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Cited by 59Aluminum toxicity and tolerance in plants and animalsHeavy Metal Exposure and ToxicityDrug Solubulity and Delivery Systems

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The Chemical Species of Aluminum Influences Its Paracellular Flux across and Uptake into Caco-2 Cells, a Model of Gastrointestinal Absorption

Zhou, Yuzhao, Yokel, Robert A.·2005·Toxicological Sciences
DOI 10.1093/toxsci/kfi216
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Abstract

Aluminum (Al) can cause neurotoxicity, a low-turnover osteomalacia, and microcytic anemia. To test the null hypothesis that the chemical form (species) of Al does not influence its mechanism or rate of absorption from the gastrointestinal tract, Al flux across and uptake into Caco-2 cells was investigated. Caco-2 cells were grown on porous membranes mounted in vertical diffusion chambers or in 35-mm-diameter plastic cell culture dishes. When 8 mM 27Al was introduced as the ion, citrate, maltolate, fluoride, or hydroxide, the apical to basolateral apparent permeability (Papp) of Al correlated highly with the Papp of lucifer yellow (LY), a paracellular marker, except when introduced as Al hydroxide. The uptake rate of Al when introduced as the fluoride was > when introduced as the ion > maltolate > citrate > hydroxide. The activation energy of Al introduced as the ion, citrate, maltolate, and fluoride, determined from Arrhenius plots, was 13-22 KJ/mol, suggesting diffusion-mediated uptake. With exposure to 2 microM Al (containing 26Al as a tracer) introduced as the ion, hydroxide, citrate, and fluoride, Al and LY Papp were consistent with results obtained with 8 mM Al, but were not Al species dependent. Approximately 0.015% of the 26Al fluxed across the cell monolayer; 0.75% was associated with cells. Lumogallion staining imaged by confocal laser microscopy showed Al co-localized with DAPI in the nucleus. The results suggest that (1) soluble Al species predominantly diffuse through the paracellular pathway, (2) the ligand-dependent flux rate of Al is due to an effect on the tight junctions, (3) Caco-2 cell uptake of Al is a diffusion process, and (4) the ligand can influence the rate of cellular Al uptake.

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  • Many antacids contain 104-208 mg of aluminium per tablet, capsule or 5 ml of suspension.

    “Many antacids contain 104–208 mg of Al per tablet, capsule or 5 ml of suspension (Zhou and Yokel, 2005).”

    From Aluminium toxicosis: a review of toxic actions and effects (2019) · cites this paper as Zhou and Yokel, 2005

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Metadata

Authors
Zhou, Y., & Yokel, R. A.
Affiliations
University of Kentucky (US)
Corresponding author
Zhou, Yuzhao
ORCID
Yokel, Robert A.
Venue
Toxicological Sciences
Publisher
Oxford University Press (OUP)
Published
2005-06-02
Volume
87
Issue
1
Pages
15-26
ISSN
  • 1096-0929 (ISSN-L)
  • 1096-6080
DOI
10.1093/toxsci/kfi216
OpenAlex
W2005392040
Cited by
59
References
1
Citations by year
2025: 2 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 1 · 2019: 5 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 4 · 2014: 6 · 2013: 2 · 2012: 6
FWCI
2.41
Type
journal article
Language
en
Open access
closed
Locations
  • Toxicological Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • UKnowledge (University of Kentucky) (submittedVersion)
Funders
  • U.S. Environmental Protection Agency
  • University of Missouri
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Aluminum toxicity and tolerance in plants and animals
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
Keywords
aluminum, aluminum species, gastrointestinal absorption, paracellular pathway, Caco-2 cells, aluminum uptake, citrate, fluoride, aluminum hydroxide, tight junctions, diffusion, aluminum neurotoxicity
MeSH terms
Aluminum, Humans, Intestinal Absorption, Microscopy, Confocal, Caco-2 Cells

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