Anti-inflammatory effects of alosetron mediated through5-HT3 receptors on experimental colitis

Azadeh Motavallian , Mohsen Minaiyan , Mohammad Rabbani, Parvin Mahzouni, Sasan Andalib

Abstract


Development of new medicine with fewer deleterious effects and more efficacies for treatment of inflammatory bowel disease is needed. 5-Hydroxytryptamine 3 receptor (5-HT3R) antagonists have exhibited analgesic and anti-inflammatory features in vitro and in vivo. The present study was designed to evaluate the anti-inflammatory effect of alosetron, a 5-HT3R 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), meta-chlorophenylbiguanide (mCPBG, a 5-HT3R 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 factor-alpha, interleukin-6, and interleukin-1 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 TNBS-induced colitis can be mediated by 5-HT3R.


Keywords


Alosetron; Inflammatory bowel disease; Colitis; 5-HT3 receptor; TNBS.

Full Text:

PDF

References


Baumaqart DC, Sandborn WJ. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet. 2007;369(9573): 1641-1657.

Kucharzik T, Maaser C, Lügering A, Kagnoff M, Mayer L, Targan S, et al. Recent understanding of IBD pathogenesis: implications for future therapies. Inflamm Bowel Dis. 2006;12(11):1068-1083.

Grisham MB. Molecular and cellular aspects of intestinal inflammation: clinical implications in inflammatory bowel disease. Inflamm Bowel Dis. 2000;1:1-14.

Braus NA, Elliott DE. Advances in the pathogenesis and treatment of IBD. Clin Immunol. 2009;132(1): 1-9.

Hasler WL. Serotonin and the GI tract. Curr Gastroenterol Rep. 2009;11(5):383-391.

Idzko M, Panther E, Stratz C, Muller T, Bayer H, Zissel G, et al. The serotoninergic receptors of human dendritic cells: identification and coupling to cytokine release. J Immunol. 2004;172(10):6011-6019.

Coates MD, Mahoney CR, Linden DR, Sampson JE, Chen J, Blaszyk H, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004;126(7):1657-1664.

Fiebich BL, Akundi RS, Seidel M, Geyer V, Haus U, Müller W, et al. Expression of 5-HT3A receptors in cells of the immune system. Scand J Rheumatol Suppl. 2004;119:9-11.

Kris MG. Ondansetron: a specific serotonin antagonist for the prevention of chemotherapy induced vomiting. Important Adv Oncol. 1994:165-177.

McCleane GJ, Suzuki R, Dickenson AH. Does a single intravenous injection of the 5ht3 receptor antagonist ondansetron have an analgesic effect in neuropathic pain? A double-blinded, placebo-controlled cross-over study. Anesth Analg. 2003;97(5):1474-1478.

Muller W, Fiebich BL, Stratz T. New treatment options using 5-HT3 receptor antagonists in rheumatic diseases. Curr Top Med Chem. 2006;6(18):2035-2042.

Fiebich BL, Akundi RS, Lieb K, Candelario-Jalil E, Gmeiner D, Haus U, et al. Antiinflammatory effects of 5-HT3 receptor antagonists in lipopolysaccharide-stimulated primary human monocytes. Scand J Rheumatol Suppl. 2004;119:28-32.

Andresen V, Montori VM, Keller J, West CP, Layer P, Camilleri M. Effects of 5-hydroxytryptamine (serotonin) type 3 antagonists on symptom relief and constipation in nonconstipated irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. Clin Gastroenterol Hepatol. 2008;6(5):545-555.

Chang L, Chey WD, Harris L, Olden K, Surawicz C, Schoenfeld P. Incidence of ischemic colitis and serious complications of constipation among patients using alosetron: systematic review of clinical trials and post-marketing surveillance data. Am J Gastroenterol. 2006;101(5):1069-1079.

