Glutathione catabolism by the ischemic rat kidney.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Slusser
S O
SO
Department of Surgery, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Grotyohann
L W
LW
Martin
L F
LF
Scaduto
R C
RC
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D003545:Cysteine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism*; D007555:Isoxazoles / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D051381:Rats; D015424:Reperfusion; D013438:Sulfhydryl Compounds / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors
D000963:Antimetabolites; D007555:Isoxazoles; D013438:Sulfhydryl Compounds; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D003545:Cysteine; C006303:acivicin; D000111:Acetylcysteine