{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T14:43:40Z","timestamp":1773931420390,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Hepatic fibrosis and its progressive form, liver cirrhosis, are dangerously recognized complications of liver injury with limited treatment options. This study evaluated the hepatoprotective effects of ivabradine on thioacetamide (TAA)-induced hepatic fibrosis in rats. Methods: Rats were divided into five groups with 10 rats\/group and treated as follows: normal, where rats received 0.5% CMC-Na solution orally; ivabradine control, where rats received only ivabradine (20 mg\/kg, once daily, orally) for 6 weeks; TAA, where rats received an intraperitoneal (i.p.) injection of TAA (200 mg\/kg) thrice weekly for 6 weeks and daily oral 0.5% CMC-Na solution, and two ivabradine + TAA groups, where two doses of ivabradine were tested. Low (10 mg\/kg) and high (20 mg\/kg) doses of ivabradine were orally given once daily to each group for 6 weeks concurrently with TAA injection. Results: TAA caused marked elevations in liver enzymes, increased MDA, depletion of antioxidant defenses, activation of NF-\u03baB p65 and pro-inflammatory cytokines, dysregulation of apoptotic markers, and upregulation of the PI3K\/AKT\/mTOR and TGF-\u03b2 pathways, accompanied by extensive collagen deposition. Ivabradine produced dose-dependent improvements in biochemical markers of liver function, restored oxidant\/antioxidant balance, suppressed NF-\u03baB p65\/TNF-\u03b1, normalized Bax\/Bcl-2\/caspase-3 expression, and inhibited PI3K\/AKT\/mTOR as well as TGF-\u03b2 signaling, leading to significant attenuation of fibrosis. Conclusions: The current findings indicate that ivabradine exerts potent antioxidant, anti-inflammatory, anti-apoptotic, and antifibrotic actions against TAA-induced hepatic fibrosis. Future clinical studies are recommended to determine whether these protective effects translate to patients with chronic liver disease.<\/jats:p>","DOI":"10.3390\/ph19030504","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T11:50:36Z","timestamp":1773921036000},"page":"504","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ivabradine Attenuates Experimental Hepatic Fibrosis by Modulating Inflammatory and Apoptotic Signaling Pathways"],"prefix":"10.3390","volume":"19","author":[{"given":"Salman H.","family":"Alotaibi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud M.","family":"Samaha","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manar G.","family":"Helal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7545-6235","authenticated-orcid":false,"given":"Dina S.","family":"El-Agamy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1007\/s00210-022-02259-7","article-title":"Sesamol protects against liver fibrosis induced in rats by modulating lysophosphatidic acid receptor expression and TGF-\u03b2\/Smad3 signaling pathway","volume":"395","author":"Elrazik","year":"2022","journal-title":"Naunyn Schmiedebergs Arch. 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