Effects of iron and iron chelation in vitro on mucosal oxidant activity in ulcerative colitis.
BACKGROUND
Reactive oxygen species may be pathogenic in ulcerative colitis. Oral iron supplements anecdotally exacerbate inflammatory bowel disease and iron levels are elevated in the inflamed mucosa. Mucosal iron may enhance hydroxyl ion production via Fenton chemistry. Conversely, the iron chelator, desferrioxamine, is reportedly beneficial in Crohn's disease.


OBJECTIVE
To assess the in vitro effects of exogenous iron and of iron chelators on the production of reactive oxygen species by colonic biopsies from normal control subjects and patients with ulcerative colitis.


METHODS
Luminol-amplified chemiluminescence was used to measure mucosal reactive oxygen species production both before and after addition in vitro of ferric citrate (100 microM), 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 chemiluminescence 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.


CONCLUSIONS
The lack of effect of ferric citrate suggests that sufficient free iron is already present in inflamed biopsies to drive the Fenton reaction maximally. The effects of desferrioxamine and 1,10-phenanthroline on the chemiluminescence of biopsies from patients with ulcerative colitis suggest that a clinical trial of topical iron chelation in active disease is indicated.
Millar
A D
AD
The Gastrointestinal Science, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK.
Rampton
D S
DS
Blake
D R
DR
D000328:Adult; D000368:Aged; D002614:Chelating Agents / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism*; D003676:Deferoxamine / Q000627:therapeutic use*; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D010618:Phenanthrolines / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D002614:Chelating Agents; D005290:Ferric Compounds; D010618:Phenanthrolines; D017382:Reactive Oxygen Species; C025314:ferric citrate; D003676:Deferoxamine