Abstract
Four-week-old male Wistar rats were fed a vitamin E (VE) -deficient diet for 8 weeks, followed by intraperitoneal injection of DL-buthionine- [S, R] -sulfoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase, at 1mmol/kg body weight. Rats in glycine (Gly) and/or γ-glutamylcysteine ethyl ester (γ-GC) -treated groups were injected intraperitoneally with Gly and/or γ-GC three times at 0.7mmol/kg body weight in addition to BSO administration. GSH depletion by BSO administration was accompanied by a decrease in the level of renal TBA (2-thiobarbituric acid) and a marked increase in the renal lipofuscin content. γ-GC treatment increased the renal GSH content and inhibited the increase in the renal lipofuscin content. The increase in serum creatinine and the decrease in renal enzyme activities in rats administered BSO were inhibited by γ-GC treatment. γ-GC treatment did not provide complete protection from epithelial necrosis in the proximal renal tubules, but such degeneration in rats treated with γ-GC was observed only in a narrow area of the S3 segment near the descending thin limb of Henle's loop. These results suggest that GSH plays an important role in preventing lipofuscin production through reaction of lipid peroxides with amino acids.
