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Protocatechuic acid (PCA) is a polyphenolic compound with various potent biological activities. In this study, we explored the possible cardioprotective role of PCA against isoproterenol (ISO)\u2010mediated MI. Rats were either injected with ISO (85\u2009mg\/kg, subcutaneously) or pretreated with PCA (100 or 200\u2009mg\/kg, orally). PCA supplementation markedly normalized ISO\u2010induced disturbed cardiac function markers (creatine kinase\u2010MB, lactate dehydrogenase, and troponin T). Notably, PCA administration exerted remarkable increases in glutathione and its derived enzymes, superoxide dismutase, and catalase, as well as decreases in malondialdehyde and nitric oxide levels in the injured cardiac tissue. The molecular findings validated the augmented cellular antioxidative capacity by PCA via increasing the gene expressions of nuclear factor erythroid 2\u2010related factor 2 and heme oxygenase\u20101. The cardioprotective efficacy of PCA extended to suppress cardiac inflammation as demonstrated by the decreased levels of tumor necrosis factor\u2010alpha, interleukin\u20101 beta, and nuclear factor kappa B. Additionally, PCA prevented cardiomyocyte loss and fibrosis by decreasing Bax, caspase\u20103, transforming growth factor\u2010\u03b21 and matrix metalloproteinase\u20109, and enhancing B\u2010cell lymphoma 2 and tissue inhibitors of metalloproteinase\u20103. The cardiac histological screening further confirmed the PCA's protective action. The obtained data recommend PCA as an alternative therapeutic agent to attenuate the molecular, biochemical, and histological alterations associated with MI development.<\/jats:p>","DOI":"10.1002\/jbt.23270","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T05:50:06Z","timestamp":1672725006000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Protocatechuic acid reverses myocardial infarction mediated by \u03b2\u2010adrenergic agonist via regulation of Nrf2\/HO\u20101 pathway, inflammatory, apoptotic, and fibrotic events"],"prefix":"10.1002","volume":"37","author":[{"given":"Li","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cardiology, HenanProvincial Chest Hospital Zhengzhou University  Zhengzhou City Henan Province 450000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Vasculocardiology Xianyang Central Hospital  Xianyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine The Second Affiliated Hospital of Xinxiang Medical College Xinxiang City Henan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chifeng Municipal Hospital  Chifeng City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9290-9972","authenticated-orcid":false,"given":"Bihua","family":"Xia","sequence":"additional","affiliation":[{"name":"The First Department of Cardiology The Second Affiliated Hospital of GuiZhou Medical University Kaili City Guizhou Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan Al","family":"Sberi","sequence":"additional","affiliation":[{"name":"Basic Medical Science, Histopathology Department National Organization for Drug Control and Research Giza Egypt"},{"name":"Department of Biology, Faculty of Science Taif University Taif Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"Elhefny","sequence":"additional","affiliation":[{"name":"Department of Cancer and Molecular Biology, National Cancer Institute Cairo University Cairo Egypt"},{"name":"Department of Medical Genetics, Faculty of Medicine Umm Al\u2010Qura University Alqunfudah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2830-3479","authenticated-orcid":false,"given":"Maha S.","family":"Lokman","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science and Humanities in Al\u2010Kharj Prince Sattam Bin Abdulaziz University  Al\u2010kharj Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami B.","family":"Kassab","sequence":"additional","affiliation":[{"name":"Department of Zoology and Entomology, Faculty of Science Helwan University Cairo Egypt"},{"name":"Department of Biology, Faculty of Science and Arts Al\u2010Baha University  Almakhwah, Al\u2010Baha Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-018-3434-5"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.08.009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2020.153405"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.01043.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3892\/br.2015.500"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms161126040"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111552"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1054\/jcaf.2003.38"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.12.029"},{"issue":"4","key":"e_1_2_9_11_1","first-page":"339","volume":"59","author":"Brooks W. 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