{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T17:21:15Z","timestamp":1786296075824,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,2,26]],"date-time":"2013-02-26T00:00:00Z","timestamp":1361836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Fluorofenidone (<jats:styled-content style=\"fixed-case\">AKF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>) is a novel pyridone agent. The purpose of this study is to investigate the inhibitory effects of <jats:styled-content style=\"fixed-case\">AKF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> on dimethylnitrosamine (<jats:styled-content style=\"fixed-case\">DMN<\/jats:styled-content>)\u2010induced liver fibrosis in rats and the involved molecular mechanism related to hepatic stellate cells (<jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s).<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Wistar rats were randomly divided into normal control, <jats:styled-content style=\"fixed-case\">DMN<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> DMN<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">AKF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> treatment and <jats:styled-content style=\"fixed-case\">DMN<\/jats:styled-content>\/pirfenidone (<jats:styled-content style=\"fixed-case\">PFD<\/jats:styled-content>) treatment groups. <jats:styled-content style=\"fixed-case\">AKF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PFD<\/jats:styled-content> treatments were, respectively, performed for two activated <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s lines, rat <jats:styled-content style=\"fixed-case\">CFSC<\/jats:styled-content>\u20102G and human <jats:styled-content style=\"fixed-case\">LX<\/jats:styled-content>2. The cell proliferation was analysed by <jats:styled-content style=\"fixed-case\">MTT<\/jats:styled-content>. The expression of collagen I was determined by immunohistochemical staining and real\u2010time <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>. The expression of \u03b1\u2010smooth muscle actin (\u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>), tissue inhibitor of metalloproteinases\u20101 (<jats:styled-content style=\"fixed-case\">TIMP<\/jats:styled-content>\u20101), extracellular signal regulated kinase (<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2), p38 <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> (p38), and c\u2010Jun N\u2010terminal kinase\/stress\u2010activated protein kinase (<jats:styled-content style=\"fixed-case\">JNK<\/jats:styled-content>) were also detected by real\u2010time <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> and\/or Western blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AKF\u2010PD significantly reduced PDGF\u2010BB\u2010induced proliferation and activation of HSCs, as determined by reducing protein expression of \u03b1\u2010SMA and TIMP\u20101. AKF\u2010PD treatment attenuated PDGF\u2010BB\u2010induced upregulation of phosphorylation of ERK1\/2, p38 and JNK. In fibrotic rat liver, AKF\u2010PD reduced the degree of liver injury and hepatic fibrosis, which was associated with reduced the expression of collagen I, \u03b1\u2010SMA, TIMP\u20101 at both <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">AKF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> treatment inhibits the progression of hepatic fibrosis by suppressing <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s proliferation and activation via <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> signalling 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