Deferiprone, an oral iron chelator, ameliorates experimental colitis and gastric ulceration in rats

Iron is pivotal in producing tissue-damaging reactive oxygen metabolites. O ur aim is to determine the antiinflammatory activity of deferiprone, an ora l iron chelator, in experimental colitis and gastritis. Colitis was induced by intraceccal administration of 2 mi 5% acetic acid or by intracolonic ad ministration of 0.1 mi 3% iodoacetamide, with or without cotreatment with d eferiprone. Gastritis was induced by intragastric administration of ethanol or hydrochloric acid (HCl) and by subcutaneous injection of indomethacin, with and without deferiprone. Rats were killed 24 hours after acetic acid a nd iodoacetamide, 30 minutes after ethanol, one hour after HCl, and three h ours after indomethacin administration. The colon or stomach was isolated, macroscopic damage was measured, and mucosal samples were obtained for dete rmination of eicosanoid generation, myeloperoxidase (MPO), and nitric oxide synthase (NOS) activities. Deferiprone decreased iodoacetamide and acetic acid-induced macroscopic colonic damage by 67% and 69%, respectively, and m acroscopic gastric damage by 91%, 68%, and 46% induced by ethanol, HCl, and indomethacin, respectively. The effect of deferiprone was accompanied by s ignificant decrease in colonic and gastric, MPO and NOS activities, and col onic prostaglandin E-2 (PGE(2)) generation, in acetic acid, ethanol, and in domethacin models, whereas in the iodoacetamide and HCl models attenuation of the decrease in PGE, generation was seen. Deferiprone is protective in e xperimental colitis and gastritis, probably due to decreased production of iron-dependent oxygen-free radicals. Oral iron chelators may constitute a n ovel approach to ameliorate gastrointestinal inflammatory disorders.