Tracking anti‐fibrotic pathways of nilotinib and imatinib in experimentally induced liver fibrosis: A n insight

• Published in: Clinical and experimental pharmacology & physiology 2014-10, Vol.41 (10), p.788-797
• Main Authors: Shiha, Gamal E, Abu‐Elsaad, Nashwa M, Zalata, Khaled R, Ibrahim, Tarek M
• Format: Article
• Language: English
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/1440-1681.12286

The tyrosine kinase inhibitors imatinib and nilotinib have been suggested to have promising antifibrotic activity in experimental models of liver fibrosis. 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 CC l 4 for 12 weeks. During the last 8 weeks of treatment, rats were also injected daily intraperitoneally with 20 mg/kg imatinib or 20, 10 or 5 mg/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‐inflammatory effects were estimated by measuring levels of inflammatory cytokines in liver tissue. Liver expression of α ‐smooth muscle actin, transforming growth factor ( TGF )‐ β 1 antibodies and platelet‐derived growth factor receptor β ( PDGFR β ) was evaluated by immunohistochemical staining techniques. Nilotinib (5 and 10 mg/kg) significantly ( P