Does lead use the intestinal absorptive pathways of iron? Impact of iron status on murine ²¹⁰Pb and ⁵⁹Fe absorption in duodenum and ileum in vivo

Background: Human isotope studies and epidemiological trials are controversial as to whether lead absorption shares the absorptive pathways of iron and whether body lead content can be reduced by iron supplementation. Aim: To compare the impact of iron-deficiency on ⁵⁹Fe- and ²¹⁰Pb-absorption rates in duodenal and ileal segments. Methods: ⁵⁹Fe- and ²¹⁰Pb-absorption was determined in ligated duodenal and ileal segments from juvenile and adult iron-deficient and iron-adequate C57Bl6 wild-type mice (n=6) in vivo at luminal concentrations corresponding to human exposure (Fe: 1 and 100μmol/L; Pb: 1μmol/L). Results and discussion: ⁵⁹Fe-absorption increased 10-15-fold in iron-deficient duodena from adult and adolescent mice. Ileal ⁵⁹Fe-absorption was 4-6 times lower than in iron-adequate duodena showing no adaptation to iron-deficiency. This in accordance to expectation as the divalent metal transport 1 (DMT1) shows low ileal expression levels. Juvenile ⁵⁹Fe-absorption was about twice as high as in adult mice. In contrast, duodenal ²¹⁰Pb-absorption was increased only 1.5-1.8-fold in iron-deficiency in juvenile and adult mice and, again in contrast to ⁵⁹Fe, ileal ²¹⁰Pb-absorption was as high as in iron-adequate duodena. Conclusions: The findings suggest a DMT1-independent pathway to mediate lead absorption along the entire small intestine in addition to DMT1-mediated duodenal uptake. Ileal lead absorption appears substantial, due the much longer residence of ingesta in the distal small intestine. Differences in lead-solubility and -binding to luminal ligands can, thus, explain the conflicting findings regarding the impact of iron-status on lead absorption. They need to be considered in future studies.