Ranolazine reduces oxidative damage and improves kidney function in cisplatin-induced nephrotoxicity

Abstract

Cisplatin (CIS)-induced nephrotoxicity is associated with oxidative stress, apoptosis, inflammation, and fibrogenesis. In this study, we investigated the therapeutic effects of ranolazine (RAN), a current antianginal drug known to experimentally reduce oxidative damage in CIS-induced nephrotoxicity. We randomly assigned thirty-two Sprague Dawley rats to one of four groups (Control, CIS, CIS+RAN, and RAN+CIS). We evaluated kidney function parameters including blood urea nitrogen (BUN), creatinine (Cre), electrolytes, and albumin, as well as tissue biochemical parameters including malondialdehyde (MDA) and antioxidant enzymes. Histopathological parameters were also assessed. We observed a significant increase in BUN and Cre values in the CIS group compared to the control group (p<0.05). However, there was a significant decrease in BUN values (p<0.05) in the CIS+RAN and RAN+CIS groups compared to the CIS group. In contrast, the decrease in Cre values did not reach statistical significance (p>0.05), and serum electrolytes were comparable among groups. Furthermore, a statistically significant increase in albumin levels was observed in the CIS+RAN group compared to the CIS group (p<0.05). MDA levels were significantly decreased in the CIS+RAN group compared to the CIS group, indicating the antioxidant activity of RAN (p<0.05). Histopathological analysis revealed that necrosis and dilatation in epithelial cells of cortical and medullary tubules were more prominent in the CIS group (p<0.0001). However, in the RAN+CIS group, the histopathological changes observed in the CIS group were found to be significantly reduced (p<0.0001). Degenerative changes in tubules were observed in the CIS+RAN group (p>0.05). Our findings suggest that the beneficial effects of RAN on CIS-induced nephrotoxicity may be related to its antioxidant activity.