EVALUATING THE ANTIOXIDANT POTENTIAL OF NEW TREATMENTS FOR INFLAMMATORY BOWEL-DISEASE USING A RAT MODEL OF COLITIS

Background-Reactive oxygen species may mediate tissue injury in inflam matory bowel disease. Aminosalicylates have antioxidant activity and t he antioxidants, superoxide dismutase and allopurinol, are of reported benefit in inflammatory bowel disease. Aim-To develop a convenient te chnique for testing the antioxidant potential of standard and novel th erapeutic agents for use in inflammatory bowel disease. Methods-Amplif ied chemiluminescence was used to measure reactive species production by colonic specimens from rats with acetic acid induced colitis and to assess the in vitro effect of conventional antioxidants, standard the rapies and proposed novel therapies for inflammatory bowel disease. Re sults-The model was validated by demonstrating that the profile of eff ects on chemiluminescence of acetic acid induced colitis biopsy specim ens given by conventional antioxidants (sodium azide, catalase, copper -zinc superoxide dismutase, dimethyl sulphoxide, N-acetylcysteine and ascorbate) and standard therapies (5-aminosalicylate and hydrocortison e) resembled that previously reported using biopsy specimens from ulce rative colitis. Human recombinant manganese superoxide dismutase did n ot alter chemiluminescence. Two novel compounds, LY231617 (10 mM) and amflutizole (20 mM), reduced chemiluminescence by 98% (n=5, p=0.009) a nd 88% (n=5, p=0.03), respectively. Conclusions-The similarity of the chemiluminescence responses of colonic biopsy specimens from acetic ac id induced colitis and ulcerative colitis to a range of conventional a ntioxidants and standard treatments suggests that this model is a usef ul method for testing the antioxidant potential of new therapies for i nflammatory bowel disease. The antioxidant actions of dimethyl sulphox ide, ascorbate, and the novel compounds, amflutizole and LY231617 in t his model suggest that these agents merit further assessment in the tr eatment of inflammatory bowel disease.