The effect of memantine on trinitrobenzene sulfonic acid-induced ulcerative colitis in mice

Abstract

Previous reports suggest a significant role for N-Methyl-n-aspartate (NMDA) activation in inflammatory processes. So, this study was conducted to investigate the effect of memantine, a commonly used NMDA receptor antagonist, on inflammatory changes in mice model of colitis. Colitis was induced by intracolonic instillation of trinitrobenzene sulfonic acid (TNBS) (40 mg/kg). Animals received memantine (12.5, 25 and 50 mg/kg, i.p.), glutamate (2 g/kg, p.o.) or dexamethasone (1 mg/kg, i.p.) 24 h before TNBS instillation and daily thereafter for 4 days. The colonic injury was measured by clinical, macroscopic, microscopic, and biochemical analysis. Memantine significantly attenuated the body weight loss, colon weight, the plasma levels of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and colon level of tumor necrosis factor-alpha (TNF-alpha) and myeloperoxidase (MPO); as well as macroscopic and microscopic signs of colitis. Oral administration of glutamate had no significant effect on investigated parameters. Memantine as a NMDA antagonist may provide a novel venue for the development of strategies for the treatment of ulcerative colitis.