Effects of various Fe compounds on the bioavailability of Pb contained in orally ingested soils in mice: Mechanistic insights and health implications

Reducing lead (Pb) exposure via oral ingestion of contaminated soils is highly relevant for child health. Elevating dietary micronutrient iron (Fe) intake can reduce Pb oral bioavailability while being beneficial for child nutri-tional health. However, the practical performance of various Fe compounds was not assessed. Here, based on mouse bioassays, ten Fe compounds applied to diets (100-800 mg Fe kg-1) reduced Pb oral relative bioavail-ability (RBA) in two soils variedly depending on Fe forms. EDTA-FeNa was most efficient, which reduced Pb-RBA in a soil from 79.5 +/- 14.7 % to 23.1 +/- 2.72 % (71 % lower) at 100 mg Fe kg -1 in diet, more effective than other 9 compounds at equivalent or higher doses (3.6-68 % lower). When EDTA-FeNa, ferrous gluconate, ferric citrate, and ferrous bisglycinate were supplemented, Fe-Pb co-precipitation was not observed in the intestinal tract. EDTA-FeNa, ferrous gluconate, ferric citrate, and ferrous sulfate suppressed duodenal divalent metal transporter 1 (DMT1)mRNA relative expression similarly (27-68 % lower). In comparison, among ten compounds, EDTA-FeNa elevated Fe concentrations in mouse liver, kidney, and blood (1.50-2.69-fold higher) most efficiently, suggesting the most efficient Fe absorption that competed with Pb. In addition, EDTA was unique from other organic ligands, ingestion of which caused 12.0-fold higher Pb urinary excretion, decreasing Pb concentrations in mouse liver, kidney, and blood by 68-88 %. The two processes (Fe-Pb absorption competition and Pb urinary excretion with EDTA) interacted synergistically, leading to the lowest Pb absorption with EDTA-FeNa. The results provide evidence of a better inhibition of Pb absorption by EDTA-FeNa, highlighting that EDTA-FeNa may be the most appropriate supplement for intervention on human Pb exposure. Future researches are needed to assess the effectiveness of EDTA-FeNa for intervention on human Pb exposure.

Automated summary

Reducing lead exposure through oral ingestion of contaminated soils can be achieved by increasing dietary iron intake, with EDTA-FeNa being the most efficient iron compound. The study demonstrates that EDTA-FeNa reduces lead bioavailability and promotes lead excretion through urine. These findings highlight the potential of EDTA-FeNa as an effective intervention for lead exposure.