Aurothioglucose effect on sulfhydryls and glutathione-metabolizing enzymes: in vivo inhibition of selenium-dependent glutathione peroxidase.
Fisher 344 rats injected with a total of 20.8 +/- 1.5 mg of gold (Au) as aurothioglucose over an 8-wk period were used to study the effect of long-term Au treatment on selenium-dependent glutathione peroxidase (SeGSHPx), other enzymes related to GSH metabolism, GSH, nonprotein sulfhydryls, and total sulfhydryls (SH) in various tissues. The indirect coupled assay for SeGSHPx revealed decreased activity in platelets of Au-treated rats but not in other tissues. Inhibition of SeGSHPx by Au is reversible upon dilution. A direct assay of GSH consumption by concentrated tissue cytosols that was developed to minimize enzyme dilution provided evidence of in vivo inhibition of SeGSHPx in kidney and liver from Au-injected rats. Kidneys of these rats had decreased (P less than 0.05) activities of GSSG reductase (36%), gamma-glutamylcysteine synthetase (19%), and gamma-glutamyl transpeptidase (26%), and increased (P less than 0.05) activities of glucose 6-phosphate dehydrogenase (90%) and GSH S-transferase (130%). The reactivity of fresh plasma SH groups with 5,5'-dithiobis-(2-nitrobenzoic acid) increased as a function of injection time. Enhanced SH reactivity suggests that Au may react with protein GSH-disulfides to release GSH. New findings were (i) decreased platelet SeGSHPx and kidney GSSG reductase in aurothioglucose-injected rats, (ii) direct in vivo inhibition of kidney and liver SeGSHPx in aurothioglucose-injected rats, and (iii) no significant correlation between the activity of GSH-metabolizing enzymes and levels of tissue GSH.
D000818:Animals; D006051:Aurothioglucose / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors; D006046:Gold / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012643:Selenium / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D013438:Sulfhydryl Compounds; D006051:Aurothioglucose; D006046:Gold; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D005978:Glutathione; D012643:Selenium