{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T22:47:13Z","timestamp":1781477233729,"version":"3.54.1"},"reference-count":36,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,8,30]],"date-time":"2019-08-30T00:00:00Z","timestamp":1567123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>It has been shown that both nilotinib as a tyrosine kinase inhibitor, and atorvastatin as a rho\u2010kinase inhibitor, have antifibrotic effects. Therefore, considering the relationship between these two pathways, this study aimed to investigate the effects of their co\u2010treatment against hepatic stellate cells (<jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s) activation and liver fibrosis. For this purpose, the activation of <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s coincided with these therapies. Also, liver fibrosis by carbon tetrachloride (<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub>) was induced in male Wistar rats and treated simultaneously with these compounds. The expression of alpha\u2010smooth muscle actin (\u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>), connective tissue growth factor (<jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content>), Ras homolog gene family, and member A (RhoA)\/Rho\u2010associated protein kinase (<jats:styled-content style=\"fixed-case\">ROCK<\/jats:styled-content>) in <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s were measured. The expression of transforming growth factor beta\u20101 (<jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b21), its receptor (T\u03b2<jats:styled-content style=\"fixed-case\">RII<\/jats:styled-content>), <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content>, and platelets derived growth factor (<jats:styled-content style=\"fixed-case\">PDGF<\/jats:styled-content>), in the livers, were also investigated, all by real\u2010time <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> and western blot analysis. Also, histopathologic and immunohistochemical evaluations were performed to evaluate changes in liver fibrosis during treatment. The results indicated the down\u2010regulation of RhoA\/<jats:styled-content style=\"fixed-case\">ROCK<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> CTGF<\/jats:styled-content>, and \u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>, and inhibition of the <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s activation toward myofibroblasts. The results also showed that the combined use of atorvastatin and nilotinib has significantly higher inhibitory effects. The antifibrotic effects of atorvastatin and nilotinib co\u2010administration were also observed by histopathologic and immunohistochemical observations, and inhibiting the expression of <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b21, T\u03b2<jats:styled-content style=\"fixed-case\">RII<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> CTGF<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">PDGF<\/jats:styled-content>. Taken together, this study revealed that co\u2010administration of nilotinib\u2013atorvastatin has novel antifibrotic effects, by inhibiting RhoA\/<jats:styled-content style=\"fixed-case\">ROCK<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content> pathway. Therefore, the importance of the common pathway of RhoA\/<jats:styled-content style=\"fixed-case\">ROCK<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content>, in reducing fibrosis may almost be concluded.<\/jats:p>","DOI":"10.1111\/1440-1681.13157","type":"journal-article","created":{"date-parts":[[2019,8,9]],"date-time":"2019-08-09T07:55:55Z","timestamp":1565337355000},"page":"1183-1193","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Increasing the effectiveness of tyrosine kinase inhibitor (<scp>TKI<\/scp>) in combination with a statin in reducing liver fibrosis"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2598-9439","authenticated-orcid":false,"given":"Adel","family":"Mohammadalipour","sequence":"first","affiliation":[{"name":"Baqiyatallah Research Center for Gastroenterology and Liver Diseases Baqiyatallah University of 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