• Emanuela Esposito, Stefania Mondello, Rosanna Di Paola, Emanuela Mazzon, Domenico Italiano, Irene Paterniti, Patrizia Mondello, Carmela Aloisi, and Salvatore Cuzzocrea.
• Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) Centro Neurolesi Bonino-Pulejo, Messina, Italy.
• Naunyn Schmiedebergs Arch. Pharmacol. 2011 May 1;383(5):493-508.

AbstractThe aim of this study was to investigate the effects of glutamine in an in vivo rat model of renal ischemia/reperfusion (I/R) injury. Male Wistar rats underwent bilateral renal pedicle clamping for 45 min followed by reperfusion for 6 h. Glutamine (1.5 mg/kg) was administered intraperitoneally (i.p.) 15 min prior to reperfusion. Plasma concentrations of urea, creatinine, γ-glutamyl transferase (γ-GT), and aspartate aminotransferase (AST) were measured for the assessment of renal function and reperfusion injury. Markers of oxidative stress, expression of the pro-inflammatory mediators inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), AT-1 expression, and changes in the oxidative stress-sensitive nuclear factor kappa B (NF-κB) signaling pathway were measured to investigate whether glutamine can reduce the renal dysfunction. Kidney myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were measured for assessment of polymorphonuclear (PMN) cell infiltration and lipid peroxidation, respectively. Renal sections were used for histologic grading of renal injury and for immunohistochemical localization of nitrotyrosine and poly(ADP-ribose) synthetase (PARS). In vivo, glutamine significantly reduced the increase in urea, creatinine, γ-GT, AST, produced by renal ischemia/reperfusion (I/R), suggesting an improvement in both renal function and injury. Glutamine significantly reduced iNOS and NF-κB, kidney MPO activity and MDA levels, indicating a reduction in PMN infiltration and lipid peroxidation, respectively. Glutamine reduced the histological evidence of renal damage associated with I/R and caused a substantial reduction in the staining for nitrotyrosine and PARS, suggesting reduced nitrosative and oxidative stress. Moreover, glutamine attenuated the reduction of COX-2 expression and prevented the increased AT-1 expression after I/R. Our results suggest that glutamine reduces the renal dysfunction and injury associated with I/R of the kidney.

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