Evaluation of metformin's effect on 5-fluorouracil-induced cardiotoxicity through cellular protection

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.

This study aims to investigate how metformin can reduce oxidative stress, apoptosis, and mitochondrial dysfunction in human cardiac myocyte (HCM) cells.

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.

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.

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.