Abstract
There is a pressing need for research that will lead to the reveal of targets designed to analyse the possible pathways for the treatment of IBD. Because of the probable involvement of serotonin in inflammatory conditions of intestine and the important role of 5HT4 receptors in GI function, the investigation of the role of 5HT4 receptors in the pathogenesis of IBD will be interesting. The aim of this study was to investigate the effects of cisapride, a 5HT4 receptor agonist, in trinitrobenzenesulfonic-acid-(TNBS) induced rat colitis. Two hours subsequent to induction of colitis using TNBS in rats, cisapride (2 mg/kg, intraperitoneally (i.p); 4 mg/kg, orally (p.o)) and dexamethasone (1 mg/kg, i.p; 2 mg/kg, p.o) were administrated for 6 days. Animals were thereafter euthanized; macroscopic, histological, and biochemical assessments and ELISA test were carried out on distal colon samples. Our data showed that dexamethasone treatment (i.p, p.o) significantly decreased macroscopic and microscopic damage and also biochemical markers, but there were no significant differences in aforementioned parameters between cisapride (i.p or p.o) and TNBS-treated rats. It can be deduced that because the severity of colitis produced by TNBS is massive (through various pathways), cisapride could not bring about more colitis damages through 5HT4 receptors. Based on the present study further researches are required for investigating the exact roles of 5HT4 receptors in the pathogenesis of ulcerative colitis.
Highlights
Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic inflammatory disorder of the gastrointestinal (GI) tract characterized by a relapsing course [1]
The present study assessed the effects of administration of cisapride on the severity of experimental colitis in rats
An increase was found in the bioavailability of 5-HT from mucosal epithelial cells in TNBS-induced colitis [16]
Summary
Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic inflammatory disorder of the gastrointestinal (GI) tract characterized by a relapsing course [1]. Despite extensive research in the last decades, the etiology of IBD and the initial event of the inflammatory cascade still remain ambiguous [2]. IBD is characterized by massive cellular infiltrates and pertains to abnormalities of the immune system involving heightened number of CD4+ T lymphocytes, mast cells, neutrophils, and eosinophils [4]. These conditions bring about inflammation, ulceration, edema, diarrhea accompanied by blood and/or mucus, fever, abdominal pain and gastric dysmotility, anemia, weight loss, and a range of extraintestinal symptoms [5]. Many medical therapies have been proposed for IBD like salicylates, glucocorticoids, and immunosuppressives; available medicines are not universally effective and result in marked deleterious effects, and the medical management of IBD remains challenging, and investigations on novel treatments are required [6]
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