DEPLETED MUCOSAL ANTIOXIDANT DEFENSES IN INFLAMMATORY BOWEL-DISEASE

Experimental approaches designed to define the role of reactive oxygen and nitrogen species generated by inflammatory cells in the tissue in jury seen in inflammatory bowel disease rarely consider the chemical a ntioxidant defences against such increased oxidant stress in the mucos a. In this investigation, we have analysed components of the aqueous a nd lipid phase antioxidant mucosal defences by measuring the total per oxyl radical scavenging capacity and the levels of urate, glutathione, alpha-tocopherol, and ubiquinol-10 in paired noninflamed and inflamed mucosal biopsies from inflammatory bowel disease patients. Compared t o paired noninflamed mucosa, decreases were observed in inflamed mucos a for total peroxyl radical scavenging capacity (55%, p = 0.0031), ura te [Crohn's disease (CD), 62.2%, p = 0.066; ulcerative colitis (UC), 4 7.38, p = 0.031], glutathione (UC, 59%, 7/8 patients, ns), total gluta thione (UC 65.2%, 6/8 patients, ns), ubiquinol-10 (CD, 75.7%, p = 0.03 ; UC, 90.5%, p = 0.005). The mean alpha-tocopherol content was unchang ed. These observations support our earlier findings of decreased reduc ed and total ascorbic acid in inflamed IBD mucosa and demonstrate that the loss of chemical antioxidant defences affects almost all the majo r components. The decreased antioxidant defences may severely compromi se the inflamed mucosa, rendering it more susceptible to oxidative tis sue damage, hindering recovery of the mucosa and return of epithelial cell layer integrity. The loss of chemical antioxidant components prov ides a strong rationale for developing novel antioxidant therapies for the treatment of inflammatory bowel disease.