Inhibition of hepatic mixed-function oxidase enzymes in mice by acute and chronic treatment with selenium.
The effect of selenium administered acutely or chronically on the hepatic microsomal drug-metabolizing 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-deethylase, reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase and 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 hydroxylase, and cytochrome P-450 levels were detected in animals given higher doses of selenium (4 or 8 ppm selenium). Following the in vitro additions of selenium to hepatic microsomes obtained from untreated mice, selenium inhibited the AM N-demethylase, AN hydroxylase and 7-EC O-deethylase 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.
Ishikawa
M
M
Department of Pharmacology and Toxicology, Tohoku College of Pharmacy, Sendai, Japan.
Sasaki
M
M
Koiwai
K
K
Ozaki
M
M
Takayanagi
Y
Y
Sasaki
K
K
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000633:Aminopyrine N-Demethylase / Q000037:antagonists & inhibitors; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D065607:Cytochrome P-450 Enzyme Inhibitors; D015786:Cytochromes b5 / Q000378:metabolism; D005037:Ethylmorphine-N-Demethylase / Q000037:antagonists & inhibitors; D006591:Hexobarbital / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011506:Proteins / Q000032:analysis; D012643:Selenium / Q000633:toxicity*; D012890:Sleep / Q000187:drug effects
D065607:Cytochrome P-450 Enzyme Inhibitors; D011506:Proteins; D015786:Cytochromes b5; D006591:Hexobarbital; D006899:Mixed Function Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase; D005037:Ethylmorphine-N-Demethylase; D009247:NADH, NADPH Oxidoreductases; D012643:Selenium