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The study was designed to evaluate hepatoprotective effect of <jats:styled-content style=\"fixed-case\">BCAA<\/jats:styled-content>s on <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub>\u2010induced liver fibrosis and to investigate the molecular mechanisms underlying these effects in rats. In all, 30 male rats were divided into three groups. Control group (<jats:italic>n<\/jats:italic> = 10) and <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> group (<jats:italic>n<\/jats:italic> = 10), where rats were injected with <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> (1 <jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content>\/kg of 0.5 : 1 v\/v injected i.p. twice weekly for 12 weeks). In <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> + <jats:styled-content style=\"fixed-case\">BCAA<\/jats:styled-content>s group (<jats:italic>n<\/jats:italic> = 10), rats were injected with similar doses of <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> and supplemented with a mixture of 600 mg\/kg <jats:styled-content style=\"fixed-case\">BCAA<\/jats:styled-content>s (2 : 1 : 1.2 leucine : isoleucine : valine) by oral gavage, three times\/week for 12 weeks. Liver fibrosis was assessed by measuring total bilirubin, total protein, alanine aminotransferase, and aspartate aminotransferase, hydroxyproline content, and serum <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010. Histopathologic studies and \u03b1\u2010smooth muscle actin (\u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>) were detected immunohistochemically in liver. Serum insulin level, blood glucose, liver malodialdehyde concentration (<jats:styled-content style=\"fixed-case\">MDA<\/jats:styled-content>), glutathione peroxidase, and superoxide dismutase (<jats:styled-content style=\"fixed-case\">SOD<\/jats:styled-content>) activities were quantified. <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b21, Smad3, and Smad7 gene expressions were estimated by <jats:styled-content style=\"fixed-case\">qRT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">BCAA<\/jats:styled-content>s suppressed liver fibrosis induced by <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> treatment. <jats:styled-content style=\"fixed-case\">BCAA<\/jats:styled-content>s modulated liver indices and downregulated <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b21, Smad3, and Smad7 expressions in hepatocytes. <jats:styled-content style=\"fixed-case\">BCAA<\/jats:styled-content>s enhanced liver antioxidant enzyme activities (<jats:italic>P<\/jats:italic> &lt; 0.001), reduced serum levels of <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b21, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106, and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010 compared to <jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content><jats:sub>4<\/jats:sub> group and ameliorated histopathologic changes in rat liver. <jats:styled-content style=\"fixed-case\">BCAA<\/jats:styled-content>s may have a protective role against liver fibrosis via antioxidant and anti\u2010inflammatory mechanisms.<\/jats:p>","DOI":"10.1111\/fcp.12297","type":"journal-article","created":{"date-parts":[[2017,5,24]],"date-time":"2017-05-24T01:06:34Z","timestamp":1495587994000},"page":"534-545","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Branched chain amino acids supplementation modulates <scp>TGF<\/scp>\u2010\u03b21\/Smad signaling pathway and interleukins in <scp>CC<\/scp>l<sub>4<\/sub>\u2010induced liver fibrosis"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6508-8440","authenticated-orcid":false,"given":"Naglaa F.","family":"Khedr","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy Tanta University Postal number: 31527 Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman G.","family":"Khedr","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Tanta University Postal number: 31527 Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755-1536-6-19"},{"key":"e_1_2_8_3_1","first-page":"191","article-title":"Antioxidant and anti\u2010inflammatory effects of curcumin on CCl4 \u2013 induced liver fibrosis in rats","volume":"6","author":"Khedr N.F.","year":"2014","journal-title":"AJB Sci."},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v18.i45.6605"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/764641"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27332"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1246-y"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26007"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986712803341520"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i43.7620"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/364976"},{"key":"e_1_2_8_12_1","first-page":"49","article-title":"Efficacy of curcumin in protecting the rat liver from CCl4\u2010induced injury and fibrogenesis, histological and immunohistochemical study","volume":"10","author":"Mohamed S.H.","year":"2013","journal-title":"Life Sci. 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