Imatinib, the best-known member of this class of drugs, is specific for TK receptor sites and suppresses the Abelson proto-oncogene (ABL), the c-kit proto-oncogene, platelet-derived growth factor receptor (PDGFR), macrophage colony-stimulating factor receptor, http://www.selleckchem.com/products/Oligomycin-A.html TNF alpha, and inducible nitric oxide synthase[13]. Nilotinib is a more potent inhibitor of TKs than imatinib. In studies involving patients with lung fibrosis, nilotinib has been shown to reduce interleukin (IL)-6, IL-1 beta, TNF alpha, tumor growth factor beta 1, and PDGFR beta levels more significantly than imatinib and had a potent antifibrotic effect[14]. In the literature, there are a few reports suggesting that TK inhibitors may be effective in IBD.

In a case report by Magro et al[15], a patient diagnosed with Crohn��s disease (CD) and chronic myeloid leukemia (CML) remained in remission for 3 years on imatinib therapy alone, without the use of mesalamine or steroids. Cuzzocrea et al[16] demonstrated that the development of colitis in dinitrobenzene sulfonic acid (DNBS)-induced colitis animal models was reduced by the TK inhibitor tyrphostin AG126. The present study was planned based on the demonstrated success of nilotinib in previous studies and on the fact that TK inhibitors affect several key components in the pathogenesis of IBD, including TNF alpha, PDGFR, and nitric oxide (NO) synthesis. For this purpose, we evaluated the efficacy of nilotinib on weight, macroscopic and microscopic pathological scores, TNF alpha levels, PDGFR levels, and the apoptotic index in a rat model of trinitrobenzene sulfonic acid (TNBS)-induced colitis.

This study is the first to evaluate the efficacy of nilotinib in a rat colitis model. MATERIALS AND METHODS Experimental design Approval was obtained from the animal ethics council of Dokuz Eylul University Medical Faculty (DEUTF). The DEUTF Hospital Experimental Research Laboratory provided 21 female Wistar albino rats weighing 200-250 g (mean weight: 209.43 �� 8.92 g) for use in this study. The rats were maintained in a room at a temperature of 23 �� 2 ��C under a 12-h light/dark cycle at the DEUTF Experimental Animal Laboratory. Before and during the study, they were fed a standard diet, and their weights were monitored daily. The animals were also allowed water ad libitum. The rats were divided into 3 groups, each consisting of 7 rats: the control group, TNBS group and nilotinib group.

After 24 h of fasting, 0.25 mL of the physiological serum was intracolonically administered to the control group rats through a cannula inserted 8 cm proximal to the anus, using a rectally inserted flexible polypropylene catheter. To induce colitis, the Carfilzomib rats in the other 2 groups received an intracolonic solution treated with 0.5 mL of 100 mg/mL TNBS (Sigma, Germany) dissolved in 30% ethanol and administered through a cannula.