Differential effects of dietary selenium on hepatic and renal glutathione-related enzymes and on hepatic microsomal drug metabolism in the rat.
These studies were undertaken to assess the effect of dietary selenium on glutathione-related enzyme activities in the liver and kidney and on hepatic drug metabolism. The intent was to study underlying mechanisms of selenium-induced beneficial effects in some models of hepatoxicity and carcinogenesis. Dietary selenium, as sodium selenite, was incorporated into a torula yeast basal diet (0.02 ppm selenium) and fed to male rats at supplementation levels of 0.0-5.0 ppm selenium for periods of three or six weeks. Additionally, a commercial cereal-based diet (CD, 0.05-0.08 ppm selenium) was compared to the experimentally defined diet (DD) supplemented with approximately the same amount of selenium. Liver and kidney glutathione peroxidase activity essentially plateaued at levels of selenium of 0.1 ppm and greater. CD- and DD-fed animals had hepatic and renal glutathione peroxidase activities which were similar. Glutathione S-transferase activity in liver, but not kidney, increased with increasing supplements of selenium. Glutathione S-transferase activities in CD- and DD-fed rats were not different. Cytochrome P-450 content and associated oxidative drug metabolism activities were relatively unmodified by selenium. Overall, dietary selenium appeared to act by enhancing potential conjugative detoxication pathway, rather than by decreasing the potential activation of chemicals via the hepatic cytochrome P-450 system.
Department of Pharmacodynamics and Toxicology, University of Nebraska Medical Center, Omaha.
M H
MH
Davies
B A
BA
Merrick
D F
DF
Birt
R C
RC
Schnell
D000818:Animals; D003600:Cytosol / Q000378:metabolism; D004032:Diet; D004912:Erythrocytes / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000494:pharmacology*
D004364:Pharmaceutical Preparations; D006899:Mixed Function Oxygenases; D005978:Glutathione; D012643:Selenium