Protective effect of dizocilpine (MK-801) on TNBS-induced experimental colitis in mice

Document Type: Research article

Authors

1 Department of Pharmacology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

2 Department of Clinical Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Abstract

Ulcerative colitis is chronic and recurrent disease of the gastrointestinal tract with uncertain etiology and incomplete treatment options. N-methyl-d-aspartate (NMDA) receptor suppression has shown anti-inflammatory effects in vitro and in vivo. The aim of present study was to evaluate the role of dizocilpine (MK-801), a noncompetitive NMDA receptor antagonist, on TNBS (trinitrobenzene sulfonic acid)-induced murine model of colitis. Dizocilpine (0.1, 1 and 5 mg/kg) was given to mice intraperitoneally from 24 hours before induction of colitis and daily thereafter for 4 days. Dexamethasone (1 mg/kg) was used as the reference drug. Colitis was induced by intracolonic administration of TNBSof TNBS/Ethanol (50/50 v/v, 40mg/kg). Animals were sacrificed 5 days after colitis induction and distal colons were examined macroscopically and microscopically. The colonic tissue level of pro-inflammatory cytokines including interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were assessed by ELISA. Myeloperoxidase (MPO) level was also measured in colon. Dizocilpine, particularly with intermediate dose of 1mg/kg significantly improved animal’s weight loss as well as macroscopic and microscopic signs of colitis, reduced colonic levels of IL-1β, IL-6, TNF-α and MPO activity. Hence, dizocilpine has significant protective effects in TNBS- induced colitis and NMDA suppression may be a new and effective therapeutic strategy in ulcerative colitis via decreasing in pro-inflammatory cytokine production.

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