title: Involvement of PPARγ in the protective action of tropisetron in an experimental model of ulcerative colitis.
abstract: Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal (GI) tract. Tropisetron, a selective 5-HT3receptor 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 (PPARγ) 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 (3 mg/kg) and GW9662 (PPARγ antagonist) (5 mg/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-α (TNF-α), interleukin-1β (IL-1β) levels, myeloperoxidase (MPO), and PPARγ activity were assessed. Both macroscopic and histopathological features of colonic injury were markedly ameliorated by tropisetron. Likewise, levels of NO, MDA, TNF-α, and IL-1β diminished significantly (p < .05). GW9662 reversed the effect of tropisetron on these markers partially or completely. In addition, tropisetron increased the PPARγ 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 PPARγ receptors.
authors.affiliation: a Department of Pharmacology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.|b Department of Psychiatry and Neuroscience, Faculty of Medicine , Université Laval , Québec City , Québec , Canada.
authors.forename: Reza
authors.initials: R
authors.lastname: Rahimian
authors.affiliation: c Department of Pharmacodynamics and Toxicology, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Zirak
authors.affiliation: d Department of Pharmacology, School of Medicine , Bushehr University of Medical Sciences , Bushehr , Iran.|e Shiraz Neuroscience Research Center , Shiraz University of Medical Sciences , Shiraz , Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Keshavarz
authors.affiliation: f Brain and Spinal Cord Injury Research Center, Neuroscience Institute , Tehran University of Medical Sciences Tehran , Tehran , Iran.
authors.forename: Nahid
authors.initials: N
authors.lastname: Fakhraei
authors.affiliation: g Pharmaceutical Sciences Research Center, School of Pharmacy , Kermanshah University of Medical Sciences , Kermanshah , Iran.|h Department of Pharmacology, Toxicology and Medical Services, School of Pharmacy , Kermanshah University of Medical Sciences , Kermanshah , Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Mohammadi-Farani
authors.affiliation: i Cellular and Molecular Research Center and Department of Molecular Medicine , Faculty of Advanced Technologies in Medicine Iran University of Medical Sciences , Tehran , Iran.
authors.forename: Hanan
authors.initials: H
authors.lastname: Hamdi
authors.affiliation: i Cellular and Molecular Research Center and Department of Molecular Medicine , Faculty of Advanced Technologies in Medicine Iran University of Medical Sciences , Tehran , Iran.
authors.forename: Kazem
authors.initials: K
authors.lastname: Mousavizadeh
keywords: 5-HT receptor; PPARγ; Tropisetron; rat; ulcerative colitis