Nilotinib-mediated mucosal healing in a rat model of colitis

AIM:To investigate the effects of nilotinib in a rat model of trinitrobenzene sulfonic acid(TNBS)-induced colitis.METHODS:Twenty-one Wistar albino female rats obtained from Dokuz Eylul University Department of Laboratory Animal Science were categorized into a control(n=7),TNBS(n=7)and nilotinib group(n=7).Saline was administered orally for 14 d to the control and the TNBS group.The TNBS group received rectal TNBS on the first day while saline was administered to the control group.The nilotinib group received 20mg/kg nilotinib for 14 d in 2 divided doses,starting the same day as TNBS administration.For 14 d,the rats were fed a standard diet,and their weights were recorded daily.After sacrifice,colon tissue samples from each group were scored for macroscopic and microscopic pathology.Apoptotic indices were determined by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method.Platelet-derived growth factor receptor(PDGFR)alpha and beta levels were assessed through immunohistochemistry staining scores and compared among the groups.Tissue and serum tumor necrosis factor(TNF)alpha levels were determined by enzyme-linked immunosorbent assay.RESULTS:Between days 1 and 14,the nilotinib group rats lost significantly less weight than the TNBS group rats(-0.7 g vs-14.0 g,P=0.047).The difference in weight between the control and nilotinib groups was also statistically significant(+8.3 gvs-0.7 g,P=0.031).From day 7 to day 14,the weight differences of the control group vs the TNBS group,the TNBS group vs the nilotinib group,and the control group vs the nilotinib group were all statistically significant(+8.0 g vs-11.1 g,P=0.007;-11.1 g vs+2.9 g,P=0.015;+8.0g vs+2.9 g,P=0.042,respectively).Macroscopic and microscopic scores were significantly lower in the nilotinib group than in the TNBS group(0.00±0.00 vs 1.43±0.65,P=0.009;2.86±0.55 vs 7.71±1.48,P=0.030,respectively).However,these scores were similar between the nilotinib and control groups.While no significant difference for the nilotinib vs