Dietary iron supplementation enhances DSS-induced colitis and associated colorectal carcinoma development in mice
Dietary iron supplementation enhances DSS-induced colitis and associated colorectal carcinoma development in mice
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DOI：
10.1023/a:1015362228659
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发表时间：
2002-06-01
影响因子：
3.1
通讯作者：
Yang, GY
中科院分区：
文献类型：
--
作者：
Seril, DN;Liao, J;Yang, GY
慢性溃疡性结肠炎（UC）患者经常需要补充铁剂来治疗失血引起的贫血。然而，补充铁剂对 UC 相关致癌作用的影响尚不清楚。在这项研究中，评估了富铁饮食对葡聚糖硫酸钠诱导的小鼠急性和慢性结肠炎的影响。在一项短期研究中，与喂食对照饮食的小鼠相比，在饮用液中添加 1% DSS 的小鼠以及铁含量不断增加的 AIN76A 饮食中，急性 UC 的严重程度呈剂量依赖性增加。在补充含不同铁含量的饮食的动物中，观察到结肠上皮表面和发炎区域的铁沉积显着增加，并且 iNOS 和硝基酪氨酸的免疫染色显着增加。在一项长期致癌实验中，与饲喂对照饮食的动物（3/16，19%；P < 0.001）相比，双倍富铁饮食显着增加结直肠肿瘤发病率（14/16，88%）。目前的研究结果对人类 UC 的治疗具有重要意义，并表明膳食铁可以通过增强氧化和亚硝化应激来增强 UC 及其相关的致癌作用。
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.