2. Academic Validation
  3. Chemical screening links disulfiram with cardiac protection after ischemic injury

Chemical screening links disulfiram with cardiac protection after ischemic injury

  • Cell Regen. 2023 Jul 19;12(1):25. doi: 10.1186/s13619-023-00170-x.
Yuanyuan Chen 1,  Jianyong Du 2,  Lixia Zheng 1,  Zihao Wang 1,  Zongwang Zhang 1,  Zhengyuan Wu 3,  Xiaojun Zhu 1,  Jing-Wei Xiong 4 5
Affiliations

Affiliations

  • 1 Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100871, China.
  • 2 School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, 266071, China.
  • 3 PKU-Nanjing Institute of Translational Medicine, Nanjing, 211800, China.
  • 4 Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100871, China. jingwei_xiong@pku.edu.cn.
  • 5 PKU-Nanjing Institute of Translational Medicine, Nanjing, 211800, China. jingwei_xiong@pku.edu.cn.
PMID: 37466803 DOI: 10.1186/s13619-023-00170-x
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 H2O2-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.

Keywords

Disulfiram; Gasdermin D; High-throughput chemical screening; Ischemia/reperfusion injury; Rat cardiomyocytes; Small molecule.

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