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Hepatic fibrosis is a pathological state characterized by over accumulation of extracellular matrix (ECM) including collagen fibers. Sildenafil (a selective inhibitor of type 5 phosphodiesterase) has anti-inflammatory, antioxidant and anti-apoptotic properties. It is commonly used to treat erectile dysfunction in male. The purpose of the current investigation was to evaluate sildenafil\u2019s hepatoprotective potential against liver fibrosis in rats that was caused by carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>). Liver enzymes and oxidative markers as well as profibrotic genes were determined. The findings showed that sildenafil alleviates the hepatic dysfunctions caused by CCl<jats:sub>4<\/jats:sub> by restoring normal levels of ALT, AST, and GGT as well as by restoring the antioxidant status demonstrated by increased glutathione (GSH), and catalase. In addition, a significantly down-regulated the mRNA expressions of profibrotic genes [collagen-1\u03b1, IL-1\u03b2, osteopontin (OPN), and transforming growth factor-\u03b2 (TGF-\u03b2)]. Additionally, sildenafil lessens the periportal fibrosis between hepatic lobules, congestion and dilatation in the central vein, and the inflammatory cell infiltrations. As a result, it is hypothesized that sildenafil may be helpful in the management of hepatotoxicity brought on by CCl<jats:sub>4<\/jats:sub> through suppressing OPN.<\/jats:p>","DOI":"10.1038\/s41598-024-67305-1","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T11:14:18Z","timestamp":1721733258000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Ameliorative effects of sildenafil against carbon tetrachloride induced hepatic fibrosis in rat model through downregulation of osteopontin gene expression"],"prefix":"10.1038","volume":"14","author":[{"given":"Hend Elsayed","family":"Nasr","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8606-5937","authenticated-orcid":false,"given":"Ahmed Medhat","family":"Hegazy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha Osama","family":"El-Shaer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabab Shaban","family":"El-shafey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salwa A.","family":"Elgendy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba A.","family":"Elnoury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walaa Bayoumie El","family":"Gazzar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina Abdelhady","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,23]]},"reference":[{"issue":"1","key":"67305_CR1","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/s41420-022-01173-4","volume":"8","author":"T Zhao","year":"2022","unstructured":"Zhao, T. et al. 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