Melatonin Ameliorates 5-Fluorouracil-Induced Cytotoxicity and Apoptosis in H9c2 Cell Line: Insights into Cytoprotection and Anti-Apoptotic Mechanisms.

Cardiotoxicity represents a significant adverse effect associated with 5-fluorouracil (5-FU), a widely used chemotherapeutic agent. Melatonin (MLT), a powerful antioxidant and agent that prevents apoptosis, has shown promise in mitigating various toxicities. This study evaluated the cardioprotective effect of MLT on 5-FU-induced cardiotoxicity (5-FU-IC) in the H9c2 cardiomyoblast cell line. The cells were grown in DMEM + FBS and divided into four groups: control (untreated), 5-FU-treated (varying concentrations for 48 hours), MLT-treated (varying concentrations), and 5-FU plus MLT-treated (combined treatment for 48 hours). The cell viability was evaluated using the MTT assay, while apoptosis was analyzed through flow cytometry following Annexin V staining and caspase-3/7 (Cas-3/7) activity assays. Treatment with 5-FU led to a significant decrease in the viability of H9c2 cells in a dose-dependent fashion, with an estimated IC50 value of 400 μM. Co-treatment with MLT at 100 and 200 μM significantly enhanced cell viability and reduced apoptosis induced by 5-FU, as demonstrated by flow Cytometry and reduced Cas-3/7 activity. These results emphasize the protective effects of MLT against 5-FU-IC, primarily through its anti-apoptotic mechanisms. These findings underscore the importance of MLT to protect against 5-FU-IC through its anti-apoptotic properties. MLT shows promise as a cardioprotective agent in mitigating 5-FU-IC, providing perspectives on its potential therapeutic application in mitigating cardiac risks linked to chemotherapy.