Granisetron ameliorates acetic acid-induced colitis in rats.
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.
Department of Pharmacology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Gohar
G
Fakhfouri
Reza
R
Rahimian
Ali
A
Daneshmand
Arash
A
Bahremand
Mohammad Reza
MR
Rasouli
Ahmad Reza
AR
Dehpour
Shahram Ejtemaei
SE
Mehr
Kazem
K
Mousavizadeh
D019342:Acetic Acid; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001645:Biguanides / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017829:Granisetron / Q000008:administration & dosage / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D019342:Acetic Acid; D000893:Anti-Inflammatory Agents; D001645:Biguanides; D003907:Dexamethasone; D005765:Gastrointestinal Agents; D017829:Granisetron; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008315:Malondialdehyde; D009195:Peroxidase; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014409:Tumor Necrosis Factor-alpha; C065734:1-(3-chlorophenyl)biguanide