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

Abstract

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.