Dexmedetomidine inhibits ferroptosis through the Akt/GSK3β/Nrf2 axis and alleviates adriamycin-induced cardiotoxicity.

The cardiotoxicity of Adriamycin(ADR) limits its clinical application, and its molecular mechanism is not very clear. At present, Dexrazoxane (DXZ) is the only approved drug to prevent ADR-induced cardiotoxicity (DIC), but it also has serious adverse reactions. Therefore, it is a key scientific challenge to find a drug with strong myocardial protection, few adverse reactions and no effect on the anti-tumor effect of ADR. In this study, we established the DIC model in rats. Cardiomyocyte hypertrophy and myocardial fibrosis increased significantly, and MDA and LDH increased significantly in serum. Dexmedetomidine (DEX) is a carbohydrate with multiple biological activities that can significantly improve the above DIC process. Echocardiography confirmed that DEX could reverse the changes of ESV, EDV, EF and FS induced by ADR. In vitro, experiments confirmed that DEX reversed the upregulation of ANP, BNP, MHC and Collagen III protein levels induced by ADR. DEX improves DIC by inhibiting ferroptosis. Erastin, a ferroptosis agonist, confirmed that DEX improved DIC by inhibiting ferroptosis. Mechanically, DEX increases the expression of Nrf2 in the nucleus through the Akt/Gsk3β signalling axis, thereby regulating ferroptosis in cardiomyocytes. In addition, DEX can improve DIC while not affecting the anti-tumor effect of ADR.