Skip Navigation



ToxSci Advance Access published online on June 2, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi216
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
87/1/15    most recent
kfi216v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Zhou, Y.
Right arrow Articles by Yokel, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhou, Y.
Right arrow Articles by Yokel, R. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received January 25, 2005
Accepted May 31, 2005

Biotransformation and Toxicokinetics

The chemical species of aluminum influences its paracellular flux across and uptake into Caco-2 cells, a model of gastrointestinal absorption

Yuzhao Zhou 1 and Robert A. Yokel 2*

1 Graduate Center for Toxicology, University of Kentucky Medical Center, Lexington, KY, 40536-0305
2 Graduate Center for Toxicology, University of Kentucky Medical Center, Lexington, KY, 40536-0305; College of Pharmacy, University of Kentucky Medical Center, Lexington, KY, 40536-0082

* To whom correspondence should be addressed.
Robert A. Yokel, E-mail: ryokel{at}email.uky.edu


  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 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 Årrhenius plots, was 13-22 KJ/mol, suggesting diffusion-mediated uptake. With exposure to 2 µM 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 colocalized with DAPI in the nucleus. The results suggest 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.

Keywords: Aluminum absorption; Caco-2 cells; chemical species; flux; paracellular pathway and uptake.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.