Follwoing the in vitro additions of selenium 10 hepatic microsomes obtained from untreated mice, selenium inhibited the AM N-demcthytuse, AN hydroxylase and 7-EC O-dcethylase in a concentration-dependent manner, but no alteration in NADPH-cytochrome c reductase and cytochrome P-450 levels was observed. These results indicate that selenium is a specific from inhibitor of hepatic monooxygenase. © 1992, The Pharmaceutical Society of Japan. All rights reserved.