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The aim of the present study was to investigate new pathways underlying this beneficial effect. Hepatic injury was induced in male Wistar rats by intraperitoneal injection of\n                    <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>\n                    l\n                    <jats:sub>4<\/jats:sub>\n                    for 12\u00a0weeks. During the last 8\u00a0weeks of treatment, rats were also injected daily intraperitoneally with 20\u00a0mg\/kg imatinib or 20, 10 or 5\u00a0mg\/kg nilotinib. At the end of treatment, effects on fibrosis were assessed by measuring serum fibrotic markers and profibrogenic cytokines, as well as by histopathological examination. Possible anti\u2010inflammatory effects were estimated by measuring levels of inflammatory cytokines in liver tissue. Liver expression of\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010smooth muscle actin, transforming growth factor (\n                    <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\n                    )\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    1 antibodies and platelet\u2010derived growth factor receptor\n                    <jats:italic>\u03b2<\/jats:italic>\n                    (\n                    <jats:styled-content style=\"fixed-case\">PDGFR<\/jats:styled-content>\n                    <jats:italic>\u03b2<\/jats:italic>\n                    ) was evaluated by immunohistochemical staining techniques. Nilotinib (5 and 10\u00a0mg\/kg) significantly (\n                    <jats:italic>P\u00a0<\/jats:italic>\n                    &lt;\u00a00.05) decreased all serum fibrotic markers measured, but 20\u00a0mg\/kg of either nilotinib or imatinib had limited effects. At all doses tested, nilotinib significantly (\n                    <jats:italic>P\u00a0<\/jats:italic>\n                    &lt;\u00a00.05) decreased the\n                    <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>\n                    l\n                    <jats:sub>4<\/jats:sub>\n                    \u2010induced increases in tissue inflammatory cytokines. Furthermore, 5 and 10\u00a0mg\/kg nilotinib significantly decreased\n                    <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\n                    \u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    1 levels and tissue expression of its antibody, as well expression of\n                    <jats:styled-content style=\"fixed-case\">PDGFR<\/jats:styled-content>\n                    <jats:italic>\u03b2<\/jats:italic>\n                    . In conclusion, low doses (5 and 10 but not 20\u00a0mg\/kg) of nilotinib, rather than imatinib, can control hepatic fibrosis by regulating levels of proinflammatory cytokines, primarily interleukin (\n                    <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                    )\u20101 and\n                    <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                    \u20106. Nilotinib also controls the signalling pathways of profibrogenic cytokines by lowering\n                    <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\n                    \u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    1 levels and decreasing expression of\n                    <jats:styled-content style=\"fixed-case\">PDGFR<\/jats:styled-content>\n                    <jats:italic>\u03b2<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/1440-1681.12286","type":"journal-article","created":{"date-parts":[[2014,8,12]],"date-time":"2014-08-12T08:37:55Z","timestamp":1407832675000},"page":"788-797","source":"Crossref","is-referenced-by-count":37,"title":["Tracking anti\u2010fibrotic pathways of nilotinib and imatinib in experimentally induced liver fibrosis:\n                    <scp>A<\/scp>\n                    n insight"],"prefix":"10.1111","volume":"41","author":[{"given":"Gamal E","family":"Shiha","sequence":"first","affiliation":[{"name":"Departments of Internal Medicine Mansoura University Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nashwa M","family":"Abu\u2010Elsaad","sequence":"additional","affiliation":[{"name":"Department of Pathology Faculty of Medicine Mansoura University Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled R","family":"Zalata","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Faculty of Pharmacy Mansoura University Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek M","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Pathology Faculty of Medicine Mansoura University Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,10,30]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.084145"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-8539-7"},{"key":"e_1_2_6_4_1","first-page":"w13050","article-title":"Are tyrosine kinase inhibitors promising for the treatment of systemic sclerosis and other fibrotic diseases?","volume":"140","author":"Beyer C","year":"2010","journal-title":"Swiss Med. 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