Nephroprotective effect of coadministration of curcumin and sildenafil in adenine-induced chronic renal failure in rats

Background Chronic renal failure (CRF) is a major public health problem worldwide. The pathophysiological basis of the disease and its complication include inflammation and oxidative stress, which are similar in humans and animals. In this study, we seek to develop new therapeutic modalities for CRF. Objective This study aimed to investigate the nephroprotective effects of curcumin (CUR) and/or sildenafil in adenine (AD) model of CRF. Materials and methods Rats were divided into five groups as follows: control naive group, AD group received AD 200 mg/kg/day orally to induce CRF, CUR group received CUR 200 mg/kg/day in addition to AD, sildenafil group received sildenafil 0.5 mg/kg/day in addition to AD, and combination group received combination of CUR 200 mg/kg/day and sildenafil 0.5 mg/kg/day in addition to AD. After consecutive 28 days of treatment, body weight, kidney index, and Doppler on renal artery assessments were done for all groups. In addition, kidney function tests and markers of oxidative stress were evaluated. Histopathological assessment of renal tissues and immunohistochemical staining for tumor necrosis factor-α were performed. Results CUR, sildenafil, and their combination significantly decreased body weight loss and urine volume and improved renal hemodynamic changes caused by AD. In addition, they significantly improved kidney function tests and biomarkers of oxidative stress. A significant down-regulation of tumor necrosis factor-α immunohistochemical expression was noted. They also brought histopathological changes induced by AD toward normal. Conclusion CUR and sildenafil may play a role in renal protection in AD-induced nephrotoxicity. The combined treatment showed better nephroprotective effect than either treatment alone did.