P077 The efficacy of tyrosine kinase inhibitor dasatinib on colonic mucosal damage in murine model of colitis
G. Can*1, S. Ayvaz2, H. Can3, I. Karaboğa4, S. Demirtaş4, H. Akşit5, B. Yilmaz6, U. Korkmaz7, M. Kurt7, T. Karaca4
1Abant Izzet Baysal University, Faculty of Medicine, Department of Gastroenterology, Bolu, Turkey, 2Trakya University, Faculty of Medicine, Department of Paediatric Surgery, Edirne, Turkey, 3Abant Izzet Baysal University, Faculty of Medicine, Department of Internal Medicine, Bolu, Turkey, 4Trakya University, Faculty of Medicine, Department of Histology and Embryology, Edirne, Turkey, 5Balikesir University, Faculty of Veterinary, Balikesir, Turkey, 6Selcuk University, Faculty of Medicine, Department of Gastroenterology, Konya, Turkey, 7Abant Izzet Baysal University, Medical Faculty, Department of Gastroenterology, Bolu, Turkey
Ulcerative colitis is an inflammatory condition limited to the colon in the gastrointestinal system. Currently the most potent medications used for medical treatment of ulcerative colitis produce no response in 20%–30% of cases, in spite of a high side-effect profile. There is a need for more efficient and reliable medications. Tyrosine kinase inhibitors have shown efficacy in some inflammatory diseases and in experimental colitis models. Even though dasatinib, a tyrosine kinase inhibitor, suppresses proinflammatory cytokines in colonic tissue, there are a few case reports of haemorrhagic colitis with use of the medication. 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.
In the study, 24 male Sprague-Dawley rats distributed into 4 groups of 6 rats each as control, dasatinib, colitis, and dasatinib+colitis groups randomly. 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; and TNFα and CD3 expression were assessed in colonic tissue.
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 only in weight loss and biochemical parameters. Though dasatinib does not fully resolve clinical and inflammatory changes related to colitis, there was significant regression.
Figure 1. Macroscopic damage scoring.
Figure 2. Microscopic damage scoring.
A tyrosine kinase inhibitor, dasatinib, decreased the inflammation in a rodent model of colitis. It may provide this effect by the suppression of TNFα. Dasatinib may be one of the treatment options for ulcerative colitis; however, this finding must be supported with advanced clinical studies.