Chemical screening links disulfiram with cardiac protection after ischemic injury
Yuanyuan Chen, Jianyong Du, Lixia Zheng, Zihao Wang, Zongwang Zhang, Zhengyuan Wu, Xiaojun Zhu, Jing‐Wei Xiong
Abstract
Abstract Ischemia–reperfusion injury occurs after reperfusion treatment for patients suffering myocardial infarction, however the underlying mechanisms are incompletely understood and effective pharmacological interventions are limited. Here, we report the identification and characterization of the FDA-approved drug disulfiram (DSF) as a cardioprotective compound. By applying high-throughput chemical screening, we found that DSF decreased H 2 O 2 -induced cardiomyocyte death by inhibiting Gasdermin D, but not ALDH1, in cardiomyocytes. Oral gavage of DSF decreased myocardial infarct size and improved heart function after myocardial ischemia–reperfusion injury in rats. Therefore, this work reveals DSF as a potential therapeutic compound for the treatment of ischemic heart disease.