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224 ORAL SUPPLEMENTATION OF N-ACETYL GLUCOSAMINE REDUCES INDOMETHACIN-INDUCED INTESTINAL INFLAMMATION M Klompus, A Shafer, Q Tejpar, K Madsen, RN Fedorak BACKGROUND: N-acetyl-glucosamine (NAG), a natural occurring amino-sugar, is a metabolic fuel for fibroblast and epithelial glycosaminoglycans (GAG) synthesis. GAG in turn becomes a key element in forming the extracellular connective tissue matrix which maintains the integrity of the epithelial barrier. NAG has been shown to enhance GAG synthesis and subsequently connective tissue matrices. During inflammatory bowel disease and intestinal injury, activated macrophages breakdown GAG leading to a degradation of the connective tissue matrix.
Division of Gastroenterology, University of Alberta, Edmonton, Alberta
OBJECTIVE: Using an experimental model of intestinal injury, we examined whether oral administration of supplemental NAG would enhance GAG synthesis and lead to attenuation of the intestinal inflammatory response and accelerated healing.
METHODS: Mice were pre-treated for 5d (study day -5 to 0) and then for 13 additional days (study day 0 to 13) with varying concentrations (0.2mg/kg, 2mg/kg, 20mg/kg or placebo) of NAG in their drinking water. Intestinal injury was induced by indomethacin (8mg/kg/d) via oral gavage for 3d (study days 0 to 2). On study day 13, mice were sacrificed and upper and lower small intestine (SI) assessed for intestinal injury and inflammation via myeloperoxidase (MPO) levels.
RESULTS: Administration of NAG (20mg/kg) reduced indomethacin-induced MPO elevation in both the upper and lower SI when compared to placebo-treated control mice (86.90±7.3 vs 2991.1±1021.7 for upper SI and 155.8±37.4 vs 2493.7±559.4 for lower SI, respectively). Administration of NAG at 2.0 mg/kg/d demonstrated a dose-dependent reduction in MPO, while 0.2mg/kg/d was no different than placebo in reducing indomethacin-induced injury.
CONCLUSION: The natural occurring amino-sugar, NAG, when administered orally attenuates the severity of indomethacin-induced injury in a dose-dependent fashion. NAG represents a potential novel therapy for prevention and treatment of intestinal inflammation.