EFFECTS OF ACUTE GLUTATHIONE DEPLETION INDUCED BY L-BUTHIONINE-(S,R)-SULFOXIMINE ON RAT-LIVER GLUCOSE-6-PHOSPHATASE ACTIVITY

The effect of acute glutathione (GSH) depletion induced by GSH-depleti ng agent L-buthionine-(S,R)-sulfoximine (BSO) on hepatic microsomal gl ucose-6-phosphatase (G6Pase) activity in male Wistar rats was investig ated. Liver GSH evaluated in highperformance liquid chromatography aft er administration of 4 mmol.Kg(-1) BSO i.p. was decreased by 19% and 5 0% at the time-points of 1.5 h and 3 h, respectively. In these conditi ons, a significant decrease in V-max and an increasing trend in K-m of hepatic G6Pase activity were observed, especially in 3 h BSO-rats. Al terations in kinetic parameters of G6Pase were calculated in both inta ct and detergent-treated microsomes, using glucose-6-phosphate and pyr ophosphate as substrate. A little increase in thiobarbituric acid-reac tive substances and a limited decrease in 5,5'-dithiobis(2-nitrobenzoa te)-reactive protein thiols were also noted. The results of this study show that acute GSH depletion induced by BSO is able to affect hepati c microsomal G6Pase activity. A possible explanation to account for th e effect of BSO-induced GSH depletion on hepatic G6Pase system is disc ussed.