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 100 μmol/L; Pb: 1 μmol/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.
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 100 μmol/L; Pb: 1 μmol/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.
Authors: Farzana Kastury; Euan Smith; Enzo Lombi; Martin W Donnelley; Patricia L Cmielewski; David W Parsons; Matt Noerpel; Kirk G Scheckel; Andrew M Kingston; Glenn R Myers; David Paterson; Martin D de Jonge; Albert L Juhasz Journal: Environ Sci Technol Date: 2019-09-11 Impact factor: 9.028
Authors: Farzana Kastury; Silvia Placitu; John Boland; Ranju R Karna; Kirk G Scheckel; Euan Smith; Albert L Juhasz Journal: Environ Int Date: 2019-07-05 Impact factor: 9.621
Authors: Karen D Bradham; Gary L Diamond; Clay M Nelson; Matt Noerpel; Kirk G Scheckel; Brittany Elek; Rufus L Chaney; Qing Ma; David J Thomas Journal: Environ Sci Technol Date: 2018-11-14 Impact factor: 9.028
Authors: Jennifer L Griggs; David J Thomas; Rebecca Fry; Karen D Bradham Journal: J Toxicol Environ Health B Crit Rev Date: 2021-06-06 Impact factor: 8.071