Investigation of the effects of N-acetylcysteine on experimental cisplatin cardiotoxicity

Objective: This thesis aimed to investigate the potential protective effects of N-acetylcysteine against cardiotoxicity induced by cisplatin in an experimental rat model. The study focused on molecular, biochemical, and histopathological aspects. Materials and Methods: A total of 46 male Wistar albino rats were used in the study. The animals were divided into five groups: Control (C, n=8), N-acetylcysteine (NAC, n=8), Cisplatin (CIS, n=10), Cisplatin + N-acetylcysteine (CIS+NAC, n=10), and N-acetylcysteine + Cisplatin (NAC+CIS, n=10). At the end of the experiment, hemodynamic analyses and body weight measurements were performed, and serum samples were analyzed using ELISA to determine levels of Troponin, Myoglobin, and P53. Cardiac tissues were analyzed for MDA and GSH levels, SOD and CAT activities, and gene expression levels of Troponin, Myoglobin, and P53. Additionally, cardiac tissue samples were examined histopathologically using hematoxylin-eosin staining. Results: A significant decrease in body weight was observed in the cisplatin group by the end of the experiment (P < 0.05), while no significant difference was found in the other groups (P > 0.05). The cisplatin group exhibited lower blood pressure and more electrocardiographic abnormalities compared to the other groups. Cardiac tissue MDA levels and CAT activity were significantly increased in all cisplatin-treated groups compared to the Control and NAC groups (P < 0.05). No significant differences were observed among the groups in cardiac tissue GSH and SOD levels or in gene expression levels of Troponin, Myoglobin, and P53 (P > 0.05). Serum P53 protein levels were significantly higher in the cisplatin group than in the other groups (P < 0.05), while there were no statistically significant differences in Troponin and Myoglobin protein levels (P > 0.05). Histopathological examination of the cardiac tissues in the cisplatin groups revealed severe hemorrhage, interstitial edema, and necrotic cardiomyocytes (P < 0.05). Conclusion: The weight loss and abnormalities in cardiac measurements observed following cisplatin administration suggest potential cardiovascular risks. Elevated MDA and CAT levels in cardiac tissue may indicate increased oxidative stress. The reduction of these elevated values by N-acetylcysteine suggests that it may contribute to the regulation of oxidative stress, lipid metabolism, and the glutathione mechanism. Keywords: Cisplatin, N-acetylcysteine, Cardiotoxicity, Rat