Agomelatine on cisplatin-induced nephrotoxicity via oxidative stress and apoptosis

Abstract

Drug-induced nephrotoxicity is the greatest deterrent to the use of cisplatin, which is a frequently used chemotherapeutic with proven efectiveness in cancer therapy. Agomelatine, which is used in the treatment of sleep disorders and depression, has gained attention in recent years with its antioxidative and anti-infammatory efects. In this study, the efects of the synthetic melatonin agonist agomelatine on nephrotoxicity were investigated in a rat model of cisplatin-induced nephrotoxicity using biochemical, histological, and immunohistochemical methods. Thirty-two male rats were divided into 4 groups: 1. control group, 2. agomelatine group, 3. cisplatin group, 4. cisplatin+agomelatine group. In the cisplatin group, there were widespread atypical glomerular structures and vacuolization in tubular epithelial cells, necrotic tubules, deterioration of brush border structure in proximal tubules, and fbrotic areas characterized by difuse polymorphonuclear leukocyte (PNL) and extensive collagen deposition in the interstitial spaces. However, in the cisplatin+agomelatine group, we observed a reduction in glomeruli of atypical structure and necrotic tubules, in PNL infltration in interstitial spaces, and fbrotic areas compared to the cisplatin group. The cisplatin+agomelatine group showed lower malondialdehyde (MDA) serum creatinine, serum urea levels, and higher glutathione (GSH) levels compared to the cisplatin group. Immunohistochemical analyses revealed that the elevated NF-kβ/p65, 8-OHdG, and cleaved caspase-3 positivity in the cisplatin group had signifcantly decreased in the cisplatin+agomelatine group. In conclusion, agomelatine showed a nephroprotective efect against cisplatin-induced nephrotoxicity.