Investigation of a role for reduction in ferric iron uptake by mouse duodenum

59Fe uptake rates by mouse duodenal fragments incubated in vitro were markedly reduced by non-permeable reagents, ferricyanide (oxidising agent) and ferrozine (Fe2+ chelator), in the medium; ferrocyanide had no effect. Reduction of Fe3+, as reflected by an increase in ferrozine-(Fe2+)-chelatable iron, was observed in the presence of the tissue fragments. The generation of Fe2+ occurred linearly with time, was independent of the medium ferrozine concentration, and was not due to release of reducing factors from the duodenal fragments. Fe(3+)-reducing activity was mainly present on the mucosal surface and was localised primarily to the proximal region of the small intestine. Changes in Fe3+ reduction rates closely parallelled the changes in duodenal 59Fe uptake, when metabolic inhibitors or modulators of membrane potential were included in the medium. The enhancement in duodenal mucosal 59Fe uptake in chronic hypoxic and iron-deficient mice parallelled the changes in the tissue reduction of medium Fe3+. Moreover, the rates of reduction were quantitatively similar to rates of uptake. These observations indicate that a sequential reduction and uptake process operates for Fe3+ uptake in mouse duodenum.