Elevation of renal glutathione enhances ischemic injury.
In a previous study, we tested the hypothesis that an elevated level of renal glutathione (GSH) would protect the kidney from ischemic injury. However, prior elevation of GSH with GSH monoethylester enhanced then injury induced by 35 min of ischemia and blood reflow [Scaduto RC Jr, Gattone VH, Grotyohann LW, et al; Effect of an altered glutathione content on renal ischemic injury. Am J Physiol 1988;255:F911-F921]. Additionally, GSH monoethylester produced morphologic alterations in the absence of ischemia. Thus the greater ischemic injury observed after GSH ester pretreatment could have been due to a synergistic effect between the events caused by ischemia and the pretreatment. The present study was conducted to evaluate the utility of elevating renal GSH levels by administration of GSH. Administration of GSH (1 mmol/kg body weight) caused a 3-fold elevation of renal GSH levels and a 6-fold elevation of renal cysteine levels after 60 min without causing changes in renal morphology or GFR. After 35 min of renal artery occlusion and 90 min of blood reflow, animals pretreated with GSH had a much greater decline in GFR than untreated control animals. This enhancement of renal ischemic injury in GSH-treated animals was similar to that observed following administration of GSH monoethylester. We conclude that administration of GSH is the method of choice for elevation of renal GSH and that elevation of renal GSH leads to an enhanced ischemia-induced injury which is independent of the method employed to elevate renal GSH.
Scaduto
R C
RC
Department of Surgery, Milton S. Hershey Medical Center, Hershey, Pa.
Gattone
V H
VH
Martin
L F
LF
Yang
H C
HC
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001783:Blood Flow Velocity; D003545:Cysteine / Q000032:analysis* / Q000378:metabolism; D005919:Glomerular Filtration Rate; D005978:Glutathione / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D007275:Injections, Intravenous; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000227:Adenine Nucleotides; D005978:Glutathione; D003545:Cysteine