Elucidation of Molecular Mechanism Involved in Nephroprotective Potential of Naringin in Ethylene Glycol-Induced Urolithiasis in Experimental Uninephrectomized Hypertensive Rats

The objective of present investigation was to evaluate the nephroprotective potential of naringin against ethylene glycol (EG)-induced urolithiasis in experimental uninephrectomized hypertensive rats. EG (0.75% in drinking water) was used to induce urolithiasis in uninephrectomized hypertensive rats. Rats were treated with either naringin (20, 40, and 80 mg/kg, p.o.) for 28 days. Chronic administration of EG resulted in significant alterations (p < 0.05) in serum and urinary parameters (urea nitrogen, uric acid, creatinine, sodium, calcium, and LDH) whereas, administration of naringin (40 and 80 mg/kg) significantly attenuated (p < 0.05) these alterations. Naringin also significantly attenuated (p < 0.05) EG-induced hemodynamic and electrocardiographic abnormalities. Elevated levels of cardiac and renal MDA and nitric oxide and decreased levels of SOD and GSH were significantly restored (p < 0.05) by naringin treatment. RT-PCR analysis revealed that naringin significantly inhibited (p < 0.05) EG-induced upregulated mRNA expressions of renal KIM-1, NGAL, bikunin, and iNOs as well as down-regulated mRNA expressions of eNOs and OPN. Histological aberrations induced in renal and cardiac tissue after chronic administration of EG was significantly decreased (p < 0.05) by naringin. In conclusion, naringin exerts its nephroprotective effect against EG-induced via modulation of elevated oxidative stress and altered renal KIM-1, NGAL, bikunin, iNOs, eNOs, and OPN mRNA expressions.