Efficacy of use of colonoscopy in dextran sulfate sodium induced ulcerative colitis in rats: the evaluation of the effects of antioxidant by colonoscopy

摘要

The goals in developing animal models of inflammatory bowel disease (IBD) are to determine the underlying mechanisms and the action of currently available drugs and to evaluate the value of new therapeutic approaches. Because of the difficulty in determining the severity of colitis in living animals, it has been necessary to kill the experimental animals at varying stages in the studies. If colonoscopic evaluation or endoscopic biopsy is feasible in these experimental animals, continuous observations could be possible, thus avoiding the need to kill them. The aims of the current study were to assess the efficacy of endoscopic examination as a monitoring tool for the severity of colitis in rats and to the efficacy of DA-9601, an extract from Artemisia asiatica which has both antioxidative and cytoprotective actions, on dextran sulfate sodium induced ulcerative colitis in rats endoscopically. Sprague-Dawley rats received 4% DSS in drinking water for 5 consecutive days. Either DA-9601 or sulfasalazine was administered twice a day for 8 days, starting 3 days before DSS administration. After the colonoscopic evaluations on days 2, 4, and 5 after DSS administration the rats were also killed for gross and histopathological evaluations. Simultaneous measurements of malondialdehyde (MDA) and myeloperoxidase (MPO) activities were performed. There was a statistically significant correlation between the scores evaluated by the gross examination and colonoscopic scores, between the colonoscopic scores and the levels of MDA or mucosal MPO activities, and between colonoscopic scores and histopathological activity index. DA-9601 showed excellent improvement in gross lesion scores, decreased MDA amounts and MPO activities compared to sulfasalazine. In conclusion, the introduction of appropriate colonoscopic examination in animal models of IBD could avoid the sacrifice of experimental animals for interim evaluation and provide the valuable information on the course and efficacy of treatment. The potential usefulness of antioxidants in treating IBD is very promising based on the colonoscopic intervention of IBD.