Mobilisation of recently absorbed Fe in ex vivo perfused rat duodena and the influence of iron status and subsequently absorbed chelators

To investigate the effect of subsequently absorbed metal chelators on recently absorbed ⁵⁹Fe, duodenal segments from iron-deficient and iron-adequate rats were perfused ex vivo until the ⁵⁹Fe tissue load had reached a steady state. Subsequently, the segments were perfused with 3 model chelators and their iron complexes: nitrilotriacetic acid (NTA), ethylenediaminetetraacetic acid (EDTA) and citrate. Of these, NTA and EDTA bind iron much tighter than citrate, and Fe–NTA complexes exchange iron within seconds while Fe-EDTA complexes need 48 h to reach equilibrium.

Duodenal mucosa-to-serosa transport rates were comparable for all 3 chelators and correlated linearly with luminal concentration. Subsequent perfusion with increasing NTA, Fe–NTA(1:2) and EDTA concentrations mobilised increasing amounts of ⁵⁹Fe from the duodenum. Mobilised ⁵⁹Fe moved preferentially back into the luminal perfusate in iron-adequate segments. In iron-deficient segments, ⁵⁹Fe preferentially continued the absorption process across the basolateral membrane. Fe–EDTA(1:1) hardly mobilised any ⁵⁹Fe back into the lumen, though basolateral transfer increased at high concentrations. Citrate and Fe–citrate(1:1) mobilised ⁵⁹Fe only at very high concentrations.

This behaviour is in accordance with the rules of complex chemistry: strong, fast reacting ligands like NTA show most impact. Slowly reacting complexes like Fe–EDTA(1:1) have little mobilising impact in spite of strong affinity between EDTA and iron. The low affinity between iron and citrate can be compensated by large concentration. Moreover, iron-deficient segments show stronger re-uptake of mobilised ⁵⁹Fe from the lumen and a stronger transfer of ⁵⁹Fe from the tissue across the basolateral membrane. Both are compatible with the more marked expression of divalent metal transporter 1 (DMT-1) and IREG-1 at the brushborder and basolateral membrane of iron-deficient enterocytes. The data suggest that iron ions interact with food ligands during their passage from the apical to the basolateral side of duodenal enterocytes.