The glutathione (GSH) content of rat kidney decreases after cessation of blood flow, falling to 40% of control levels 35 min after renal artery occlusion [R. C. Scaduto, Jr., V. H. Gattone II, L. W. Grotyohann, J. Wertz, and L. F. Martin. Am. J. Physiol. 255 (Renal Fluid Electrolyte Physiol. 24): F911-F921, 1988]. Renal GSH levels remained depressed for at least 2 h after resumption of blood flow. Because GSH functions in the removal of free radicals, and lipid peroxidation is a free radical-initiated process that occurs in the ischemic kidney, we investigated the fate of this GSH poól in the ischemic kidney. Using high-performance liquid chromatography to measure thiols, we found the loss of GSH to be associated with a stoichiometric accumulation of cysteine in the kidney. Moreover, preischemic labeling of the renal GSH pool with 35S led to accumulation of [35S]cysteine during ischemia that had the same specific activity as that of tissue GSH. Formation of cysteine during ischemia was suppressed in rats pretreated with acivicin, an inhibitor of γglutamyltransferase (γ-GT), although the degree of suppression was small in comparison to the extent of γ-GT inhibition. During the initial 2 min of blood reflow after ischemia, tissue cysteine returned to control levels, and a transient increase in the cysteine content of renal venous blood was observed. After ischemia, renal GSH levels remained depressed, but postischemic GSH levels could be increased by administration of N-acetylcysteine during the ischemic period. We conclude that renal ischemia leads to marked catabolism of GSH to cysteine, which is flushed from the tissue upon resumption of renal blood flow. The data are consistent with a pathway involving initial hydrolysis of GSH by γ-GT under conditions in which GSH synthesis is suppressed. Resynthesis of GSH after ischemia is limited by the availability of cysteine.
|Original language||English (US)|
|Journal||American Journal of Physiology - Renal Fluid and Electrolyte Physiology|
|Issue number||6 27-6|
|State||Published - 1990|
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