ALTERED ASCORBIC-ACID STATUS IN THE MUCOSA FROM INFLAMMATORY BOWEL-DISEASE PATIENTS

Attempts to establish the presence of oxidant stress and tissue damage in inflammatory bowel disease (IBD) have relied on determining the ca pacity of peripheral blood inflammatory cells to produce reactive oxyg en species (ROS) and other indirect indices. These approaches have fai led to address whether or not there are adequate chemical antioxidant defences to prevent oxidative injury in the inflamed mucosa. In this i nvestigation we have determined the mucosal concentrations of reduced and total ascorbic acid and the redox status in paired non-inflamed an d inflamed mucosa using colonic biopsies from IBD patients. In inflame d mucosa from Crohn's disease (CD) patients, reduced and total ascorbi c acid content decreased by 35% (p = 0.014 and p = 0.009, respectively ). In ulcerative colitis (UC) patients, mucosal total ascorbic acid co ntent decreased by 73% (p = 0.069) and reduced ascorbic acid by 41% (p = 0.014). The proportion of total ascorbic acid present in its reduce d form in histologically normal mucosa from CD patients was unusually low at similar to 30%. In the paired-inflamed mucosa from CD patients, the redox ratio was also similar to 30% despite the loss of 35% of to tal ascorbate. In UC patients, the ascorbate redox ratio in the non-in flamed mucosa was 23% which increased to 51% in paired inflamed mucosa . This increase reflected the loss (73%) of total ascorbate. Reduction of dehydroascorbic acid by GSH/NADPH dependent dehydroascorbic acid r eductase decreased significantly (p = 0.046) in inflamed mucosa from U C patients, suggesting that the capacity of the inflamed mucosa to mai ntain the concentration of reduced ascorbic acid is also diminished. H PLC analysis of mucosal preparations for diketogulonic acid, the decom position product of dehydroascorbic acid, did not account for the loss of total ascorbate in the inflamed mucosa suggesting that ascorbate e quivalents underwent further decomposition reactions or were excreted to the colonic lumen. We conclude that the normal luminal environment is strongly oxidising in character and that oxidant stress derived fro m inflammatory cells contributes to the loss of 35-73% total and reduc ed ascorbate. In absolute terms, the overall loss of this antioxidant buffering capacity would decrease the capacity of the inflamed mucosa to prevent oxidative tissue damage and hinder recovery of the inflamed mucosa.