Granisetron ameliorates acetic acid-induced colitis in rats.

Abstract

Inflammatory bowel disease (IBD) is a chronically relapsing inflammation of the gastrointestinal tract, of which the definite etiology remains ambiguous. Considering the adverse effects and incomplete efficacy of currently administered drugs, it is indispensable to explore new candidates with more desirable therapeutic profiles. 5-HT( 3) receptor antagonists have shown analgesic and anti-inflammatory properties in vitro and in vivo. This study aims to investigate granisetron, a 5-HT( 3) receptor antagonist, in acetic acid-induced rat colitis and probable involvement of 5-HT(3) receptors. Colitis was rendered by instillation of 1 mL of 4% acetic acid (vol/vol) and after 1 hour, granisetron (2 mg/kg), dexamethasone (1 mg/kg), meta-chlorophenylbiguanide (mCPBG, 5 mg/kg), a 5-HT( 3) receptor agonist, or granisetron + mCPBG was given intraperitoneally. Twenty-four hours following colitis induction, animals were sacrificed and distal colons were assessed macroscopically, histologically and biochemically (malondialdehyde, myeloperoxidase, tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6). Granisetron or dexamethasone significantly (p < .05) improved macroscopic and histologic scores, curtailed myeloperoxidase activity and diminished colonic levels of inflammatory cytokines and malondialdehyde. The protective effects of granisetron were reversed by concurrent administration of mCPBG. Our data suggests that the salutary effects of granisetron in acetic acid colitis could be mediated by 5-HT(3) receptors.

• Authors: Gohar Fakhfouri, Reza Rahimian, Ali Daneshmand, Arash Bahremand, Mohammad Reza Rasouli, Ahmad Reza Dehpour, Shahram Ejtemaei Mehr, Kazem Mousavizadeh
• Journal: Human & experimental toxicology (Hum Exp Toxicol) Vol. 29 Issue 4 Pg. 321-8 (Apr 2010) ISSN: 1477-0903 [Electronic] England
• PMID: 20154102 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Biguanides
• Gastrointestinal Agents
• Inflammation Mediators
• Interleukin-1beta
• Interleukin-6
• Receptors, Serotonin, 5-HT3
• Serotonin 5-HT3 Receptor Antagonists
• Serotonin Antagonists
• Serotonin Receptor Agonists
• Tumor Necrosis Factor-alpha
• Malondialdehyde
• Dexamethasone
• 1-(3-chlorophenyl)biguanide
• Peroxidase
• Acetic Acid
• Granisetron

Topics

• Acetic Acid
• Animals
• Anti-Inflammatory Agents (administration & dosage, pharmacology)
• Biguanides (pharmacology)
• Colitis (chemically induced, metabolism, pathology, prevention & control)
• Colon (drug effects, metabolism, pathology)
• Dexamethasone (pharmacology)
• Disease Models, Animal
• Gastrointestinal Agents (administration & dosage, pharmacology)
• Granisetron (administration & dosage, pharmacology)
• Inflammation Mediators (metabolism)
• Injections, Intraperitoneal
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• Male
• Malondialdehyde (metabolism)
• Peroxidase (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Serotonin, 5-HT3 (metabolism)
• Serotonin 5-HT3 Receptor Antagonists
• Serotonin Antagonists (administration & dosage, pharmacology)
• Serotonin Receptor Agonists (pharmacology)
• Tumor Necrosis Factor-alpha (metabolism)