Dose-Dependent Protective Effect of Ivabradine against Ischemia-Reperfusion-Induced Renal Injury in Rats

Abstract

Background/Aims: This study was designed to investigate the dose-dependent protective effect of ivabradine, a specific inhibitor of the cardiac sinoatrial node, on renal ischemia-reperfusion (I/R) injury in rats. Methods: Rats were divided into six groups: group 1, control; group 2, I/R (60 min ischemia followed by 24 h reperfusion); groups 3 and 4, 0.6–6 mg/kg ivabradine; and groups 5 and 6, sham+0.6–6 mg/kg ivabradine. At the end of the study, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase contents were assayed in the kidney tissues; serum blood levels of urea nitrogen (BUN), creatinine (Cr) and albumin also were determined. Results: Tissue MDA levels were found to be significantly higher in the I/R group, whereas SOD and CAT levels were lower when compared to the control group. Ivabradine (0.6 mg/kg) treatment reduced the MDA levels and elevated the SOD and CAT enzyme activity. Treatment with a dose of 6 mg/kg ivabradine further increased MDA levels and did not ameliorate SOD or CAT activities. Serum levels of BUN and Cr were significantly higher in the I/R group. I/R+0.6 mg ivabradine reduced the elevated BUN and Cr levels. Conclusion: This study indicates that ivabradine exerts a dose-dependent response beyond heart rate reduction against renal I/R injury.