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Control rats were orally administrated normal saline. Rats in the second group were orally administrated PE (50\u2009mg\/kg\u2009bw\/once daily) for 4 weeks. Rats in the third group were intraperitoneally injected with DOX (10\u2009mg\/kg on Days 3, 9, 15, and 21 of the experiment). Rats in the fourth group were injected with DOX and PE simultaneously for 4 weeks. DOX significantly augmented the levels of serum heart damage biomarkers. In addition, histopathology indicated that DOX\u2010induced cardiac tissue injury upregulated the expression of fibrogenic factors, alpha smooth muscle actin (\u03b1\u2010SMA), transforming growth factor \u03b21 (TGF\u2010 \u03b21), and p16<jats:sup>INK4A<\/jats:sup>. Downregulation of cell proliferation markers, cyclin\u2010dependent kinase\u20104 (CDK4), and retinoblastoma (Rb) was also observed. Furthermore, DOX\u2010induced oxidative and inflammatory stress resulted in increased cardiac malondialdehyde (MDA), protein carbonyl (PC), interleukin\u20102 (IL\u20102), interleukin\u20106 (IL\u20106), and tumor necrosis factor\u2010alpha (TNF\u2010\u03b1). Decreased cardiac glutathione (GSH) levels and enzyme activity of catalase (CAT), superoxide dismutase (SOD), and glutathione S\u2010transferase (GST) were observed. Treatment of DOX\u2010induced rat cardiotoxicity with PE normalized serum parameters for the aforementioned parameters and alleviated cardiac tissue structure. Furthermore, reduced cardiac tissue \u03b1\u2010SMA and TGF\u2010\u03b21, and increased CDK4 and Rb protein expression, along with the amelioration of oxidative and inflammatory effects were observed. PE attenuates DOX\u2010induced cardiomyocyte inflammation possibly by attenuating the nuclear factor kappa\u2010B (NF\u2010\n<jats:sc>k<\/jats:sc>B) signaling pathway. These results indicate that PE may be useful as a preventative agent against DOX\u2010induced cardiac toxicity.<\/jats:p>","DOI":"10.1002\/jbt.22716","type":"journal-article","created":{"date-parts":[[2021,1,23]],"date-time":"2021-01-23T09:21:16Z","timestamp":1611393676000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Proanthocyanidin alleviates doxorubicin\u2010induced cardiac injury by inhibiting NF\u2010<scp>k<\/scp>B pathway and modulating oxidative stress, cell cycle, and fibrogenesis"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8509-6619","authenticated-orcid":false,"given":"Kadry M.","family":"Sadek","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Veterinary Medicine Damanhour University  Damanhour Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar F. 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