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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