Body iron homeostasis is maintained by the regulation of iron absorption in the first portion of the small intestine. Previous studies have shown that some trace metal cations may have an inhibitory effect on inorganic iron absorption. In view of the possible nutritional and toxicological implications of this inhibition, we decided to study the effect of Cu²⁺, Cd²⁺, Hg²⁺, Pb²⁺, and Mn²⁺ on Fe²⁺ and Fe³⁺ intestinal uptake. To that end, the duodenal portion of the mouse intestine was perfused with 1 µM ⁵⁵Fe either in the 2+ or 3+ redox state, in the absence or presence of a 10-fold molar excess of Cd²⁺, Cu²⁺, Hg²⁺, Mn²⁺, or Pb²⁺. It was found that Cd²⁺ and Cu²⁺, but not Hg²⁺, Mn²⁺, or Pb²⁺, significantly inhibited the uptake of Fe²⁺ (p < 0.001). Surprisingly, the observed inhibition by Cu²⁺ and Cd²⁺ was dependent on the iron redox state, since neither cation inhibited Fe³⁺ uptake by mouse duodenum. Similarly, no inhibition of Fe³⁺ uptake was observed with a 10-fold molar excess of Hg²⁺, Mn²⁺, or Pb²⁺. These results indicate that inhibition of iron uptake by Cu²⁺ and Cd²⁺ takes place only in a reducing environment. Therefore, under the common oxidative conditions found in nutrients no inhibition of non-heme Fe uptake by Cu²⁺ and Cd²⁺, as well as Mn²⁺, Hg²⁺ and Pb²⁺ is to be expected. We propose either that Fe²⁺ and Fe³⁺ are transported through two different mechanisms, or that the enterocyte-mediated reduction of Fe³⁺, and the ensuing transport of Fe²⁺ are processes coupled in such a way that they are refractory to inhibition by Cu²⁺ and Cd²⁺.

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