Effect of copper, cadmium, mercury, manganese and lead on Fe2+ and Fe3+ absorption in perfused mouse intestine.
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 microM 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+.
Iturri
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Department of Ecological Sciences, Faculty of Sciences, University of Chile, Santiago, Chile.
Nuñez
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D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D005260:Female; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects; D007501:Iron / Q000493:pharmacokinetics*; D007854:Lead / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D008628:Mercury / Q000494:pharmacology; D019216:Metals, Heavy / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010477:Perfusion
D019216:Metals, Heavy; D002104:Cadmium; D007854:Lead; D008345:Manganese; D003300:Copper; D007501:Iron; D008628:Mercury