Glutathione and glutathione ethyl ester supplementation of mice alter glutathione homeostasis during exercise

The present study examined the effect of glutathione (GSH) and glutathione ethyl ester (GSH-E) supplementation on GSH homeostasis and exercise-induced oxidative stress. Male Swiss-Webster mice were randomly divided into 4 gro ups: starved for 24 h and injected with GSH or GSH-E (6 mmol/kg body wt, i. p.) 1 h before exercise, starved for 24 h and injected with saline (S); and having free access to food and injected with saline (C). Half of each grou p of mice was killed either after an acute bout of exhaustive swimming (E) or after rest (R). Plasma GSH concentration was 100-160% (P < 0.05) higher in GSH mice vs. C or S mice at rest, whereas GSH-E injection had no effect. Plasma GSH was not affected by exercise in C or S mice, but was 44 and 34% lower (P < 0.05) in E vs. R mice with GSH or GSH-E injection, respectively . S, GSH- and GSH-E-treated mice had significantly lower liver GSH concentr ation and the GSH:glutathione disulfide (GSSG) ratio than C mice. Hepatic a nd renal GSH and the GSH:GSSG ratio were significantly lower in E vs. R mic e in all groups. GSH-E-treated mice had a significantly smaller exercise-in duced decrease in GSH vs. C, S, and GSH-treated mice and no difference in t he GSH:GSSG ratio in the kidney. Activities of gamma-glutamylcysteine synth etase and gamma-glutamyltranspeptidase in the liver and kidney were not aff ected by either GSH treatment or exercise, GSH concentration and the GSH:GS SG ratio in quadriceps muscle were not different among C, S and GSH-treated mice, but significantly lower in GSH-E-treated mice (P < 0.05). Hepatic ma londialdehyde (MDA) content was greater in exercised mice in all but GSH-E- treated groups. GSH and GSH-E increased MDA levels in the kidney of E vs. R mice, but attenuated exercise-induced lipid peroxidation in muscle. Swim e ndurance time was similar to 2 h longer in GSH (351 +/- 22 min) and GSH-E ( 348 +/- 27) than S mice (237 +/- 17). We conclude that 1) acute GSH and GSH -E supplementation at the given doses does not increase tissue GSH content or redox status; 2) both GSH and GSH-E improve endurance performance and pr event muscle lipid peroxidation during prolonged exercise; and 3) while bot h compounds may impose a metabolic and oxidative stress to the kidney, this side effect is smaller with GSH-E supplementation.