Document Type : Original Article
Authors
1
Student Research Committee, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
2
Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
3
Pharmaceutical Sciences Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
4
Mobility Impairment Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
Abstract
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.
Keywords: Melatonin, 5-Fluorouracil, Apoptosis, Cardiotoxicity, Chemotherapy, H9c2
cells.
Keywords