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We show here that cysteamine-induced ulceration was aggravated by pretreatment of rats with Fe<jats:sup>3+<\/jats:sup>or Fe<jats:sup>2+<\/jats:sup>compounds, which elevated iron concentration in the duodenal mucosa. In contrast, feeding rats an iron-deficient diet was associated with a 4.6-fold decrease in ulcer formation, accompanied by a 34% decrease ( P &lt; 0.05) in the duodenal mucosal iron concentration. Administration of deferoxamine inhibited ulceration by 65%. We also observed that the antiulcer effect of H2 receptor antagonist cimetidine included a 35% decrease in iron concentration in the duodenal mucosa. Cysteamine-induced duodenal ulcers were also decreased in iron-deficient Belgrade rats ( P &lt; 0.05). In normal rats, cysteamine administration increased the iron concentration in the proximal duodenal mucosa by 33% in the preulcerogenic stage but at the same time decreased serum iron ( P &lt; 0.05). Cysteamine also enhanced activation of mucosal iron regulatory protein 1 and increased the expression of divalent metal transporter 1 mRNA and protein. Transferrin receptor 1 protein expression was also increased, although mucosal ferroportin and ferritin remained almost unchanged. These results indicate an expansion of the intracellular labile iron pool in the duodenal mucosa, increasing its susceptibility to oxidative stress, and suggest a role for iron in the pathogenesis of organ-specific tissue injury such as duodenal ulcers.<\/jats:p>","DOI":"10.1152\/ajpgi.90257.2008","type":"journal-article","created":{"date-parts":[[2009,4,3]],"date-time":"2009-04-03T01:41:44Z","timestamp":1238722904000},"page":"G1277-G1286","source":"Crossref","is-referenced-by-count":24,"title":["Role of iron in the pathogenesis of cysteamine-induced duodenal ulceration in rats"],"prefix":"10.1152","volume":"296","author":[{"given":"Tetyana","family":"Khomenko","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandor","family":"Szabo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoming","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory J.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordon D.","family":"McLaren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010635820071"},{"key":"R2","doi-asserted-by":"crossref","unstructured":"Adler RS, Gallagher GT, Szabo S.Duodenal ulcerogens cysteamine and propionitrile decrease duodenal neutralization of acid in the rat.Dig Dis Sci288: 716\u2013723, 1983.","DOI":"10.1007\/BF01312562"},{"key":"R3","unstructured":"Anderson GJ, Vulpe CD.Regulation of intestinal iron transport. 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