Gossypol Acetic Acid Attenuates Cardiac Ischemia/Reperfusion Injury in Rats via an Antiferroptotic Mechanism

Myocardial ischemia/reperfusion (I/R) injury has been associated with ferroptosis, which is characterized by an iron-dependent accumulation of lipid peroxide to lethal levels. Gossypol acetic acid (GAA), a natural product taken from the seeds of cotton plants, prevents oxidative stress. However, the...

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Autores principales:	Jian-Hong Lin, Kun-Ta Yang, Pei-Ching Ting, Yu-Po Luo, Ding-Jyun Lin, Yi-Shun Wang, Jui-Chih Chang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ferroptosis myocardial ischemia/reperfusion injury gossypol acetic acid glutathione peroxidase 4 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/53a83b3206134e23b4bab5be056fd9f7
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spelling	oai:doaj.org-article:53a83b3206134e23b4bab5be056fd9f72021-11-25T16:53:33ZGossypol Acetic Acid Attenuates Cardiac Ischemia/Reperfusion Injury in Rats via an Antiferroptotic Mechanism10.3390/biom111116672218-273Xhttps://doaj.org/article/53a83b3206134e23b4bab5be056fd9f72021-11-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1667https://doaj.org/toc/2218-273XMyocardial ischemia/reperfusion (I/R) injury has been associated with ferroptosis, which is characterized by an iron-dependent accumulation of lipid peroxide to lethal levels. Gossypol acetic acid (GAA), a natural product taken from the seeds of cotton plants, prevents oxidative stress. However, the effects of GAA on myocardial I/R-induced ferroptosis remain unclear. This study investigated the ability of GAA to attenuate I/R-induced ferroptosis in cardiomyocytes along with the underlying mechanisms in a well-established rat model of myocardial I/R and isolated neonatal rat cardiomyocytes. H9c2 cells and cardiomyocytes were treated with the ferroptosis inducers erastin, RSL3, and Fe-SP. GAA could protect H9c2 cells against ferroptotic cell death caused by these ferroptosis inducers by decreasing the production of malondialdehyde and reactive oxygen species, chelating iron content, and downregulating mRNA levels of <i>Ptgs2</i>. GAA could prevent oxygen-glucose deprivation/reperfusion-induced cell death and lipid peroxidation in the cardiomyocytes. Moreover, GAA significantly attenuated myocardial infarct size, reduced lipid peroxidation, decreased the mRNA levels of the ferroptosis markers <i>Ptgs2</i> and <i>Acsl4</i>, decreased the protein levels of ACSL4 and NRF2, and increased the protein levels of GPX4 in I/R-induced ex vivo rat hearts. Thus, GAA may play a cytoprotectant role in ferroptosis-induced cardiomyocyte death and myocardial I/R-induced ferroptotic cell death.Jian-Hong LinKun-Ta YangPei-Ching TingYu-Po LuoDing-Jyun LinYi-Shun WangJui-Chih ChangMDPI AGarticleferroptosismyocardial ischemia/reperfusion injurygossypol acetic acidglutathione peroxidase 4MicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1667, p 1667 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ferroptosis myocardial ischemia/reperfusion injury gossypol acetic acid glutathione peroxidase 4 Microbiology QR1-502
spellingShingle	ferroptosis myocardial ischemia/reperfusion injury gossypol acetic acid glutathione peroxidase 4 Microbiology QR1-502 Jian-Hong Lin Kun-Ta Yang Pei-Ching Ting Yu-Po Luo Ding-Jyun Lin Yi-Shun Wang Jui-Chih Chang Gossypol Acetic Acid Attenuates Cardiac Ischemia/Reperfusion Injury in Rats via an Antiferroptotic Mechanism
description	Myocardial ischemia/reperfusion (I/R) injury has been associated with ferroptosis, which is characterized by an iron-dependent accumulation of lipid peroxide to lethal levels. Gossypol acetic acid (GAA), a natural product taken from the seeds of cotton plants, prevents oxidative stress. However, the effects of GAA on myocardial I/R-induced ferroptosis remain unclear. This study investigated the ability of GAA to attenuate I/R-induced ferroptosis in cardiomyocytes along with the underlying mechanisms in a well-established rat model of myocardial I/R and isolated neonatal rat cardiomyocytes. H9c2 cells and cardiomyocytes were treated with the ferroptosis inducers erastin, RSL3, and Fe-SP. GAA could protect H9c2 cells against ferroptotic cell death caused by these ferroptosis inducers by decreasing the production of malondialdehyde and reactive oxygen species, chelating iron content, and downregulating mRNA levels of <i>Ptgs2</i>. GAA could prevent oxygen-glucose deprivation/reperfusion-induced cell death and lipid peroxidation in the cardiomyocytes. Moreover, GAA significantly attenuated myocardial infarct size, reduced lipid peroxidation, decreased the mRNA levels of the ferroptosis markers <i>Ptgs2</i> and <i>Acsl4</i>, decreased the protein levels of ACSL4 and NRF2, and increased the protein levels of GPX4 in I/R-induced ex vivo rat hearts. Thus, GAA may play a cytoprotectant role in ferroptosis-induced cardiomyocyte death and myocardial I/R-induced ferroptotic cell death.
format	article
author	Jian-Hong Lin Kun-Ta Yang Pei-Ching Ting Yu-Po Luo Ding-Jyun Lin Yi-Shun Wang Jui-Chih Chang
author_facet	Jian-Hong Lin Kun-Ta Yang Pei-Ching Ting Yu-Po Luo Ding-Jyun Lin Yi-Shun Wang Jui-Chih Chang
author_sort	Jian-Hong Lin
title	Gossypol Acetic Acid Attenuates Cardiac Ischemia/Reperfusion Injury in Rats via an Antiferroptotic Mechanism
title_short	Gossypol Acetic Acid Attenuates Cardiac Ischemia/Reperfusion Injury in Rats via an Antiferroptotic Mechanism
title_full	Gossypol Acetic Acid Attenuates Cardiac Ischemia/Reperfusion Injury in Rats via an Antiferroptotic Mechanism
title_fullStr	Gossypol Acetic Acid Attenuates Cardiac Ischemia/Reperfusion Injury in Rats via an Antiferroptotic Mechanism
title_full_unstemmed	Gossypol Acetic Acid Attenuates Cardiac Ischemia/Reperfusion Injury in Rats via an Antiferroptotic Mechanism
title_sort	gossypol acetic acid attenuates cardiac ischemia/reperfusion injury in rats via an antiferroptotic mechanism
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/53a83b3206134e23b4bab5be056fd9f7
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Gossypol Acetic Acid Attenuates Cardiac Ischemia/Reperfusion Injury in Rats via an Antiferroptotic Mechanism

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