Involvement of PPARγin 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-HT 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 (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.

Protective Effects of Honey and Spirulina Platensis on Acetic Acid-Induced Ulcerative Colitis in Rats

“…In UC, the overproduction of IL-1β, IL-8, IL-6, and PGE2 causes epithelial cell necrosis and edema (27).…”

5-HT3Receptor Antagonists in Neurologic and Neuropsychiatric Disorders: The Iceberg Still Lies beneath the Surface

“…Tropisetron attenuates gut inflammation through PPARg induction after rectal acetic acid instillation. The protective effect is diminished in the presence of PPARg receptor antagonist GW9662 (Rahimian et al, 2016). The same mechanism could underpin the action of 5-HT 3 R antagonists in cerebral ischemia models, since the PPARg agonist pioglitazone leads to a prominent improvement in transient middle cerebral artery occlusion in rats (Deplanque et al, 2003;Shimazu et al, 2005;Sundararajan et al, 2005;Bordet et al, 2006a).…”

“…As stated in section IV.F, 5-HT 3 R antagonism can induce PPARg transcriptional activity (Rahimian et al, 2016). This effect has an established antidepressive outcome in both animal and human studies (Eissa Ahmed et al, 2009;Sepanjnia et al, 2012).…”

“…observation points out the involvement of 5-HT 3 Rs in tropisetron-induced insulin secretion. In vivo, tropisetron has been shown to induce PPARg transcriptional activity and to be beneficial in cerulein-induced acute pancreatitis in mice (Rahimian et al, 2016(Rahimian et al, , 2017. These effects highlight the ability of 5-HT 3 R antagonists in regulating blood glucose levels.…”

“…In addition to facilitation of cholinergic transmission and NO signaling, 5-HT 3 R antagonists can rescue cognition through various mechanisms, including antiinflammatory effects (e.g., inhibition of nuclear factor-kB), induction of peroxisome proliferator-activated receptor g (PPARg) transcriptional activity (see section IV.F), and attenuation of calcium signaling (Rahimian et al, 2013b(Rahimian et al, , 2016. Therefore, they hold great promise as a new therapeutic approach for memory impairments with complex etiopathology such as AD (for more details, see Fakhfouri et al, 2012Fakhfouri et al, , 2015.…”