Abstract
BACKGROUND: Inflammatory bowel diseases are immunologically mediated disorders of gastrointestinal tract, characterized by dysregulated immune responses that result in a chronic intestinal inflammation. The antiplatelet cilostazol (CS), a phosphodiesterase-III inhibitor, exerted a beneficial effect on several models of gastrointestinal diseases; however, the full mechanism of action in this context has not been unveiled. AIM: The current study aimed to elucidate the potential role of CS in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model. METHODS: Male Wistar rats were divided into a sham group and groups treated with sulfasalazine (500 mg/kg), CS (50 and 100 mg/kg), and a combination (sulfasalazine/CS 50 mg/kg). All treatments were administered orally 15 days, with TNBS rectal administration on the 11th day. RESULTS: TNBS-produced colitis manifested as a decrease in the epithelial junctional adhesion molecule-A (JAM-A) and as an increase in trefoil factor-3, ulcerative area, and colon mass index, parameters that collaborate with the gross macroscopic changes in colon tissue. In addition, TNBS increased hemeoxygenase-1, nuclear factor-kappa B, P-selectin, and myeloperoxidase, as well as the apoptotic ratio of Bax/Bcl-2. Administration of CS alone, especially at the high dose level, attenuated the severity of TNBS-induced colitis in a sulfasalazine-comparable manner. In addition, a better effect was mediated by the combination regimen, which succeeded in normalizing most of the measured parameters. CONCLUSION: CS protected the colon against TNBS through its anti-inflammatory and antiapoptotic effects along with maintaining cellular tight junctions (TJs). Furthermore, CS can be beneficial as an add-on drug with the conventional treatments of colitis.