Epigallocatechin-3-gallate pretreatment alleviated doxorubicin-induced ferroptosis and cardiotoxicity in vitro and in vivo by upregulating AMPKα2 and activating adaptive autophagy.
Does epigallocatechin-3-gallate pretreatment prevent doxorubicin-induced cardiotoxicity and ferroptosis in in vitro and in vivo models?
Epigallocatechin-3-gallate pretreatment protects against doxorubicin-induced cardiotoxicity by reducing ferroptosis through AMPKα2-mediated adaptive autophagy in preclinical models.
Reports indicate that the mechanism of doxorubicin (Dox)-induced cardiotoxicity is very complex, involving multiple regulatory cell death forms. Furthermore, the clinical intervention effect is not ideal. Iron dependence, abnormal lipid metabolism, and excess reactive oxygen species generation, three characteristics of ferroptosis, are potential therapeutic intervention targets. Here, we confirmed in vitro and in vivo that at least autophagy, apoptosis, and ferroptosis are involved in Dox cardiotoxicity-induced damage. When the neonatal rat cardiomyocytes and H9C2 cells or C57BL/6 mice were subjected to Dox-induced cardiotoxicity, epigallocatechin-3-gallate pretreatment could effectively decrease iron accumulation, inhibit oxidative stress and abnormal lipid metabolism, and thereby alleviate Dox cardiotoxicity-induced ferroptosis and protect the myocardium according to multiple functional, enzymatic, and morphological indices. The underlying mechanism was verified to involve the upregulation and activation of AMP-activated protein kinase α2, which promoted adaptive autophagy, increased energy supply, and maintained mitochondrial function. We believe that epigallocatechin-3-gallate is a candidate phytochemical against Dox-induced cardiotoxicity.
He et al. (Wed,) conducted a other in Doxorubicin-induced cardiotoxicity. Epigallocatechin-3-gallate pretreatment vs. Doxorubicin alone was evaluated on Doxorubicin cardiotoxicity-induced ferroptosis and myocardial damage. Epigallocatechin-3-gallate pretreatment alleviated doxorubicin-induced ferroptosis and cardiotoxicity in vitro and in vivo by upregulating AMPKα2 and activating adaptive autophagy.