Deferiprone, an oral iron chelator, ameliorates experimental colitis and gastric ulceration in rats.
Iron is pivotal is producing tissue-damaging reactive oxygen metabolites. Our aim is to determine the antiinflammatory activity of deferiprone, an oral iron chelator, in experimental colitis and gastritis. Colitis was induced by intraceccal administration of 2 ml 5% acetic acid or by intracolonic administration of 0.1 ml 3% iodoacetamide, with or without cotreatment with deferiprone. 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 and iodoacetamide, 30 minutes after ethanol, one hour after HCl, and three hours after indomethacin administration. The colon or stomach was isolated, macroscopic damage was measured, and mucosal samples were obtained for determination 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 macroscopic gastric damage by 91%, 68%, and 46% induced by ethanol, HCl, and indomethacin, respectively. The effect of deferiprone was accompanied by significant decrease in colonic and gastric, MPO and NOS activities, and colonic prostaglandin E2 (PGE2) generation, in acetic acid, ethanol, and indomethacin models, whereas in the iodoacetamide and HCl models attenuation of the decrease in PGE2 generation was seen. Deferiprone is protective in experimental colitis and gastritis, probably due to decreased production of iron-dependent oxygen-free radicals. Oral iron chelators may constitute a novel approach to ameliorate gastrointestinal inflammatory disorders.
Ablin
J
J
Department of Medicine, Hadassah University Hospital, Mount Scopus, Israel.
Shalev
O
O
Okon
E
E
Karmeli
F
F
Rachmilewitz
D
D
D000085:Acetates; D000284:Administration, Oral; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000150:complications*; D000077543:Deferiprone; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D005756:Gastritis / Q000139:chemically induced / Q000150:complications*; D007213:Indomethacin; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007460:Iodoacetamide; D007502:Iron Chelating Agents / Q000008:administration & dosage*; D008297:Male; D011728:Pyridones / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D016896:Treatment Outcome
D000085:Acetates; D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D007213:Indomethacin; D007460:Iodoacetamide