Journal
JOURNAL OF SURGICAL RESEARCH
Volume 178, Issue 1, Pages E25-E34Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jss.2012.02.022
Keywords
Leukocyte-endothelial interaction; Lipid peroxidation; Intercellular adhesion molecule-1; Male rats; Myeloperoxidase; Nitrite/nitrate; P-selectin; Renal ischemia-reperfusion; Injury; Tumor necrosis factor-alpha; Zafirlukast
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Funding
- Scientific Research, College of Medicine Research Center (CMRC), King Saud University
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Background: Renal inflammation has an important role in the development of ischemia-reperfusion injury of the kidney. Cysteinyl leukotrienes have been implicated in many inflammatory conditions. The aim of this study was to investigate the ability of the cysteinyl leukotriene receptor blocker, zafirlukast, to alleviate renal dysfunction and injury in a rat model of renal ischemia-reperfusion injury. Methods: We induced renal ischemia for 45 min, followed by 24 h reperfusion. We gave zafirlukast at a dose of 20 mg/kg/d for 3 d before ischemia-reperfusion. At the end of the reperfusion (24 h), we collected blood samples to measure blood urea nitrogen, creatinine, tumor necrosis factor-alpha, intercellular adhesion molecule-1, and nitrite/nitrate. We took kidney samples for histological and immunohistochemical assessment, and to measure malondialdehyde, glutathione content, and myeloperoxidase activity. Results: Induction of renal ischemia-reperfusion resulted into renal dysfunction, as indicated by elevated levels of blood urea nitrogen and serum creatinine, serum nitrite and nitrate, serum tumor necrosis factor-a, and intercellular adhesion molecule-1. An oxidative stress marker, renal malondialdehyde concentration, was increased, whereas renal reduced glutathione content was decreased. Myeloperoxidase activity, suggestive of neutrophil infiltration, was elevated in renal tissues. Histological changes confirmed these biochemical changes, as did P-selectin overexpression in renal tissues subjected to ischemia-reperfusion. Administration of zafirlukast before ischemia-reperfusion improved renal functions and reduced serum levels of nitrite and nitrate, tumor necrosis factor-a, and intercellular adhesion molecule-1, renal concentration of myeloperoxidase activity, and malondialdehyde concentration, whereas increased renal reduced glutathione concentration. Moreover, zafirlukast reduced histopathological features of tubular injury and P-selectin overexpression in both cortex and medulla. Conclusions: These results demonstrate that zafirlukast significantly reduces the severity of ischemic acute renal failure, probably via anti-inflammatory action, reduction of neutrophil infiltration into renal tissues, and oxidative stress subsequent to an attenuation of P-selectin expression. (C) 2012 Elsevier Inc. All rights reserved.
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