title: Anti-inflammatory effect of ondansetron through 5-HT3 receptors on TNBS-induced colitis in rat.
abstract: Inﬂammatory bowel disease (IBD) is a chronic inﬂammatory disorder of the intestinal tract whose etiology has not yet been fully elucidated. Available medicines for treatment of IBD are not universally effective and result in marked deleterious effects. This challenge has thus heightened the need for research in order to adopt new therapeutic approaches for the treatment of IBD. 5-HT3 receptor antagonists have shown analgesic and anti-inflammatory properties in vitro and in vivo. Our aim was to investigate the effect of ondansetron, 5-HT3 receptor antagonist, in an immune-based animal model of IBD, trinitrobenzene sulfonic acid (TNBS)-induced rat colitis and probable involvement of 5-HT3 receptors. Two hours after induction of colitis (instillation of 50 mg/kg of TNBS dissolved in 0.25 ml of ethanol 50 % v/v) to male Wistar rats, ondansetron (2 mg/kg), dexamethasone (1 mg/kg), meta-chlorophenylbiguanide (mCPBG, 5 mg/kg), a 5-HT3 receptor agonist, or ondansetron + mCPBG were administrated intraperitoneally (ip) and continued daily for six days. The animals were sacrificed and distal colons were assessed macroscopically, histologically and biochemically [myeloperoxidase (MPO), tumor necrosis factor-alpha, interleukin-6 and interleukin-1 beta]. Ondansetron and dexamethasone resulted in a decrease in macroscopic and microscopic colonic damage significantly. In addition a dramatic reduction in MPO activity and colonic levels of inflammatory cytokines were seen. The protective effects of ondansetron were antagonized by concurrent administration of mCPBG. Our data suggests that the beneficial effects of ondansetron in TNBS-induced colitis could be mediated by 5-HT3 receptors.
authors.affiliation: Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, School of Pharmacy and Pharmaceutical Sciences, Isfahan, Iran, Tel. +983117922628;
authors.forename: Azadeh
authors.initials: A
authors.lastname: Motavallian-Naeini
authors.affiliation: Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, School of Pharmacy and Pharmaceutical Sciences, Isfahan, Iran; Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Minaiyan
authors.affiliation: Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, School of Pharmacy and Pharmaceutical Sciences, Isfahan, Iran; Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Rabbani
authors.affiliation: Department of Clinical Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Parvin
authors.initials: P
authors.lastname: Mahzuni
keywords: 5-HT3 receptor; TNBS-induced colitis; inflammatory bowel diseases; ondansetron