Harpagoside Protects Against Doxorubicin-Induced Cardiotoxicity via P53-Parkin-Mediated Mitophagy.

ABSTRACT: Doxorubicin (DOX) is one of the most effective chemotherapeutic agents. However, its clinical use is limited due to the severe risk of cardiotoxicity. One of the hallmarks of doxorubicin-induced cardiotoxicity (DICT) is the cascade of mitophagy deficiency-mitochondrial oxidative injury-apoptosis, while so far, there is no preventive strategy for alleviating DICT by targeting this molecular mechanism. Excitedly, based on our previous drug screen in DICT zebrafish model, harpagoside (HAR) showed dramatic anti-DICT efficacy superior to dexrazoxane (DXZ) only cardioprotectant approved by FDA. Therefore, its pharmacological effects and molecular mechanism on DICT mouse and rat cardiomyocytes were further discussed. In vivo, HAR significantly improved cardiac function and myocardial struc

SUBMITTER: Li W 

PROVIDER: S-EPMC8867983 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature