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50 N-ACETYL GLUCOSAMINE ATTENUATES COLITIS IN AN EXPERIMENTAL MODEL OF COLITIS A Shaefer, M Klompus, K Madsen, RN Fedorak BACKGROUND: N-acetyl-glucosamine (NAG), a naturally occurring aminosugar, is a metabolic fuel for fibroblast and epithelial glycosaminoglycan (GAG) synthesis. GAG in turn is a key element in the formation of extracellular connective tissue matrix which maintains the integrity of the epithelial barrier. During active inflammation in the gut, activated macrophages break down GAG, leading to a degradation of the connective tissue matrix. Administration of NAG has been shown to enhance GAG synthesis.
Division of Gastroenterology, University of Alberta, Edmonton, Alberta
OBJECTIVE: Using an experimental animal model of colitis, we examined whether oral administration of supplemental NAG would enhance GAG synthesis and lead to attenuation of the inflammatory response and accelerated healing of colitis.
METHODS: Mice were pretreated for seven days (study days 0 to 7) with orally gavaged NAG (8 mg/kg) or placebo. Colitis was then induced with a seven day (study days 8 to 14) administration of 4.5% dextran sulphate (DSS) in the drinking water. Mice continued to receive NAG or placebo for the entire duration of the study. On study day 14, DSS was removed and the animals observed for an additional five days (study days 15 to 19). Disease activity index (DAI) score (maximum=12; minimum=0) was determined daily using a combined index consisting of: (1) % body weight loss; (2) stool consistency; and (3) fecal occult blood. At the termination of the study, mice were sacrificed for histological injury scoring, and mucosal cytokine analysis.
RESULTS: Mice receiving DSS developed colitis that increased in severity daily, reaching a maximum DAI of 9.0±0.8 on day 15. Removal of DSS resulted in a return of the DAI to baseline within five days. Mice receiving NAG had significantly reduced colitis, as evidenced by a decrease in the maximum DAI at day 15 (7.1±0.2; P<0.05 compared with placebo) as well as a quicker recovery (P<0.05). In addition, mice treated with NAG demonstrated a reduced level of IFN
CONCLUSION: The natural occurring aminosugar, NAG, when administered orally, significantly attenuates DSS-induced colitis in mice and reduces the mucosal proinflammatory cytokine profile.