Humanin Analogue (HNG) Enhances the Protective Effect of Dexrazoxane against Doxorubicin-induced Cardiotoxicity

The chemotherapeutic effect of Doxorubicin (Dox) is limited by cumulative dose-dependent cardiotoxicity in cancer survivors. Dexrazoxane (DRZ) is approved to prevent Dox-induced cardiotoxicity. Humanin and its synthetic analog HNG have cytoprotective effect on the heart. To investigate the cardioprotective efficacy of HNG alone or in combination with DRZ against Dox-induced cardiotoxicity, eighty adult male mice were randomly divided into 8 groups to receive the following treatments via intraperitoneal injection: saline daily; HNG (5mg/kg) daily; DRZ (60mg/kg) weekly; Dox (3mg/kg) weekly; DRZ+HNG, Dox+HNG; Dox+DRZ and Dox+HNG+DRZ. Echocardiogram was performed before and at 4, 8 and 9.5 weeks after beginning of treatment. All mice were euthanized at 10 weeks. In the absence of Dox, HNG, DRZ or DRZ+HNG had no adverse effect on the heart. Dox treatment caused decreases in ejection fraction and cardiac mass, and increases in cardiomyocyte apoptosis and intracardiac fibrosis. HNG or DRZ alone blunted the Dox-i...