The efficacy of tyrosine kinase inhibitor dasatinib on colonic mucosal damage in murine model of colitis

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• 作者：Gü ; ray Can^a ; ^{dr_guraycan@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; Sü ; leyman Ayvaz^b ; ^{suleyayvaz@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; Hatice Can^c ; ^{yailaslan@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; İhsan Karaboğa^d ; ^{ihsankaraboga@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Selim Demirtaş^d ; ^{selimdemirtas@trakya.edu.tr" class="auth_mail" title="E-mail the corresponding author} ; Hasan Akşit^e ; ^{vethas@hotmail.com" class="auth_mail" title="E-mail the corresponding author} ; Bü ; lent Yılmaz^f ; ^{dr.yilmazbulent@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Uğur Korkmaz^a ; ^{drkorkmazugur@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; Mevlü ; t Kurt^a ; ^{dr.mevlutkurt@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Turan Karaca^d ; ^{turankaraca@trakya.edu.tr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Ab ; Abelson ; CD ; Crohn's disease ; CML ; Chronic myeloid leukemia ; DAI ; Disease activity index ; DC ; Dentritic cell ; IBD ; Inflammatory bowel disease ; IL ; Interleukin ; LGL ; Large granular lymphocytosis ; MDA ; Malondialdehyde ; MPO ; Myeloperoxidase ; NFкβ ; Nuclear factor kappa beta ; PDGFR ; Platelet derived growth factor receptor ; SFK ; Src family kinases ; SOD ; Superoxide dismutase ; Syk ; Spleen tyrosine kinase ; TNFα ; Tumor necrosis factor-alpha ; TK ; Tyrosine kinase ; UC ; Ulcerative colitis
• 刊名：Clinics and Research in Hepatology and Gastroenterology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：40
• 期：4
• 页码：504-516
• 全文大小：3645 K

文摘

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, TNFα 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 TNFα. Dasatinib may be one of the treatment options for ulcerative colitis.