Effect of simvastatin on renal function and impairment following to the unilateral urethral obstruction in rat

Obstructive uropathy indicates any possible obstruction in urinary flow. At the end stage, obstruction cause changes in the renal function. Competitive HMG-CoA reductase inhibitors, like simvastatin, decrease serum lipid level. It is shown that statines have organ protective effects following different impairments. The aim of this study was the evaluation of simvastatin effect on renal function and impairment following unilateral urethral obstruction in rat. In this experimental study 50 adult male rats (Sprague-Dawley), subjected to unilateral urethral obstruction (UUO), were divided randomly into five groups including control, UUO, UUO/SIM (simvastatin), Sham-operated and sham/SIM group. The control group received the drug solvent for 15 days. In UUO group, animals received the drug solvent postoperatively. Animals in UUO/SIM group received simvastatin (2 mg/kg/twice a day) for 15 days (starting one day before operation). Sham and sham/SIM groups were subjected to surgery without urethral obstruction. Blood samples were collected on day 0, 3, 7 and 14 after surgery to measure creatinine, urea and cholesterol levels of the serum. Rats were sacrificed for histopathological evaluation on day 14. Using one-way ANOVA analysis, Tukey's post hoc and student t-test, data were analyzed. The evaluation of biochemical parameters showed that, compared to control the group, the level of creatinine, urea and cholesterol in the UUO group were significantly increased 7 and 14 day postoperative (P<0.05). However, these parameters were decreased in the simvastatin group (P<0.05). Histopathological evaluation showed renal interstitial fibrosis, tubular epithelial necrosis, interstitial infiltration of mononuclear cells, periglomerular sclerosis, subcapsular fibrosis and glomerulosclerosis in the UUO group. Simvastatin administration during urethral obstruction in the UUO/SIM group declined the obstruction induced urethral lesions and the changes of interstitial tissue. There was no significant difference between the control and sham groups. Our findings showed that the urethral obstruction decreased renal function and caused severe impairment in renal tissue. Simvastatin decreased the tissue lesions induced by the obstruction of urethra. Of course, the protective effects of simvastatin in humans need more research.