Oxidant stress following renal ischemia: changes in the glutathione redox ratio.
Pretreatment of animals with certain antioxidant enzymes and substances decreases renal damage following ischemia and reperfusion. The hypothesis that reoxygenation imposes an oxidant stress has been used to explain this. The present study has directly assessed oxidant stress under these conditions by measuring the glutathione redox ratio ([GSSG/(GSH + GSSG)] x 100) in freeze-clamped kidney. The glutathione peroxidase system plays a role in removing peroxides which result from oxidant stress, generating GSSG from GSH in the process. The selenium-dependent glutathione peroxidase can metabolize H2O2 and other hydroperoxides. A non-selenium-dependent glutathione peroxidase activity is present and can metabolize organic hydroperoxides, but it cannot metabolize H2O2. Under anesthesia, the left renal artery was occluded for 40 minutes and then reflow was allowed. Kidneys were freeze clamped before reflow and after 5, 10, and 15 minutes of reflow. The contralateral kidney was freeze clamped and used as a control. The control value for the glutathione redox ratio was 1.09 +/- 0.05. This fell during ischemia to 0.67 +/- 0.22 and increased significantly to 1.66 +/- 0.29 after five minutes of reperfusion. By 15 minutes it had returned to 1.09 +/- 0.22. Treatment of rats with diquat, which causes a severe oxidant stress, raised the glutathione redox ratio from 0.88 +/- 0.12 to 1.89 +/- 0.15. Thus, reperfusion was concluded to cause a large but transient oxidant stress. Selenium-deficient rats were used to examine the nature of the oxidant stress. Activity of the selenoenzyme glutathione peroxidase was depressed to 2% of control in the kidneys of these rats.(ABSTRACT TRUNCATED AT 250 WORDS)
McCoy
R N
RN
Department of Medicine, University of Texas Health Science Center, San Antonio 78284.
Hill
K E
KE
Ayon
M A
MA
Stein
J H
JH
Burk
R F
RF
D000818:Animals; D002330:Carmustine / Q000009:adverse effects; D004178:Diquat / Q000009:adverse effects; D005978:Glutathione / Q000378:metabolism*; D007511:Ischemia / Q000139:chemically induced / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010084:Oxidation-Reduction; D010545:Peroxides / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000502:physiology
D010545:Peroxides; D008315:Malondialdehyde; D004178:Diquat; D005978:Glutathione; D012643:Selenium; D002330:Carmustine