The 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.