TY - JOUR
T1 - Inhibition of Oxidative Stress in Renal Ischemia-Reperfusion Injury
AU - Choi, Eun Kyung
AU - Jung, Hoon
AU - Kwak, Kyung Hwa
AU - Yi, Soo Jin
AU - Lim, Jung A.
AU - Park, Sol Hee
AU - Park, Jun Mo
AU - Kim, Sioh
AU - Jee, Dae Lim
AU - Lim, Dong Gun
N1 - Publisher Copyright:
Copyright © 2016 International Anesthesia Research Society.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84986220659&partnerID=8YFLogxK
U2 - 10.1213/ANE.0000000000001565
DO - 10.1213/ANE.0000000000001565
M3 - Article
C2 - 27607480
AN - SCOPUS:84986220659
SN - 0003-2999
VL - 124
SP - 204
EP - 213
JO - Anesthesia and Analgesia
JF - Anesthesia and Analgesia
IS - 1
ER -