The effect of melatonin on capecitabine-induced cardiac toxicity in rats

Background Capecitabine (CAP), a fluoropyrimidine, can display cardiotoxic features, which may lead to life-threatening conditions. Melatonin (MLT), a tryptophan-derived neurohormone that, in addition to its antioxidant properties, is known for its anti-apoptotic and anti-inflammatory properties as well. The purpose of the current study was to examine the effect of MLT on CAP-induced cardiotoxicity. Methods and materials A total of 25 male Wistar rats were divided into 5 groups; the control, MLT10 (daily intraperitoneal (i.p.) injections of 10 mg/kg MLT), CAP500 (weekly i.p. injection of 500 mg/kg CAP), CAP+MLT5, and CAP+MLT10, all of them treated for 6 weeks. Different serological, biochemical, and histopathological assays were performed to assess the study’s aim. Moreover, a rat myocardium (H9C2(2–1)) cell line was also used to assess this protective effect in-vitro. Results The use of CAP resulted in significant cardiotoxicity, which was indicated by elevated levels of malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), as well as serological markers such as CK-MB and LDH. CAP administration also led to a decrease in body weight, total antioxidant capacity (TAC), and glutathione peroxidase (GPx) levels. Furthermore, CAP disrupted various ECG parameters, including an increased ST-segment elevation, elongated QRS complex, and prolonged QTc duration. Histological examination revealed hyperemia, necrosis, and hyalinization of cardiac tissue as a result of CAP exposure. However, treatment with MLT demonstrated beneficial effects. MLT treatment attenuated oxidative stress, reduced levels of cardiac enzymes, and ameliorated histopathological degenerations. MLT also alleviated ECG abnormalities and increased GPx and TAC levels. Additionally, MLT administration helped restore body weight that was lost as a result of CAP exposure. The MTT results showed that MLT was beneficial for rats treated with CAP in a dose-dependent manner. Conclusion Our findings indicated that the administration of MLT in rats significantly enhanced the cardiac toxicity induced by CAP.