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.

Methotrexate (MTX) is an important drug for rheumatic and non-rheumatic disease therapy. MTX has been associated with many adverse effects ranging from asymptomatic transaminase elevation to fibrotic tissue formation and fatal hepatic necrosis due to oxidative stress. Concerns regarding potential liver toxicity have led to the avoidance of medication, termination, or advice for inquiries in clinical care. The protective and therapeutic effects of a new generation anti-angina drug, ranolazine (RAN), on MTX-induced liver damage were investigated by evaluating its antioxidant mechanism in rats. Thirty-two female Wistar Albino rats were randomly assigned to Control, RAN, prophylaxis, and treatment groups (n=8/group). Liver function enzymes, histopathological assessment and serum biochemical parameters were examined. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) were also measured in liver tissue. MTX administration caused mononuclear inflammation, vascular congestion, ductal proliferation, vacuolization, and fibrosis as evaluated using Roening grading and increases in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase levels ( p<0.05) in the blood, which is compatible with hepatocyte damage in the blood and increased MDA levels in the tissue. Histopathologically, vascular congestion and ductal proliferation, and biochemically, MDA and SOD levels and serum biochemical parameters, significantly decreased in the RAN+MTX and MTX+RAN groups ( p<0.001) when compared with the MTX group. No significant changes were observed in terms of SOD and GSH levels and fibrosis scores in RAN-administered groups ( p>0.05). According to our results, RAN may be a potential hepatoprotective agent against MTX-induced liver injury.