Li Z, Zhang X, Xu H, Sung JJY, Bian ZX. Intracolonical administration of protease activated receptor-2 agonists produced visceral hyperalgesia by up-regulating serotonin in the colon of rats. Eur J Pharmacol. 2009;606(1-3):199-204.

Motavallian-Naeini A, Andalib S, Rabbani M, Mahzouni P, Afsharipour M, Minaiyan M. Validation and optimization of experimental colitis induction in rats using 2, 4, 6-tri- nitrobenzene sulfonic acid. Res Pharm Sci. 2012;7(3):159-169.

Linden DR, Chen JX, Gershon MD, Sharkey KA, Mawe GM. Serotonin availability is increased in mucosa of guinea pigs with TNBS-induced colitis. Am J Physiol Gastrointest Liver Physiol. 2003;285(1):G207-G216.

Ajuebor MN, Hogaboam CM, Kunkel SL, Proudfoot AE, Wallace JL. The chemokine RANTES is a crucial mediator of the progression from acute to chronic colitis in the rat. J Immunol. 2001;166(1):552-558.

Minaiyan M, Ghannadi AR, Etemad, Mahzouni P. A study of the effects of Cydoniao blonga Miller (Quince) on TNBS-induced ulcerative colitis in rats. Res Pharm Sci. 2012;7(2):103-110.

Fornai M, Colucci R, Antonioli L, Ghisu N, Tuccori M, Gori G, et al. Effects of a bicarbonate–alkaline mineral water on digestive motility in experimental models of functional and inflammatory gastrointestinal disorders. Methods Find Exp Clin Pharmacol. 2008;30(4):261-269.

Callahan PM, Cunningham KA. Involvement of 5-HT 2C receptors in mediating the discriminative stimulus properties of m-chlorophenylpiperazine (mCPP). Eur J Pharmacol. 1994;257(1-2):27-38.

Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology. 1989;96(3):795-803.

Motavallian-Naeini A, Minaiyan M, Rabbani M, Mahzuni P. Anti-inflammatory effect of ondansetron through 5HT3 receptors on TNBS-induced coloitis in rat. ECXLI J. 2012;11:30-44.

Motavallian A, Minaiyan M, Rabbani M, Andalib S, Mahzouni P. Involvement of 5HT3 receptors in anti-inflammatory effects of tropisetron on experimental TNBS-induced colitis in rat. Bioimpacts. 2013;3(4):169-176.

Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol. 1982;78(3):206-209.

Lewis JH. The risk of ischaemic colitis in irritable bowel syndrome patients treated with serotonergic therapies. Drug Saf. 2011;34(7):545-565.

Koutroubakis IE. Ischemic colitis: clinical practice in diagnosis and treatment. World J Gastroenterol. 2008;14(48):7302-7308.

Grundy D, Mclean P, Stead R. Impact of 5-HT3 receptor blockade on colonic haemodynamic responses to ischaemia and reperfusion in the rat. Neurogastroenterol Motil. 2007;19(7):607-616.

Painsipp E, Shahbazian A, Holzer P. Alosetron, cilansetron and tegaserod modify mesenteric but not colonic blood flow in rats. Br J Pharmacol. 2009;158(5):1210-1226.

Motavallian A, Minaiyan M, Rabbani M, Mahzouni P, Andalib S, Abed A, et al. Does cisaperide, as a 5HT4 receptor agonist, aggravate the severity of TNBS-induced colitis in rat? Gastroenterol Res Prac. 2012;2012. DOI: 10.1155/2012/362536.

Faerber L, Drechsler S, Ladenburger S, Gschaidmeier H, Fischer W. The neuronal 5-HT3 receptor network after 20 years of research-evolving concepts in management of pain and inflammation. Eur J Pharmacol. 2007;560(1):1-8.

Hassani H, Lucas G, Rozell B, Ernfors P. Attenuation of acute experimental colitis by preventing NPY Y1 receptor signaling. Am J Physiol Gastrointest Liver Physiol. 2005;288(3):G550-G556.


Refbacks

  • There are currently no refbacks.


Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.