Does metformin reduce oxidative stress, apoptosis, and mitochondrial dysfunction in human cardiac myocyte cells exposed to 5-fluorouracil?
Metformin demonstrates therapeutic potential against 5-fluorouracil-induced cardiotoxicity in vitro by reducing oxidative stress, apoptosis, and mitochondrial dysfunction.
BACKGROUND: 5-Fluorouracil (5-FU) is a chemotherapeutic agent used primarily to treat various cancers. While it has been successful in improving cancer survival rates, 5-FU is also known to be cardiotoxic. Treatment options for patients experiencing 5-FU-induced cardiotoxicity are limited to standard heart failure medications. OBJECTIVES: This study aims to investigate how metformin can reduce oxidative stress, apoptosis, and mitochondrial dysfunction in human cardiac myocyte (HCM) cells. METHODS: The optimal doses of 5-FU were determined using the MTT assay. Following exposure to 5-FU, HCM cells were treated with metformin for 48 h. The study measured the levels of reactive oxygen species (ROS), glutathione (GSH), and the activity of superoxide dismutase (SOD). Additionally, cytochrome c release and mitochondrial membrane potential were assessed in HCM cells. The expression levels of BAX and Bcl-2 were also examined, along with the activity of Caspase-3. RESULTS: The findings indicated that 5-FU significantly increased ROS levels, decreased GSH levels, and reduced SOD activity-effects that were mitigated by metformin. Furthermore, 5-FU markedly increased apoptosis and induced mitochondrial dysfunction, both of which were significantly reduced by metformin in a dose-dependent manner in HCM cells. CONCLUSION: According to the present study results, metformin, through a reduction in oxidative stress, apoptosis, and mitochondrial malfunction, can have therapeutic potential in HCM cells toxicity induced by 5-FU.
Alreshidi et al. (2026) studied this question.