Embryonic stem cell-derived cardiomyocytes as a model system to study cardioprotective effects of dexamethasone in doxorubicin cardiotoxicity

Embryonic stem cell (ESC)-derived beating cardiomyocytes may be considered as a suitable model for in vitro assessment of pharmacological and toxicological studies. In this model, laboratory animals are not required. In addition, physiological functions, such as heart beat, are assessed rather than single parameters such as cell viability. Here we report that doxorubicin (DOX) cardiotoxicity on mouse ESC-derived beating cardiomyocytes can be ameliorated by treatment with dexamethasone (DEX) when DEX is administrated only before DOX and not in combination with DOX. DEX effect appears to be mediated via glucocorticoid receptor and increases cardiomyocyte-specific gene expression. Cardiotoxicity of DOX can be augmented by calcium channel blocker, verapamil (VER) which also decreases the expression of cardiac gene markers. This model provides us with a clinical suggestion which proposes that the beneficial effect of DEX is obtained when DEX was added before DOX administration.