THE ANTIOXIDANT PROPERTIES OF 5-AMINOSALICYLIC ACID

Oxidative damage to biological membranes is an important cause of tiss ue injury in inflammatory bowel disease. 5-Aminosalicylic Acid (5ASA) has therapeutic efficacy in Ulcerative colitis, which may be based on its antioxidant properties. We used Parinaric acid as a fluorescent ma rker of oxidation in an intestinal microvillous brush border membrane preparation. Various concentrations of the antioxidants 5ASA, ascorbat e, and tocopherol were added, and oxidation was initiated from within the membrane by 2,2' azobis (2,4-dimethylvaleronitrile) (AMVN) and fro m solution by 2,2' azobis (2-amidinopropane) hydrochloride (AAPH). Toc opherol was able to inhibit oxidation from either source. Ascorbate wa s only able to inhibit oxidation initiated from solution. 5ASA was abl e to inhibit oxidation initiated from either site, and was more effect ive than tocopherol against AAPH, but similarly effective against AMVN . We postulate that water soluble 5ASA preferentially associates with the membrane surface, allowing chain-breaking antioxidant activity whe n peroxidation is initiated within the membrane. Likewise, it is effec tive against aqueous oxidants because its position allows it to intera ct with AAPH before lipid peroxidation can be initiated as well as bre aking the lipid peroxidation chain once it is initiated. This dual cap acity may be important for therapeutic effect of 5ASA and may suggest other candidate antioxidants for clinical trials.