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Dietary Iron Supplementation Enhances DSS-Induced Colitis and Associated Colorectal Carcinoma Development in Mice
Abstract
Chronic ulcerative colitis (UC) patients frequently require iron supplementation to remedy anemia due to blood loss. However, the effect of iron supplementation on UC-associated carcinogenesis is unknown. In this study, the effect of an iron-enriched diet on dextran sulfate sodium-induced acute and chronic colitis in mice was assessed. In a short-term study, mice administered 1% DSS in the drinking fluid and an AIN76A diet containing increasing levels of iron exhibited dose-dependent increases in the severity of acute UC as compared to mice fed a control diet. A marked increase in iron deposition on the epithelial surface of the colon and in the inflamed areas and immunostaining for iNOS and nitrotyrosine were observed in the animals supplemented with diets containing different levels of iron. In a long-term carcinogenesis experiment, a twofold iron-enriched diet significantly increased colorectal tumor incidence (14/16, 88%) as compared with animals fed the control diet (3/16, 19%; P < 0.001). The present findings have implications for the management of human UC and suggest that dietary iron can enhance UC and its associated carcinogenesis by augmenting oxidative and nitrosative stress.
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“In animal models, iron-induced increase in oxidative damage was associated with gastric inflammation, induction of gastric ulcers and increase in colorectal cancer (Seril et al., 2002;Naito et al., 1995).”
From Iron, Oxidative Stress and Health (2012) · cites this paper as Seril et al., 2002
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Metadata
- Authors
- Seril, D. N., Liao, J., Ho, K.-L. K., Warsi, A., Yang, C. S., & Yang, G.-Y.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- Venue
- Digestive Diseases and Sciences
- Published
- 2002-06
- Volume
- 47
- Issue
- 6
- Pages
- 1266-1278
- ISSN
- 0163-2116 (ISSN-L)
- 1573-2568
- OpenAlex
- W1591222484
- Cited by
- 183
- References
- 37
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 9 · 2021: 11 · 2020: 10 · 2019: 9 · 2018: 6 · 2017: 7 · 2016: 7 · 2015: 4 · 2014: 14 · 2013: 11 · 2012: 9
- FWCI
- 4.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Digestive Diseases and Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Environmental Health Sciences (ES0052)
- Topics
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
- Keywords
- dietary iron supplementation, ulcerative colitis, DSS-induced colitis, colorectal carcinogenesis, nitrosative stress, oxidative stress, inducible nitric oxide synthase, nitrotyrosine, AIN-76A diet
- MeSH terms
- Animals, Colitis, Ulcerative, Colon, Disease Models, Animal, Dose-Response Relationship, Drug, Female, Mice, Inbred C57BL, Colorectal Neoplasms, Dextran Sulfate, Oxidative Stress, Disease Progression, Iron, Dietary, Dietary Supplements, Mice
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