Involvement of PPAR in the protective action of tropisetron in an experimental model of ulcerative colitis

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal (GI) tract. Tropisetron, a selective 5-HT3 receptor antagonist, is highly used to counteract chemotherapy-induced emesis. Previous studies revealed the anti-inFLammatory properties of this drug. The aim of this study was to evaluate the role of peroxisome proliferator-activated receptor gamma (PPAR) receptor in the protective effect of tropisetron in an animal model of ulcerative colitis. Experimental colitis was induced by a single intra-colonic instillation of 4% (V/V) acetic acid in male rats. Tropisetron (3mg/kg) and GW9662 (PPAR antagonist) (5mg/kg) were given twice daily for 2 days after colitis induction. Forty-eight hours after induction of colitis, colon was removed and macroscopic and microscopic features were given. Moreover, colonic concentrations of malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor- (TNF-), interleukin-1 (IL-1) levels, myeloperoxidase (MPO), and PPAR activity were assessed. Both macroscopic and histopathological features of colonic injury were markedly ameliorated by tropisetron. Likewise, levels of NO, MDA, TNF-, and IL-1 diminished significantly (p<.05). GW9662 reversed the effect of tropisetron on these markers partially or completely. In addition, tropisetron increased the PPAR and decreased the MPO activity (p<.05). Tropisetron exerts notable anti-inFLammatory effects in acetic acid-induced colitis in rats, which is probably mediated through PPAR receptors.