Inhibition of Oxidative Stress in Renal Ischemia-Reperfusion Injury

Eun Kyung Choi, Hoon Jung, Kyung Hwa Kwak, Soo Jin Yi, Jung A. Lim, Sol Hee Park, Jun Mo Park, Sioh Kim, Dae Lim Jee, Dong Gun Lim

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Original languageEnglish
Pages (from-to)204-213
Number of pages10
JournalAnesthesia and Analgesia
Volume124
Issue number1
DOIs
StatePublished - 1 Jan 2017

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