World J Gastroenterol. 2013 Oct 7;19(37):6237-44.

Nilotinib-mediated mucosal healing in a rat model of colitis.

Ataca P, Soyturk M, Karaman M, Unlu M, Sagol O, Dervis Hakim G, Yilmaz O.

Pinar Ataca, Department of Internal Medicine, Dokuz Eylul University School of Medicine, Inciralti, Izmir 35340, Turkey.

 

Abstract

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 20 mg/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 g vs -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; +8.0 g 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 control groups could be determined for PDGFR alpha and beta scores, PDGFR alpha and beta scores were lower in the nilotinib group than in the TNBS group. Furthermore, the TNF alpha levels in the serum, tissue and apoptosis scores were similar between the nilotinib and TNBS groups.

CONCLUSION: Nilotinib prevents weight loss, facilitates mucosal healing by improving the pathological scores without introducing variation into the apoptotic scores or TNF alpha levels.

KEYWORDS: Inflammatory bowel disease, Mucosal healing, Platelet-derived growth factor receptor, Tumor necrosis factor alpha, Tyrosine kinase inhibitor

PMID: 24115822

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