Chatterjee, P.K., Todorovic, Z., Sivarajah, A., Mota-Filipe, H., Brown, P.A.J., Stewart, K.N., Mazzon, E., Cuzzocrea, S. and Thiemermann, C. (2005) Inhibitors of calpain activation (PD150606 and E-64) and renal ischemia-reperfusion injury Biochemical Pharmacology, 69 (7). pp. 1121-1131. ISSN 0006-2952Full text not available from this repository.
Calpain activation has been implicated in the development of ischemia-reperfusion (I-R) injury. Here we investigate the effects of two inhibitors of calpain activity, PD150606 and E-64, on the renal dysfunction and injury caused by I-R of rat kidneys in vivo. Male Wistar rats were administered PD150606 or E-64 (3 mg/kg i.p.) or vehicle (10%, v/v, DMSO) 30 min prior to I-R. Rats were subjected to bilateral renal ischemia (45 min) followed by reperfusion (6 h). Serum and urinary biochemical indicators of renal dysfunction and injury were measured; serum creatinine (for glomerular dysfunction), fractional excretion of Na+ (FENa, for tubular dysfunction) and urinary N-acetyl-β-d-glucosaminidase (NAG, for tubular injury). Additionally, kidney tissues were used for histological analysis of renal injury, immunohistochemical analysis of intercellular adhesion molecule-1 (ICAM-1) expression and nitrotyrosine formation. Renal myeloperoxidase (MPO) activity (for polymorphonuclear leukocyte infiltration) and malondialdehyde (MDA) levels (for tissue lipid peroxidation) were determined. Both PD150606 and E-64 significantly reduced the increases in serum creatinine, FENa and NAG caused by renal I-R, indicating attenuation of renal dysfunction and injury and reduced histological evidence of renal damage caused by I-R. Both PD150606 and E-64 markedly reduced the evidence of oxidative stress (ICAM-1 expression, MPO activity, MDA levels) and nitrosative stress (nitrotyrosine formation) in rat kidneys subjected to I-R. These findings provide the first evidence that calpain inhibitors can reduce the renal dysfunction and injury caused by I-R of the kidney and may be useful in enhancing the tolerance of the kidney against renal injury associated with aortovascular surgery or renal transplantation.
|Item Type:||Journal article|
|Uncontrolled Keywords:||Renal/kidney; Ischemia; Reperfusion-injury; Calpain inhibitor; PD150606; E-64|
|Subjects:||B000 Health Professions > B200 Pharmacology Toxicology and Pharmacy|
|DOI (a stable link to the resource):||10.1016/j.bcp.2005.01.003|
|Faculties:||Faculty of Science and Engineering > School of Pharmacy and Biomolecular Sciences|
|Depositing User:||editor spbs|
|Date Deposited:||08 Nov 2007|
|Last Modified:||05 Jun 2013 11:21|
Actions (login required)
Downloads per month over past year