Effects of iron and iron chelation in vitro on mucosal oxidant activity inulcerative colitis

Background: Reactive oxygen species may be pathogenic in ulcerative colitis . Oral iron supplements anecdotally exacerbate inflammatory bowel disease a nd iron levels are elevated in the inflamed mucosa, Mucosal iron may enhanc e hydroxyl ion production via Fenton chemistry. Conversely, the iron chelat or, desferrioxamine, is reportedly beneficial in Crohn's disease. Aims: To assess the in vitro effects of exogenous iron and of iron chelator s on the production of reactive oxygen species by colonic biopsies from nor mal control subjects and patients with ulcerative colitis. Methods: Luminol-amplified chemiluminescence was used to measure mucosal re active oxygen species production both before and after addition in vitro of ferric citrate (100 mu M), desferrioxamine (1 mM) and 1,10-phenanthroline (1 mM). Results: Ferric citrate had no effect on the chemiluminescence produced by human colonic mucosa. However, desferrioxamine and phenanthroline reduced c hemiluminescence by 47% (n = 7, P = 0.018) and by 26% (n = 10, P = 0.005), respectively, in inactive ulcerative colitis, and by 44% (n = 9, P = 0.008) and 42% (n = 11, P = 0.006) in active disease. Conclusion: The lack of effect of ferric citrate suggests that sufficient f ree iron is already present in inflamed biopsies to drive the Fenton reacti on maximally. The effects of desferrioxamine and 1,10-phenanthroline on the chemiluminescence of biopsies from patients with ulcerative colitis sugges t that a clinical trial of topical iron chelation in active disease is indi cated.