Millar A D, Rampton D S, Blake D R
The Gastrointestinal Science, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK.
Aliment Pharmacol Ther. 2000 Sep;14(9):1163-8. doi: 10.1046/j.1365-2036.2000.00828.x.
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.
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.
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).
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.
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.
活性氧可能在溃疡性结肠炎中具有致病性。口服铁补充剂据传闻会加重炎症性肠病,且炎症黏膜中的铁水平会升高。黏膜铁可通过芬顿化学反应增强羟离子的产生。相反,据报道铁螯合剂去铁胺对克罗恩病有益。
评估外源性铁和铁螯合剂对正常对照受试者及溃疡性结肠炎患者结肠活检组织中活性氧产生的体外影响。
使用鲁米诺增强化学发光法测量在体外添加柠檬酸铁(100微摩尔)、去铁胺(1毫摩尔)和1,10 - 菲啰啉(1毫摩尔)前后黏膜活性氧的产生。
柠檬酸铁对人结肠黏膜产生的化学发光没有影响。然而,在非活动期溃疡性结肠炎中,去铁胺和菲啰啉分别使化学发光降低了47%(n = 7,P = 0.018)和26%(n = 10,P = 0.005),在活动期疾病中分别降低了44%(n = 9,P = 0.008)和42%(n = 11,P = 0.006)。
柠檬酸铁无作用表明炎症活检组织中已存在足够的游离铁以最大程度驱动芬顿反应。去铁胺和1,10 - 菲啰啉对溃疡性结肠炎患者活检组织化学发光的影响表明,有必要对活动期疾病进行局部铁螯合的临床试验。