Antiinflammatory effects of alosetron mediated through5HT3 receptors on experimental colitis

lt;p gt;Development of new medicine with fewer deleterious effects and more efficacies for treatment of inflammatory bowel disease is needed. 5Hydroxytryptamine 3 receptor (5HT lt;sub gt;3 lt;/sub gt;R) antagonists have exhibited analgesic and antiinflammatory features lt;em gt;in vitro lt;/em gt; and lt;em gt;in vivo lt;/em gt;. The present study was designed to evaluate the antiinflammatory effect of alosetron, a 5HT lt;sub gt;3 lt;/sub gt;R antagonist, on trinitrobenzenesulfonic acid (TNBS)induced ulcerative colitis in rats. Two h subsequent to induce colitis (intracolonic instillation of TNBS, 50 mg/kg) in male Wistar rats, alosetron (1 mg/kg), dexamethasone (1 mg/kg), metachlorophenylbiguanide (mCPBG, a 5HT lt;sub gt;3 lt;/sub gt;R agonist, 5 mg/kg), or alosetron + mCPBG were administrated intraperitoneally for 6 days. Animals were thereafter sacrificed and the efficacy of drugs was evaluated macroscopically, histologically, and biochemically (myeloperoxidase, tumor necrosis factoralpha, interleukin6, and interleukin1 beta) on distal colon samples. Treatment with alosetron and dexamethasone improved macroscopic and microscopic colonic damages significantly and decreased myeloperoxidase activity and colonic levels of inflammatory cytokines. The profitable effects of alosetron were antagonized by concurrent administration of mCPBG. Our data provided evidence that the protective effects of alosetron on TNBSinduced colitis can be mediated by 5HT3R. lt;/p gt;