Chatterjee, P.K., Brown, P.A.J., Cuzzocrea, S., Zacharowski, K., Stewart, K.N., Mota-Filipe, H., McDonald, M.C. and Thiemermann, C. (2001) Calpain inhibitor-1 reduces renal ischemia/reperfusion injury in the rat Kidney International, 59 (6). pp. 2073-2083. ISSN 0085-2538Full text not available from this repository.
Background Activation of the cysteine protease calpain has been implicated in renal ischemia/reperfusion (I/R) injury. The aim of this study was to investigate the effects of calpain inhibitor-1 (Cal I-1) in an in vivo model of renal I/R injury. Methods Male Wistar rats were administered Cal I-1 (10 mg/kg, IP) 30 minutes before undergoing bilateral renal ischemia (45 minutes) followed by reperfusion (6 hours). Plasma concentrations of urea, creatinine, Na+, gamma-glutamyl transferase (gammaGT), aspartate aminotransferase (AST) and urinary Na+, glutathione S-transferase (GST), and N-acetyl-beta-D-glucosaminidase (NAG) were measured for the assessment of renal dysfunction and I/R injury. Creatinine clearance (CCr) and fractional excretion of Na+ (FENa) were used as indicators of glomerular and tubular function, respectively. Kidney myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were measured for assessment of neutrophil infiltration and lipid peroxidation, respectively. Renal sections were used for histologic grading of renal injury and for immunohistochemical localization of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Results Cal I-1 significantly reduced I/R-mediated increases in urea, creatinine, gammaGT, AST, NAG, and FENa and significantly improved CCr. Cal I-1 also significantly reduced kidney MPO activity and MDA levels. Cal I-1 also reduced histologic evidence of I/R-mediated renal damage and caused a substantial reduction in the expression of iNOS and COX-2, both of which involve activation of nuclear factor-kappaB (NF-kappaB). Conclusions These results suggest that Cal I-1 reduces the renal dysfunction and injury associated with I/R of the kidney. We suggest that the mechanism could involve the inhibition of I/R-mediated activation of NF-kappaB.
|Item Type:||Journal article|
|Uncontrolled Keywords:||kidney injury; inducible nitric oxide synthase; COX-2; nuclear factor-kappaB; acute renal failure|
|Subjects:||B000 Health Professions > B200 Pharmacology Toxicology and Pharmacy|
|DOI (a stable link to the resource):||10.1046/j.1523-1755.2001.00722.x|
|Faculties:||Faculty of Science and Engineering > School of Pharmacy and Biomolecular Sciences|
|Depositing User:||editor spbs|
|Date Deposited:||08 Oct 2007|
|Last Modified:||20 Mar 2014 15:53|
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