Involvement of 5HT3 Receptors in Anti-Inflammatory Effects of Tropisetron on Experimental TNBS-Induced Colitis in Rat.
BACKGROUND
There is a pressing need for research leading to the development of new effective drugs with lower side effects and more efficacy for treating inflammatory bowel disease (IBD). The analgesic and anti-inflammatory properties of 5-Hydroxytryptamine (5-HT)-3 receptor antagonists have been shown in in vivo and in vitro studies. The present study was designed to investigate the effects of tropisetron, a 5-HT3 receptor antagonist, on an immune-based animal model of IBD.


METHODS
In the present study, the trinitrobenzenesulfonic acid (TNBS) model of colitis in the rat was used. Two hours after induction of colitis in rats, tropisetron (2 mg/kg), dexamethasone (1 mg/kg), meta-chlorophenylbiguanide (mCPBG, 5 mg/kg), a 5-HT3 receptor agonist, or tropisetron + mCPBG were intraperitoneally (i.p.) administrated for 6 days. Animals were then sacrificed; macroscopic, histological, biochemical (myeloperoxidase [MPO]) assessments and ELISA test (tumor necrosis factor-alpha, interleukin-6 and interleukin-1 beta) were performed on distal colon samples.


RESULTS
Tropisetron or dexamethasone treatment significantly reduced macroscopic and microscopic colonic damages. In addition, a significant reduction in MPO activity and colonic levels of inflammatory cytokines was seen. The beneficial effects of tropisetron were antagonized by concurrent administration of mCPBG.


CONCLUSIONS
The present study indicates that the protective effects of tropisetron on TNBS-induced colitis can be mediated by 5-HT3 receptors.
Department of Pharmacology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
Azadeh
A
Motavallian
Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Mohsen
M
Minaiyan
Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Mohammad
M
Rabbani
Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Sasan
S
Andalib
Department of Clinical Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Parvin
P
Mahzouni
5-HT3 receptor; TNBS-induced colitis; Tropisetron; Ulcerative colitis