Ferric citrate (FC) is an iron-containing phosphate binder used as a food additive for iron supplementation. To explore the potential effect of ferric citrate on intestinal epithelial function, in the present study, we administered the mice orally for 16 weeks with different doses of iron citrate (2.5 mg/day (1.25%), 5 mg/day (2.5%), and 10 mg/day (5.0%)). We found that the iron levels of serum and tissue significantly increased, which caused the body to be in an iron overload state; meanwhile, the villus height, the ratio of villus height to crypt depth, and the number of intraepithelial lymphocytes and goblet cells in jejunum all decreased. Iron overload upregulated the pro-inflammatory cytokines (IL-1β, IL-2, IL-6, TNF-ɑ), while downregulated the anti-inflammatory cytokines (IL-4, IL-10) and sIgA. Moreover, iron overload increased serum d-lactate (D-LA) levels and decreased tight junction proteins (claudin-1, occludin, and ZO-1), MUC-2, and TFF3. In addition, iron overload upregulated the content of MDA and protein carbonyl, while downregulated the activity and content of T-AOC, GSH-PX, SOD, CAT, and GSH. To sum up, the present results showed that long-term oral administration of FC resulted in iron overload, which consequently impaired intestinal immune and barrier function in mice. Meanwhile, the effect on intestinal damage may be highly related to the increase of oxidative stress in the jejunum.

柠檬酸铁（FC）是一种含铁磷酸盐粘合剂，用作补充铁的食品添加剂。为了探讨柠檬酸铁对肠道上皮功能的潜在影响，在本研究中，我们给小鼠口服了16周的不同剂量的柠檬酸铁（2.5 mg /天（1.25％），5 mg /天（2.5％）和10毫克/天（5.0％））。我们发现血清和组织中的铁水平显着增加，从而导致人体处于铁超负荷状态；同时，空肠中的绒毛高度，绒毛高度与隐窝深度的比率以及空肠中上皮内淋巴细胞和杯状细胞的数量均降低。铁过载上调了促炎细胞因子（IL-1β，IL-2，IL-6，TNF-α），而下调了抗炎细胞因子（IL-4，IL-10）和sIgA。而且，铁超负荷会增加血清d-乳酸（D-LA）水平和紧密连接蛋白（claudin-1，occludin和ZO-1），MUC-2和TFF3降低。此外，铁超载上调了MDA和蛋白质羰基的含量，同时下调了T-AOC，GSH-PX，SOD，CAT和GSH的活性和含量。综上所述，目前的结果表明，长期口服FC会导致铁超负荷，从而损害小鼠的肠道免疫和屏障功能。同时，对肠损伤的影响可能与空肠中氧化应激的增加高度相关。