Colonic antioxidant status in dextran sulfate-induced colitis in mice.

SUMMARY: : Reactive oxygen and nitrogen species have been implicated as mediators of mucosal injury in inflammatory bowel disease (IBD). This study investigated the status of the endogenous antioxidants and markers of oxidative mucosal injury in dextran sulfate-induced colitis in mice. Colitis was induced by supplementing the drinking water with 5% dextran sulfate. After 8 days of dextran treatment, the colonic mucosa was analyzed for total radical scavenging capacity, major lipophilic and aqueous antioxidants, and thiol-containing markers of oxidative injury. Compared with control mucosa, there was a 3.3-fold increase in mucosal myeloperoxidase activity (p < 0.001), corresponding to the neutrophil infiltration 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, α-tocopherol and urate levels were increased by 63.7 and 109%, respectively (p < 0.001). Glyceraldehyde-3-phosphate dehydrogenase activity, previously shown to be inactivated by thiol oxidation in inflamed but not in noninflamed IBD epithelium, and total reduced thiol content were also significantly decreased by 33.8 and 26.3%, respectively (p < 0.001). These results parallel those reported in IBD mucosa, strengthening the relevance of dextran sulfate-induced colitis in mice to IBD and supporting the use of this model to provide insights into the pathogenesis of oxidative mucosal injury and the development of novel therapeutic strategies.