Effect of aurothioglucose on glutathione and glutathione-metabolizing and related enzymes in rat liver and kidney.
The antirheumatic drug aurothioglucose is an inhibitor of the selenoenzyme GSH peroxidase. During chrysotherapy, the decreased levels of erythrocyte GSH and serum sulfhydryls of rheumatoid arthritis patients are normalized concomitant with clinical efficacy. This investigation examined the in vivo and in vitro effect of gold(I) as aurothioglucose on enzymes related to the GSH redox cycle or metabolism. The enzymes measured were GSH peroxidase, GSSG reductase, gamma-glutamyl transpeptidase, gamma-glutamylcysteine synthetase, GSH S-transferase, GSH thiotransferase, glucose-6-phosphate dehydrogenase, superoxide dismutase and catalase. Rats were injected with 30 mumol aurothioglucose/kg body wt. daily for 7 days by intramuscular injection. GSH levels in aurothioglucose-treated rats were 68% higher in erythrocytes (P less than 0.005) and 45% higher in kidney (P less than 0.001) than in control rats. Treatment with aurothioglucose did not elevate plasma or liver GSH. The enzyme activities that were changed by aurothioglucose treatment were GSH peroxidase in kidney (41% decreased, P = 0.005) and liver (13% decreased, P less than 0.05), gamma-glutamyl transpeptidase in kidney (15% decreased, P less than 0.05), and catalase in kidney (58% decreased, P less than 0.001). Kidney glucose-6-phosphate dehydrogenase activity was increased 50% (P less than 0.005) and GSH S-transferase was increased 72% (P less than 0.001). In vitro the only liver enzymes inhibited more than 50% by concentrations of less than 50 microM aurothioglucose were GSH peroxidase (50% inhibited by 25 microM aurothioglucose) and GSH thiotransferase (50% inhibited by 5 microM aurothioglucose). Studies of in vitro enzyme inhibition by aurothioglucose could not be used to predict decreased enzyme activities in vivo. Although decreased activities of two major enzymes that utilize GSH, GSH peroxidase and gamma-glutamyl transpeptidase, coincided with elevated GSH in kidneys of aurothioglucose-treated rats, a direct cause and effect relationship remains speculative.
D000818:Animals; D006051:Aurothioglucose / Q000494:pharmacology*; D005978:Glutathione / Q000032:analysis* / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000032:analysis; D005982:Glutathione Transferase / Q000032:analysis; D006046:Gold / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000172:deficiency
D008054:Lipid Peroxides; D006051:Aurothioglucose; D006046:Gold; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D005978:Glutathione; D012643:Selenium