Alleviation of the mitochondrial dynamics impairment in doxorubicin-induced cardiomyocyte toxicity by cardioprotective agents

Purpose The cardiotoxic effects of anti-cancer agents on cardiomyocytes are a significant challenge for physicians. The current experiment aims to explore the potential cardioprotective effects of cardiovascular agents, i.e., eplerenone, empagliflozin, and colchicine by restoring mitochondrial fusion, reducing fission and mitigating the severity of fibrosis in doxorubicin-treated H9c2 cells. Materials and Methods The viability of H9c2 cells are assessed using the MTT assay. Additionally, the underlying mechanisms in H9c2 cells subject to treatment with eplerenone, empagliflozin, colchicine and doxorubicin were explored through a combination of techniques, including fluorescence microscopy, siRNA transfection, flow cytometry, and western blot analysis. Results After exposure to doxorubicin, H9c2 cells exhibit a decrease of mitochondrial fusion, an increase in myocardial fibrosis, and perturbed mitochondrial fission. However, treatment with these cardiovascular agents have effectively counteracted these doxorubicin-induced alterations with the restoration of mitochondrial dynamics and the alleviation myocardial fibrosis. Conclusion This study suggests that eplerenone, empagliflozin, and colchicine possess direct cytoprotective actions in an in vitro model of H9c2 cells with the potential to serve as therapeutic agents of doxorubicin-induced myocardial fibrosis.