(HOME) Subject: colitis and iron
Inflamm Bowel Dis 1999 Nov;5(4):253-61
Deferiprone, an oral iron chelator, ameliorates experimental colitis and
gastric ulceration in rats.
Ablin J, Shalev O, Okon E, Karmeli F, Rachmilewitz D
Department of Medicine, Hadassah University Hospital, Mount Scopus,
Israel.
[Medline record in process]
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.
PMID: 10579118, UI: 20046080
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