Phlebotomy increases cadmium uptake in hemochromatosis.
The intestinal absorption of the nephrotoxic environmental pollutant cadmium increases markedly when iron stores are depleted. This may be mediated by an up regulation of the recently identified mucosal transporter DMT1 (Nramp2 or DCT1) for divalent cations. We tested whether the highly increased iron absorption in hereditary hemochromatosis (HH) was accompanied by an enhanced absorption of cadmium and lead. Cadmium and lead in blood and iron status markers were determined in 21 nonsmoking subjects with HH genetically tested for the HFE mutations and in 21 nonsmoking controls matched for age and sex. In subjects with HH on maintenance phlebotomy treatment, blood concentrations of cadmium, but not lead, were significantly higher than in paired controls. There was a strong age-independent positive association between blood cadmium and the number of years of phlebotomy treatment. Blood lead showed a similar but less pronounced consequence of treatment. All HH subjects with lower blood cadmium than the corresponding controls had either no mutation in the HFE gene, were not phlebotomized, or were phlebotomized for only a limited time. Our findings indicate that the treatment rather than the disease increased the cadmium uptake in homozygous HH. Further studies are needed to confirm whether the disease decreased cadmium absorption and whether the absorption was dependent on the genotype.
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Institute of Environmental Medicine, Division of Metals and Health, Karolinska Institutet, Stockholm, Sweden. Agneta.Akesson@imm.ki.se
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D000042:Absorption; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002104:Cadmium / Q000493:pharmacokinetics*; D005260:Female; D005838:Genotype; D006432:Hemochromatosis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007854:Lead / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D018962:Phlebotomy / Q000009:adverse effects*
D002104:Cadmium; D007854:Lead