RGD Reference Report - Role of iron in the pathogenesis of cysteamine-induced duodenal ulceration in rats. - Rat Genome Database

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Role of iron in the pathogenesis of cysteamine-induced duodenal ulceration in rats.

Authors: Khomenko, T  Szabo, S  Deng, X  Ishikawa, H  Anderson, GJ  McLaren, GD 
Citation: Khomenko T, etal., Am J Physiol Gastrointest Liver Physiol. 2009 Jun;296(6):G1277-86. doi: 10.1152/ajpgi.90257.2008. Epub 2009 Apr 2.
RGD ID: 11541091
Pubmed: PMID:19342511   (View Abstract at PubMed)
PMCID: PMC3834006   (View Article at PubMed Central)
DOI: DOI:10.1152/ajpgi.90257.2008   (Journal Full-text)

Cysteamine induces perforating duodenal ulcers in rats within 24-48 h. This reducing aminothiol generates hydrogen peroxide in the presence of transition metals (e.g., ferric iron), producing oxidative stress, which may contribute to organ-specific tissue damage. Since most intestinal iron absorption takes place in the proximal duodenum, we hypothesized that cysteamine may disrupt regulation of mucosal iron transport, and iron may facilitate cysteamine-induced duodenal ulceration. We show here that cysteamine-induced ulceration was aggravated by pretreatment of rats with Fe(3+) or Fe(2+) 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 < 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 < 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 < 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
duodenal ulcer  ISOAco1 (Rattus norvegicus)11541091; 11541091protein:increased activity:duodenal mucosa RGD 
duodenal ulcer  IDA 11541091protein:increased activity:duodenal mucosa RGD 
duodenal ulcer  ISOSlc11a2 (Rattus norvegicus)11541091; 11541091mRNA and protein:increased expression:duodenal mucosa RGD 
duodenal ulcer  IEP 11541091mRNA and protein:increased expression:duodenal mucosa RGD 
duodenal ulcer  ISOTfrc (Rattus norvegicus)11541091; 11541091protein:increased expression:duodenal mucosa RGD 
duodenal ulcer  IEP 11541091protein:increased expression:duodenal mucosa RGD 

Objects Annotated

Genes (Rattus norvegicus)
Aco1  (aconitase 1)
Slc11a2  (solute carrier family 11 member 2)
Tfrc  (transferrin receptor)

Genes (Mus musculus)
Aco1  (aconitase 1)
Slc11a2  (solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2)
Tfrc  (transferrin receptor)

Genes (Homo sapiens)
ACO1  (aconitase 1)
SLC11A2  (solute carrier family 11 member 2)
TFRC  (transferrin receptor)


Additional Information