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    The efficacy of tyrosine kinase inhibitor dasatinib on colonic mucosal damage in murine model of colitis
    (Elsevier Masson, Corporation Office, 2016) Can, Guray; Ayvaz, Suleyrnan; Can, Hatice; Karaboga, Ihsan; Demirtas, Selim; Aksit, Hasan; Yilmaz, Bulent
    Background and objective: Ulcerative colitis is an inflammatory condition of the colon in the gastrointestinal system. Currently, the most potent medications used for ulcerative colitis produce no response in 20-30% of cases. There is a need for more efficient and reliable medications. Tyrosine kinase inhibitors have shown efficacy in some inflammatory diseases. Although dasatinib, a tyrosine kinase inhibitor, suppresses proinflammatory cytokines in colonic tissue, there are a few cases of hemorrhagic colitis with dasatinib. There is no study investigating the effect of dasatinib on experimental colitis. We aimed to investigate the effect of dasatinib in a colitis model induced with acetic acid in our study. Methods: In the study, 24 male Sprague-Dawley rats randomly distributed into 4 groups of 6 rats each as control, dasatinib, colitis and dasatinib + colitis groups. For colitis induction, 4% acetic acid was used. Sacrificing of the rats was performed on the seventh day. Disease activity, morphologic and histological injury, superoxide dismutase, myeloperoxidase and malondialdehyde activity, TNF alpha and CD3 expression were assessed in colonic tissue. Results: Apart from malondialdehyde, significant difference in all parameters between the control and colitis groups was determined. Difference between the colitis and colitis + dasatinib groups was not significant in only weight loss and biochemical parameters. Though dasatinib does not fully resolve the changes in colitis, there was significant regression. Conclusions: Dasatinib decreased the inflammation in a rodent model of colitis. It may be provide this effect by the suppression of TNF alpha. Dasatinib may be one of the treatment options for ulcerative colitis. (C) 2016 Elsevier Masson SAS. All rights reserved.
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    The Syk Inhibitor Fostamatinib Decreases the Severity of Colonic Mucosal Damage in a Rodent Model of Colitis
    (Oxford Univ Press, 2015) Can, Guray; Ayvaz, Suleyman; Can, Hatice; Demirtas, Selim; Aksit, Hasan; Yilmaz, Bulent; Korkmaz, Ugur
    Background and aims: Inflammatory bowel disease is a chronic inflammatory disease of the gastrointestinal system. In some cases, current medications used for inflammatory bowel disease may not be enough for remission, creating a need for more potent and reliable medications. There is no study showing the efficacy of fostamatinib, with proven effects on some inflammatory diseases, on ulcerative colitis. In our study we planned to research the efficacy of fostamatinib, a spleen tyrosine kinase inhibitor, on acetic acid-induced colitis. Methods: The study included 28 male Sprague-Dawley rats, randomly divided into control group, fostamatinib group, colitis group and fostamatinib + colitis group, each containing seven rats. Colitis induction was performed with 4% acetic acid. Colonic inflammation was assessed with disease activity index, macroscopic and histological damage scores, colonic myeloperoxidase, malondialdehyde and superoxide dismutase activity, and tumour necrosis factor alpha [TNF alpha], CD3, Syk, and phospho-Syk expression. Results: There was a significant difference between the colitis and control groups in terms of all parameters. The disease activity index, macroscopic and microscopic damage scores, immunohistochemical TNF alpha, CD3, Syk, and phospho-Syk expression, and tissue myeloperoxidase activity were found to be significantly lower in the colitis + fostamatinib group compared with the colitis group. There was no significant difference between the two groups in terms of myeloperoxidase and malondialdehyde activity. Conclusions: Fostamatinib reduced the inflammatory damage in the experimental colitis. This effect may be due to suppression of TNF alpha, T-lymphocytes, and neutrophils in colonic mucosa via suppression of Syk. Fostamatinib may be an appropriate treatment alternative for ulcerative colitis. Further clinical studies are required to support this.