Glycine Exerts Renal Antioxidant Effects and Restores Hemodynamic Alterations in Rats Treated with Diclofenac Sodium: Roles of Renal Angiotensin Converting Enzyme, Angiotensin II Receptor and Mineralocortocoid Receptor

Abstract

Diclofenac (DIC) is known to alter renal function in the form of hemodynamically-mediated acute renal failure. This study 
evaluated the protective role of the amino acid, glycine (Gly) on nephrotoxicity and acute hemodynamic alterations induced by
DIC (9 mg/kg) in male Wistar rats. The rats were divided into four groups (n=7/group) including Group A (control); Group B 
(DIC-treated), Groups C (DIC + Gly1, 250 mg/kg) and Group D (DIC + Gly2 500 mg/kg). Systolic (SBP), diastolic (DBP) and 
mean arterial (MAP) blood pressures were significantly (p<0.05) reduced in rats treated with DIC alone, compared to control. 
Kidneys from DIC-treated rats showed altered histology with significantly (p<0.05) increased hydrogen peroxide (H2O2), 
malondialdehyde (MDA) and protein carbonyl contents, but decreased glutathione (GSH) glutathione peroxidase (GPx), 
glutathione S-transferase (GST) and superoxide dismutase (SOD) activities. Immunohistochemistry revealed down-regulation of 
renal angiotensin converting enzyme (ACE), but increased expressions of angiotensin type II receptor (AT2R) and 
mineralocorticoid receptor (MR) in DIC-treated rats. However, pre-treatment with Gly reversed most of the aforementioned 
effects of DIC. The present results suggest that oral glycine protected kidney tissues and restored DIC-induced hemodynamic 
changes by modifying renal expression of the renin-angiotensin-mineralocortocoid pathway and/or renal oxidative stress.