Chemical screening links disulfiram with cardiac protection after ischemic injury

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-appro...

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Detalles Bibliográficos
Autores principales: Chen, Yuanyuan, Du, Jianyong, Zheng, Lixia, Wang, Zihao, Zhang, Zongwang, Wu, Zhengyuan, Zhu, Xiaojun, Xiong, Jing-Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Nature Singapore 2023
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10356704/
https://www.ncbi.nlm.nih.gov/pubmed/37466803
http://dx.doi.org/10.1186/s13619-023-00170-x
Descripción
Sumario: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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13619-023-00170-x.

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