Mobilisation of recently absorbed ⁵⁹Fe 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.