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

doi:10.1186/s13619-023-00170-x

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

School of Life Science and Health

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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.

Original language	English
Article number	25
Journal	Cell Regeneration
Volume	12
Issue number	1
DOIs	https://doi.org/10.1186/s13619-023-00170-x
State	Published - Dec 2023

Keywords

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

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10.1186/s13619-023-00170-x

Cite this

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title = "Chemical screening links disulfiram with cardiac protection after ischemic injury",

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",

author = "Yuanyuan Chen and Jianyong Du and Lixia Zheng and Zihao Wang and Zongwang Zhang and Zhengyuan Wu and Xiaojun Zhu and Xiong, \{Jing Wei\}",

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doi = "10.1186/s13619-023-00170-x",

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AU - Chen, Yuanyuan

AU - Du, Jianyong

AU - Zheng, Lixia

AU - Wang, Zihao

AU - Zhang, Zongwang

AU - Wu, Zhengyuan

AU - Zhu, Xiaojun

AU - Xiong, Jing Wei

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

KW - Disulfiram

KW - Gasdermin D

KW - High-throughput chemical screening

KW - Ischemia/reperfusion injury

KW - Rat cardiomyocytes

KW - Small molecule

UR - https://www.scopus.com/pages/publications/85165368734

U2 - 10.1186/s13619-023-00170-x

DO - 10.1186/s13619-023-00170-x

M3 - 文章

AN - SCOPUS:85165368734

SN - 2045-9769

VL - 12

JO - Cell Regeneration

JF - Cell Regeneration

IS - 1

M1 - 25

ER -

Chemical screening links disulfiram with cardiac protection after ischemic injury

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