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Anti‐inflammatory effects of 5‐HT 3 receptor antagonist, tropisetron on experimental colitis in rats
Author(s) -
Mousavizadeh K.,
Rahimian R.,
Fakhfouri G.,
Aslani F. S.,
Ghafourifar P.
Publication year - 2009
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2009.02102.x
Subject(s) - tropisetron , colitis , malondialdehyde , dexamethasone , pharmacology , myeloperoxidase , medicine , inflammatory bowel disease , oxidative stress , proinflammatory cytokine , inflammation , antagonist , receptor , disease
Background 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. Materials and methods 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‐1β, interleukin‐6 and tumour necrosis factor‐α levels and oxidative stress markers myeloperoxidase (MPO) and malondialdehyde (MDA) in colonic tissues. Results 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. Conclusions Tropisetron exert beneficial effects in experimental rat colitis and therefore might be useful in the treatment of IBD.