COLONIC ANTIOXIDANT STATUS IN DEXTRAN SULFATE-INDUCED COLITIS IN MICE

Reactive oxygen and nitrogen species have been implicated as mediators of mucosal injury in inflammatory bowel disease (LED), This study inv estigated the status of the endogenous antioxidants and markers of oxi dative mucosal injury in dextran sulfate-induced colitis in mice, Coli tis was induced by supplementing the drinking water with 5% dextran su lfate. After 8 days of dextran treatment, the colonic mucosa was analy zed for total radical scavenging capacity, major lipophilic and aqueou s antioxidants, and thiol-containing markers of oxidative injury. Comp ared with control mucosa, there was a 3.3-fold increase in mucosal mye loperoxidase activity (p < 0.001), corresponding to the neutrophil inf iltration seen histologically. Significant decreases in total peroxyl radical scavenging capacity (15.7%, p < 0.05) and mucosal antioxidant levels, including ubiquinol-9 and ascorbate, were found (53.1 and 17.6 %, respectively, p < 0.001), In contrast, alpha-tocopherol and urate l evels were increased by 63.7 and 109%, respectively (p < 0.001). Glyce raldehyde-3-phosphate dehydrogenase activity, previously shown to be i nactivated by thiol oxidation in inflamed but not in noninflamed IBD e pithelium, and total reduced thiol content were also significantly dec reased by 33.8 and 26.3%, respectively (p < 0.001), These results para llel those reported in IBD mucosal strengthening the relevance of dext ran sulfate-induced colitis in mice to IBD and supporting the use of t his model to provide insights into the pathogenesis of oxidative mucos al injury and the development of novel therapeutic strategies.