Evidence for regulatory control of iron uptake from ferric maltol across the small intestine of the rat.

1. 59Fe absorption from the novel iron compound, ferric maltol, was studied in rats pretreated twice daily for two weeks with non-radioactive ferric maltol in oral doses containing 7 mg elemental iron. Tissue accumulation of 59Fe 2 h after administration of radioactive ferric maltol into the stomach was significantly lower in iron pretreated animals than in saline-treated controls. 2. 59Fe uptake from ferric maltol into isolated fragments of ileum and of duodenum was of similar magnitude in control animals but in iron-treated animals, duodenal uptake was significantly lower than that of the ileum. 3. Absorption of 59Fe was also investigated in anaesthetized rats after intestinal perfusion with saline (controls) or with 5 mM chenodeoxycholate to render the intestines more permeable. 4. Changes in permeability of the small intestine were monitored by estimating the amount of [14C]-mannitol absorbed and fluid secreted with reference to the non-absorbable [3H]-inulin in the perfusate effluents. 5. Despite the increased permeability of the intestines after bile salt treatment, there was little difference from control in the tissue accumulation of 59Fe from ferric maltol 2 h after intraduodenal administration. However 59Fe absorption from ferrous sulphate was significantly increased after bile salt treatment. 6. Gel filtration profiles of plasma made 5 and 60 min after intraduodenal administration of [59Fe]-ferric [3H]-maltol demonstrated that metal and ligand do not enter the circulation as the complex even when intestinal permeability is increased. 7. Uptake of 59Fe was investigated in isolated fragments of rat small intestine after saline or bile salt perfusion. Although 59Fe uptake from ferric maltol was somewhat greater in the bile salt-treated intestinal fragments, saturable kinetics were still observed. By contrast, "Fe uptake from ferrous sulphate: ascorbate was greatly enhanced by bile salt pretreatment and a very large diffusional component of uptake was evident. 8. It is concluded that iron uptake from ferric maltol may well be under endogenous regulatory control even in damaged intestines, so it is unlikely that this novel iron compound can bring about iron overload when administered orally.