Inhibition of Oxidative Stress in Renal Ischemia-Reperfusion Injury.
Superoxide, nitric oxide (NO), and peroxynitrite are important mediators in the pathogenesis of ischemia-reperfusion (I/R) injury. We tested the renoprotective effects of allopurinol (ALP), a xanthine oxidase inhibitor, N-nitro-L-arginine methyl ester (L-NAME), and 5,10,15,20-tetrakis (N-methyl-4-pyridyl) porphyrinato iron (III) (FeTMPyP) by selective inhibition of superoxide, NO, and peroxynitrite, respectively.



Male Sprague-Dawley rats were randomly assigned to 5 groups (n = 6 per group). Group 1 was a sham-operated group. Group 2 was the renal I/R group (30-minute ischemia followed by 24-hour reperfusion). Rats in groups 3, 4, and 5 received ALP, L-NAME, or FeTMPyP, respectively, at 5 minutes before the reperfusion. Serum creatinine (Cr), blood urea nitrogen (BUN), renal tissue malondialdehyde, superoxide dismutase, histological changes, apoptosis, and monocyte infiltration were evaluated. In addition, the combined treatment with ALP and L-NAME was compared with FeTMPyP in a second independent experiment.



The administration of ALP, L-NAME, and FeTMPyP diminished the increase in Cr (P = .0066 for all) and BUN (P = .0066 for ALP; and P = .013 for L-NAME) induced by I/R injury and decreased the histological damage (P = .0066 for all). In addition, ALP, L-NAME, and FeTMPyP attenuated the oxidative stress response as determined by a decrease in malondialdehyde level (P = .0066 for all), apoptotic renal tubular cells (P = .0066 for all), and monocyte infiltration (P = .0066 for all). The combined treatment of ALP and L-NAME decreased Cr and BUN levels to a greater degree than FeTMPyP (P = .016 for Cr; P = .0079 for BUN).



Superoxide, NO, and peroxynitrite are involved in renal I/R injury. The reduction of peroxynitrite formation, via inhibition of superoxide or NO, or the induction of peroxynitrite decomposition may be beneficial in renal I/R injury.
From the *Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Daegu, Korea; and †Department of Anesthesiology and Pain Medicine, Yeungnam University College of Medicine, Daegu, Korea.
Eun Kyung
EK
Choi
Hoon
H
Jung
Kyung Hwa
KH
Kwak
Soo Jin
SJ
Yi
Jung A
JA
Lim
Sol Hee
SH
Park
Jun-Mo
JM
Park
Sioh
S
Kim
Dae-Lim
DL
Jee
Dong Gun
DG
Lim
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D019610:Cytoprotection; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D030421:Peroxynitrous Acid / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013481:Superoxides / Q000378:metabolism; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
C492721:5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato-iron(III); D000975:Antioxidants; D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D000493:Allopurinol; D003404:Creatinine; D019001:Nitric Oxide Synthase; D014969:Xanthine Oxidase; D019331:NG-Nitroarginine Methyl Ester