Iron Overload Resulting from the Chronic Oral Administration of Ferric Citrate Impairs Intestinal Immune and Barrier in Mice

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.