Glutathione catabolism by the ischemic rat kidney

• Published in: American journal of physiology. Renal physiology Vol. 258; no. 6; pp. F1546 - F1553
• Main Authors: Slusser, S O, Grotyohann, L W, Martin, L F, Scaduto, Jr, R C
• Format: Journal Article
• Language: English
• Published: United States 01.06.1990
• Subjects: Acetylcysteine - pharmacology; Animals; Antimetabolites - pharmacology; Cysteine - metabolism; gamma-Glutamyltransferase - antagonists & inhibitors; Glutathione - metabolism; Ischemia - metabolism; Isoxazoles - pharmacology; Kidney - blood supply; Kidney - metabolism; Male; Rats; Reperfusion; Sulfhydryl Compounds - metabolism
• ISSN: 0002-9513; 1931-857X; 2163-5773; 1522-1466
• DOI: 10.1152/ajprenal.1990.258.6.f1547

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 pool 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 gamma-glutamyltransferase (gamma-GT), although the degree of suppression was small in comparison to the extent of gamma-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.