Experimental study on the potential effect and mechanisms of action of cilostazol alone or in combination with sulfasalazine in a model of ulcerative colitis /
دراسة تجريبية حول التأثير المحتمل و آلية عمل السيلوستازول بمفرده او مع السلفاسالازين في نموذج إلتهاب القولون التقرحي
Hiba Ali Abdulqader ; Supervised Hanan Salah Eldin Elabhar , May Ahmed Galal , Waleed Ali Mohamed
- Cairo : Hiba Ali Abdulqader , 2016
- 138 P. : charts , facsimiles ; 25cm
Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology
Inflammatory bowel diseases are immunologically-mediated disorders of gastrointestinal tract, characterized by dysregulated immune response that results in a chronic intestinal inflammation. The anti-platelet cilostazol, a phosphodiesterase-III inhibitor, exerted a beneficial effect in several models of gastrointestinal diseases. Therefore, the aim of the current study is to elucidate the potential role of cilostazol in a trinitrobenzenesulfonic acid (TNBS)-induced colitis model. Male Wistar rats were divided into sham, TNBS control, sulfasalazine (500 mg/kg), cilostazol (50 & 100 mg/kg) and a combination (sulfasalazine/cilostazol 50 mg/kg) treated groups. All treatments were gavaged for 14 days, with TNBS rectal administration on the 11th day. TNBS produced colitis manifested as body weight loss, a decrease in the epithelial junctional adhesion molecule-A (JAM-A) and an increase in trefoil factor-3, ulcerative area and colon mass index, parameters that collaborate with the gross macroscopic changes in colon tissue. Additionally, TNBS increased heme oxygenase (HO)-1, nuclear factor-mB, P-selectin and myeloperoxidase (MPO), as well as the apoptotic ratio of Bcl-2 associated X protein (Bax)/B Cell Lymphoma-2 (Bcl-2). Administration of cilostazol alone, especially at the high dose level, attenuated the severity of TNBS-induced colitis in a sulfasalazine comparable manner. Combination of the latter with cilostazol succeeded to normalize most of the measured parameters. In conclusion, cilostazol protected the colon against TNBS through its anti-inflammatory and anti-apoptotic effects along with its beneficial effect on tight junction. Furthermore, cilostazol can be beneficial as an add-on drug with the conventional treatments of colitis