In the present study, we investigated possible involvement of N-methyl-D-aspartate receptors (NMDAR) in estradiol mediated protection against ischemia reperfusion (I/R)-induced acute renal failure (ARF) in rats. Bilateral renal ischemia of 40 min followed by reperfusion for 24 h induced ARF in male wistar rats. Quantification of serum creatinine, creatinine clearance (CrCl), blood urea nitrogen (BUN), uric acid, potassium, fractional excretion of sodium (Fe), and urinary microproteins was done to assess I/R-induced renal damage in rats. Oxidative stress in kidneys was measured in terms of myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels. Hematoxylin & eosin and periodic acid Schiff stains were used to reveal structural changes in renal tissues. Estradiol benzoate (0.5 and 1.0 mg/kg, intraperitoneally, i.p.) was administered 1 h prior to I/R in rats. In separate groups, rats were treated with NMDAR agonists, glutamic acid (200 mg/kg, i.p.), and spermidine (20 mg/kg, i.p.) before administration of estradiol. Marked increase in serum creatinine, BUN, uric acid, serum potassium, Fe, microproteinuria, and reduction in CrCl demonstrated I/R-induced ARF in rats. Treatment with estradiol mitigated I/R-induced changes in serum/urine parameters. Moreover, estrogen attenuated oxidative stress and structural changes in renal tissues. Prior administration of glutamic acid and spermidine abolished estradiol mediated renoprotection in rats. These results indicate the involvement of NMDAR in estradiol mediated renoprotective effect. In conclusion, we suggest that NMDAR antagonism serves as one of the mechanisms in estradiol-mediated protection against I/R-induced ARF in rats.
