Plasma glutathione and glutathione disulfide in the rat: regulation and response to oxidative stress.
Plasma GSH and GSSG concentrations were examined after the administration of compounds that deplete intracellular GSH either by adduct formation or by production of oxidative stress. A modified assay based on the GSSG reductase method was developed that minimizes the artifactual auto-oxidation of GSH to GSSG and mixed disulfides by rapid addition of bis(3-carboxy-4-nitrophenyl)disulfide or N-ethylmaleimide directly to whole blood or tissue samples. Control arterial plasma GSH and GSSG concentrations were found to be 16.5 +/- 0.7 and 0.3 +/- 0.1 microM, respectively. Depletion of GSH by fasting or by the administration of acetaminophen or diethyl maleate was associated with a proportional decrease in the arterial plasma GSH concentrations (r = 0.94) consistent with the hypothesis that the liver in vivo is a major source of plasma GSH. Diquat and t-butyl hydroperoxide, but not acetaminophen or diethyl maleate, elicited large increases in arterial plasma GSSG concentrations (17- and 115-fold, respectively) and several-fold increases in biliary GSSG levels without markedly increasing hepatic GSSG levels (2.7- and 1.2-fold, respectively). In contrast, treatment with paraquat produced substantial increases in arterial plasma GSSG levels (22-fold) without large increases in the bile (3-fold). Assessment of the arteriovenous difference for GSSG across the lungs after paraquat administration demonstrated that the lung may be a significant source of plasma GSSG. In conclusion, plasma GSH concentrations appear to reflect mainly intrahepatic GSH concentration, whereas plasma GSSG appears to arise from both hepatic and extrahepatic sites.(ABSTRACT TRUNCATED AT 250 WORDS)
D000082:Acetaminophen / Q000494:pharmacology; D000818:Animals; D004178:Diquat / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000097:blood* / Q000378:metabolism; D019803:Glutathione Disulfide; D008658:Inactivation, Metabolic; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008298:Maleates / Q000494:pharmacology; D010269:Paraquat / Q000494:pharmacology; D010545:Peroxides / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D020122:tert-Butylhydroperoxide
D008298:Maleates; D010545:Peroxides; D000082:Acetaminophen; D020122:tert-Butylhydroperoxide; D004178:Diquat; C014476:diethyl maleate; D005978:Glutathione; D010269:Paraquat; D019803:Glutathione Disulfide