tropisetron and Colitis

Ulcerative colitis (UC) involves chronic inflammation of the large intestine. Several agents are used to treat UC, but adverse side effects are remaining problems. We examined the effect of tropisetron as a new type of drug for UC using a dextran sulfate sodium (DSS)-induced model of colitis in mice. We developed a DSS-induced model of colitis and calculated the Disease Activity Index and colon length. We measured myeloperoxidase activity and determined the protein level and mRNA level of cytokines in the colon. DSS-induced colitis was ameliorated by administration of tropisetron and PNU282987. Pre-administration of methyllycaconitine diminished the suppressive effect of tropisetron upon DSS-induced colitis. These findings suggested that α7 nicotinic acetylcholine receptors (α7 nAChRs) were related to the suppressive effect of tropisetron on DSS-induced colitis. Additionally, stimulation of α7 nAChRs decreased the colon level of interleukin-6 and interferon-γ upon DSS administration. Furthermore, stimulation of α7 nAChRs decreased macrophage infiltration, with expression of α7 nAChR increased by DSS administration. These results suggest that the underlying mechanism of this suppressive effect on DSS-induced colitis is via stimulation of α7 nAChRs and involves suppression of expression of pro-inflammatory cytokines. Tropisetron could be a new type of therapeutic agent for UC.

Topics: Aconitine; alpha7 Nicotinic Acetylcholine Receptor; Animals; Colitis; Colitis, Ulcerative; Colon; Cytokines; Dextran Sulfate; Disease Models, Animal; Indoles; Inflammation Mediators; Male; Mice, Inbred ICR; Peroxidase; Tropisetron

There is a pressing need for research that will lead to the development of new therapeutic approaches for treating inflammatory bowel disease (IBD). The aim of this study was to investigate the effects of tropisetron, a 5-Hydroxytryptamine (5-HT)-3 receptor antagonist with anti-inflammatory properties in a model of experimental colitis in rat.. Acetic acid model of colitis in rats was used. Colitis was induced by intracolonal instillation of 4% (v/v) acetic acid. One hour after induction of colitis, intraperitoneal (IP) or intrarectal (IR) tropisetron (2 mg kg(-1), either route) or dexamethasone (1 mg kg(-1), either route) was administered. The severity of colitis was assessed 24 h later using macroscopic and microscopic changes of damaged colon, measurement of inflammatory cytokines interleukin-1beta, interleukin-6 and tumour necrosis factor-alpha levels and oxidative stress markers myeloperoxidase (MPO) and malondialdehyde (MDA) in colonic tissues.. Tropisetron decreased colonic macroscopic and microscopic damage scores. This was associated with significant reduction in both neutrophil infiltration indicated by decreased colonic MPO activity and lipid peroxidation measured by MDA content, as well as a decreased colonic inflammatory cytokines. IR tropisetron decreased colonic damage that was associated with decreased neutrophil infiltration, lipid peroxidation and colonic inflammatory cytokines. Beneficial effects of tropisetron were lower than those of dexamethasone. No significant differences were observed between IP and IR administration with the exception of MDA level more diminished by IP tropisetron and dexamethasone.. Tropisetron exert beneficial effects in experimental rat colitis and therefore might be useful in the treatment of IBD.

Topics: Animals; Anti-Inflammatory Agents; Colitis; Indoles; Male; Models, Animal; Rats; Rats, Sprague-Dawley; Serotonin Antagonists; Statistics as Topic; Tropisetron