{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T03:57:29Z","timestamp":1788235049963,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:00:00Z","timestamp":1636502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Buddhist Tzu Chi General Hospital","award":["TCRD 110-60"],"award-info":[{"award-number":["TCRD 110-60"]}]},{"name":"Tzu Chi Medical Foundation","award":["TCMF-MP 108-01-02"],"award-info":[{"award-number":["TCMF-MP 108-01-02"]}]},{"name":"Chi-Tsung Cheng donated to Buddhist Tzu Chi General Hospital","award":["IMAR-109-01-03"],"award-info":[{"award-number":["IMAR-109-01-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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 Ptgs2. 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 Ptgs2 and Acsl4, 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.<\/jats:p>","DOI":"10.3390\/biom11111667","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T09:19:21Z","timestamp":1636535961000},"page":"1667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Gossypol Acetic Acid Attenuates Cardiac Ischemia\/Reperfusion Injury in Rats via an Antiferroptotic Mechanism"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3011-8259","authenticated-orcid":false,"given":"Jian-Hong","family":"Lin","sequence":"first","affiliation":[{"name":"Division of Experimental Surgery, Department of Surgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 707, Sec. 3, Zhongyang Rd., Hualien 97002, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun-Ta","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Tzu Chi University, No. 701, Sec. 3, Zhongyang Rd., Hualien 97004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Ching","family":"Ting","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 707, Sec. 3, Zhongyang Rd., Hualien 97002, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Po","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 707, Sec. 3, Zhongyang Rd., Hualien 97002, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding-Jyun","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Medicine, Tzu Chi University, No. 701, Sec. 3, Zhongyang Rd., Hualien 97004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Shun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Tzu Chi University, No. 701, Sec. 3, Zhongyang Rd., Hualien 97004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jui-Chih","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 707, Sec. 3, Zhongyang Rd., Hualien 97002, Taiwan"},{"name":"Department of Surgery, School of Medicine, Tzu Chi University, No. 701, Sec. 3, Zhongyang Rd., Hualien 97004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105466","DOI":"10.1016\/j.phrs.2021.105466","article-title":"Ferroptosis and its emerging roles in cardiovascular diseases","volume":"166","author":"Li","year":"2021","journal-title":"Pharmacol. 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