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A new insight into redox mechanisms of cysteamine‐induced duodenal ulcers
Author(s) -
Khomenko Tetyana,
Bernstein Joanna,
Osapay Klara,
Osapay George,
McLaren Gordon D.,
Said Hamid M.,
Szabo Sandor
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1084-c
Subject(s) - cysteamine , duodenum , deferoxamine , chemistry , jejunum , redox , medicine , incubation , intestinal mucosa , biochemistry , endocrinology , inorganic chemistry
Cysteamine (C) (HS‐CH2‐CH2‐NH2) is a reducing aminothiol which may react with transition metals to generate H 2 O 2 . C specifically induces ulcers in rat proximal duodenum where most dietary iron absorption takes place. We hypothesized that iron may play a role in redox reactions involved in the pathogenesis of C‐induced duodenal ulcers (DU). In rats, using oxygen and redox electrodes we detected a decrease in both oxygen concentration and redox potential in the proximal duodenum at 2 and 12 hr after administration of C (25 mg/100 g, p.o.). A detectable level of C was found by HPLC assay in duodenal mucosa (0.018 ug/mg wet weight) and 4 fold less in gastric mucosa but not in jejunum, colon or liver 2 hr after C administration. Rats fed an iron‐deficient diet for 6 weeks had a 34% decrease in iron concentration in the duodenal mucosa, accompanied by a 6.6 fold decrease in C‐induced DU size. Pretreatment of rats with Fe 3+ or Fe 2+ aggravated DU, whereas iron depletion by deferoxamine decreased DU by 38%. [C14]C uptake by isolated duodenal, gastric, jejunal and colonic enterocytes, and by IEC‐6 and Caco‐2 cells increased linearly with time (up to 15 min). [C14]C uptake was pH dependent, with higher uptake in more alkaline buffer. Unlabeled C (1 mM) markedly inhibited [C14]C uptake by all cells. Overloading IEC‐6 with iron (100 uM for 1 hr) accelerated uptake of [C14]C by 40%, but incubation of cells with deferoxamine (100 or 200 uM for 24 hr) inhibited C uptake by 30% and 61%, respectively. These findings suggest a role for iron‐catalyzed redox reactions in the pathogenesis of C‐induced organ‐specific tissue injury.