title: Adaptive changes in hepatic glutathione metabolism in response to excess selenium in rats.
abstract: Experiments were conducted with rats to determine if administration of excess selenium (Se) alters hepatic glutathione (GSH) metabolism. Se was fed, 6 ppm as Na2SeO3, for 6 weeks in a 15% casein, tocopherol-free diet and compared to 0.1 ppm Se. High Se significantly increased the concentrations of hepatic nonprotein sulfhydryls (NPSH) and oxidized glutathione (GSSG) as well as the GSSG:NPSH ratio. Of the NPSH, 94.1 +/- 1.7% was shown to be GSH. Similar increases in NPSH, GSSG and GSSG:NPSH due to high Se were seen when the diet was supplemented with methionine (0.3%) and/or vitamin E (100 IU/kg diet) although methionine independently increased NPSH and GSSG. Hepatic glucose-6-P dehydrogenase, glutathione reductase and gamma-glutamyl-transpeptidase activities were significantly increased by high Se but cysteine dioxygenase activity was unaffected. An i.p. injection of Na2SeO3 (15 mumol Se/kg body weight) significantly increased hepatic GSSG, which was followed by an increase in NPSH(GSH) compared to saline controls. These results indicate that excess Se causes a shift in hepatic GSH toward a more oxidized state. Increases in NPSH(GSH) and in the enzyme activities observed appeared to be adaptive changes initiated in an attempt to maintain a normal GSSG:GSH ratio. Elevated GSSG or the increased GSSG:GSH ratio caused by Se may initiate these adaptations.
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D050558:Cysteine Dioxygenase; D049308:Dioxygenases; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D019803:Glutathione Disulfide; D005980:Glutathione Reductase / Q000378:metabolism; D006128:Growth / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008297:Male; D010105:Oxygenases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D020887:Selenious Acid; D012643:Selenium / Q000008:administration & dosage* / Q000633:toxicity; D013438:Sulfhydryl Compounds / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D013438:Sulfhydryl Compounds; D005954:Glucosephosphate Dehydrogenase; D010105:Oxygenases; D049308:Dioxygenases; D050558:Cysteine Dioxygenase; D005980:Glutathione Reductase; D005723:gamma-Glutamyltransferase; D020887:Selenious Acid; D005978:Glutathione; D012643:Selenium; D019803:Glutathione Disulfide