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P038. Role of 5-HT3 receptors in the anti-inflammatory effects of alosetron in a rat model of colitis

A. Motavallian1, M. Minaiyan2, M. Rabbani2, P. Mahzouni2, 1Guilan University of Medical Sciences, Pharmacology, Guilan, Iran, Islamic Republic of, 2Isfahan university of medical sciences, pharmacology, Isfahan, Iran, Islamic Republic of

Background

The anti-inflammatory effect of alosetron, as a 5HT3 antagonist, through 5HT3 receptors on TNBS-induced colitis in rat was investigated.

Methods

The trinitrobenzenesulfonic acid (TNBS) model of colitis in the rat was used in the present study. Two hours subsequent to induction of colitis (instillation of TNBS with a dose of 50 mg/kg, via rectum) in male Wistar rats, alosetron (1 mg/kg), dexamethasone (1 mg/kg), meta-chlorophenylbiguanide (mCPBG, 5 mg/kg, a 5-HT3 receptor agonist) or alosetron + mCPBG were intraperitoneally (ip) administrated for 6 days. Animals were thereafter sacrificed; macroscopic, histological, biochemical (myeloperoxidase [MPO]) assessments and ELISA test (tumor necrosis factor-alpha [TNF-α], interleukin-6 [IL-6] and interleukin-1 beta [IL-1β]) were carried out on distal colon samples.

Results

Alosetron and dexamethasone treatment significantly decreased macroscopic and microscopic colonic damages. Furthermore a significant reduction in MPO activity and colonic levels of inflammatory cytokines was seen. The beneficial effects of alosetron were antagonized by concurrent administration of mCPBG.

Conclusion

The present study suggests that the protective effects of alosetron on TNBS-induced colitis can be mediated by 5-HT3 receptors.