{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:40:02Z","timestamp":1792024802225,"version":"4.4.0"},"reference-count":87,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,4,27]],"date-time":"2016-04-27T00:00:00Z","timestamp":1461715200000},"content-version":"vor","delay-in-days":117,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["NFG-14-02-13"],"award-info":[{"award-number":["NFG-14-02-13"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:p><jats:italic>Background and Objective.<\/jats:italic> High\u2010cholesterol diet (HCD) intends to increase the oxidative stress in liver tissues inducing hepatotoxicity. Rutin is a natural flavonoid (vitamin p) which is known to have antioxidative properties. The aim of the present study was to investigate the potential effects of Rutin on hypercholesterolemia\u2010induced hepatotoxicity in rats. <jats:italic>Materials and Methods.<\/jats:italic> Male Wistar rats were divided into four groups: G\u2010I control, G\u2010II Rutin, G\u2010III HCD, and G\u2010IV Rutin + HCD. The liver functions and lipid profile were used to evaluate the HCD\u2010induced hepatotoxicity. Quantitative real time\u2010PCR was carried out to evaluate the expression levels of genes in TGF\u2010<jats:italic>\u03b2<\/jats:italic>\/Smad signaling pathway. <jats:italic>Results.<\/jats:italic> Rutin in combination with HCD showed a significant protective effect against hepatotoxicity. HCD caused significant increase in the mRNA expression of transforming growth factor beta (<jats:italic>TGF-\u03b2<\/jats:italic>), Mothers Against Decapentaplegic Homolog 2 (<jats:italic>Smad-2<\/jats:italic>), Mothers Against Decapentaplegic Homolog 4 (<jats:italic>Smad-4<\/jats:italic>), Bcl\u20102\u2010binding component 3 (<jats:italic>Bbc3<\/jats:italic>), <jats:italic>caspase-3<\/jats:italic>, <jats:italic>P53<\/jats:italic> and Interleukin\u20106 (<jats:italic>IL-6<\/jats:italic>) and decrease in the expression levels of Cyclin depended kinase inhibitor (<jats:italic>P21<\/jats:italic>) and Interleukin\u20103 <jats:italic>(IL-3<\/jats:italic>) in hepatic cells. <jats:italic>Conclusion. TGF-\u03b2\/Smad<\/jats:italic> signaling pathway is involved in HCD\u2010induced hepatotoxicity and Rutin inhibits the hepatotoxicity via suppressing this pathway. Therefore, Rutin might be considered as a protective agent for hepatotoxicity.<\/jats:p>","DOI":"10.1155\/2016\/5436745","type":"journal-article","created":{"date-parts":[[2016,4,27]],"date-time":"2016-04-27T23:10:15Z","timestamp":1461798615000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Rutin Attenuates Hepatotoxicity in High\u2010Cholesterol\u2010Diet\u2010Fed Rats"],"prefix":"10.1155","volume":"2016","author":[{"given":"Shakir D.","family":"AlSharari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim S.","family":"Al-Rejaie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatem M.","family":"Abuohashish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed 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