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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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
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author Chen, Yuanyuan
Du, Jianyong
Zheng, Lixia
Wang, Zihao
Zhang, Zongwang
Wu, Zhengyuan
Zhu, Xiaojun
Xiong, Jing-Wei
author_facet Chen, Yuanyuan
Du, Jianyong
Zheng, Lixia
Wang, Zihao
Zhang, Zongwang
Wu, Zhengyuan
Zhu, Xiaojun
Xiong, Jing-Wei
author_sort Chen, Yuanyuan
collection PubMed
description 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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spelling pubmed-103567042023-07-21 Chemical screening links disulfiram with cardiac protection after ischemic injury Chen, Yuanyuan Du, Jianyong Zheng, Lixia Wang, Zihao Zhang, Zongwang Wu, Zhengyuan Zhu, Xiaojun Xiong, Jing-Wei Cell Regen Research Article 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. Springer Nature Singapore 2023-07-19 /pmc/articles/PMC10356704/ /pubmed/37466803 http://dx.doi.org/10.1186/s13619-023-00170-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Chen, Yuanyuan
Du, Jianyong
Zheng, Lixia
Wang, Zihao
Zhang, Zongwang
Wu, Zhengyuan
Zhu, Xiaojun
Xiong, Jing-Wei
Chemical screening links disulfiram with cardiac protection after ischemic injury
title Chemical screening links disulfiram with cardiac protection after ischemic injury
title_full Chemical screening links disulfiram with cardiac protection after ischemic injury
title_fullStr Chemical screening links disulfiram with cardiac protection after ischemic injury
title_full_unstemmed Chemical screening links disulfiram with cardiac protection after ischemic injury
title_short Chemical screening links disulfiram with cardiac protection after ischemic injury
title_sort chemical screening links disulfiram with cardiac protection after ischemic injury
topic Research Article
url 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
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