Dietary iron regulates intestinal cadmium absorption through iron transporters in rats

The intestinal absorption of cadmium (Cd) is influenced by body iron (Fe) status in laboratory animals and humans. In this study we investigated the role of the apical Fe transporter divalent metal transporter 1 (DMT1) and the basolateral Fe exporter metal transporter protein 1 (MTP1) in Cd absorption. Rats were divided into the following groups; an Fe-sufficient (FeS) control group that was fed an FeS diet for 4 weeks (FeS, 4 weeks); an Fe-deficient (FeD) group that was fed an FeD diet for 4 weeks (FeD, 4 weeks); an FeS control group that was fed an FeS diet for 8 weeks (FeS, 8 weeks); an FeD/FeS group that was fed an FeD diet for 4 weeks and then an FeS diet for the following 4 weeks (FeD/FeS, 4 weeks/4 weeks); and an FeD group that was fed an FeD diet for 8 weeks (FeD, 8 weeks). After the 4- and 8-week feeding periods, rats were given a single oral gavage of Cd and were sacrificed 24 h later. The FeD (4 weeks) group developed Fe deficient anemia, but the parameters returned to control levels in the FeD/FeS group (4 weeks/4 weeks). The Cd body burden was greater in FeD (4 weeks) rats compared to FeS control (4 weeks), but returned to control Cd levels in FeD/FeS (4 weeks/4 weeks) rats. In addition, the expression of DMT1 and MTP1 was induced by Fe deficiency in the duodenum of FeD (4 weeks) rats, but was down-regulated to control values in FeD/FeS (4 weeks/4 weeks) rats. The correlation between duodenal DMT1 and MTP1 expression and Cd body burden in rats suggests an important role of DMT1 and MTP1 in Cd absorption.