Grantee Research Project Results
2004 Progress Report: Intestinal Aluminum Absorption and Bioavailability from Representative Aluminum Species
EPA Grant Number: R829783Title: Intestinal Aluminum Absorption and Bioavailability from Representative Aluminum Species
Investigators: Yokel, Robert A. , McNamara, Patrick J.
Institution: University of Kentucky
EPA Project Officer: Page, Angela
Project Period: July 1, 2002 through June 30, 2005 (Extended to June 30, 2006)
Project Period Covered by this Report: July 1, 2004 through June 30, 2005
Project Amount: $515,720
RFA: Health Effects of Chemical Contaminants in Drinking Water (2001) RFA Text | Recipients Lists
Research Category: Drinking Water , Human Health , Water
Objective:
The objective of this research project is to determine the conditions and routes of intestinal absorption of aluminum (Al) when introduced as a number of different chemical species.
Progress Summary:
The application submitted to the U.S. Environmental Protection Agency proposed two major projects. The first involved the use of Caco-2 cells as an in vitro model of the gastrointestinal tract. It was proposed to compare the flux of Al as ion, citrate, maltolate, hydroxide, and fluoride species across a monolayer of Caco-2 cells, as well as their uptake by these cells. When introduced as 8 mM 27Al, the results suggested that these five chemical species fluxed across Caco-2 cells through the paracellular pathway. Therefore, the chemical species of Al should not impact on its site and mechanism of absorption. Results of uptake studies of Al by the Caco-2 cells showed considerably greater uptake when introduced as the ion or fluoride, for which uptake was concentrative, than the citrate, maltolate, or hydroxide. The mechanism of uptake appears to be diffusion. The temperature dependence of Al uptake as the ion, citrate, fluoride, and maltolate was determined to gain insight into the mechanism of Al uptake into Caco-2 cells. The energy of activation of Al uptake, calculated from the Årrhenius plot for these four Al species, was low and not significantly different.
The results are generally below the range associated with active, energy-dependent transport, suggesting Al enters Caco-2 cells through a channel rather than by carrier-mediated transport. Using lumogallion, which forms a fluorescent complex with Al, and the nuclear marker DAPI, confocal microscopy showed Al distribution into Caco-2 cells, particularly into the nucleus. Al distribution did not appear to be different in cells that were not exposed to added Al and those exposed to Al as the ion, citrate, maltolate, hydroxide, or fluoride. A limited study was conducted to concurrently determine Al uptake into and across Caco-2 cells when the Al was introduced as 2 μM 26Al.
The results showed no significant difference in the uptake into or flux across the cells when the Al was introduced as the Al ion, citrate, maltolate, or fluoride. About 50-fold more 26Al was taken up into the cells than fluxed across the Caco-2 cells. Overall, these results suggest that at low concentrations of Al, which model the Al concentration in drinking water, the soluble Al species would be similarly absorbed. At much higher Al concentrations, however, which model the use of Al antacid/phosphate binders, the presence of ligands that complex Al, such as fluoride, citrate, and maltolate, can have a significant effect on Al bioavailability.
The second study was designed to determine the bioavailability of Al in Fisher 344 rats, using 26Al as a tracer and accelerator mass spectrometric analysis. Al, approximately 65 µM, was given as the ion, citrate, maltolate, and fluoride. The oral bioavailability of Al citrate was greater than Al maltolate, which was greater than Al fluoride, which in turn was greater than Al ion. These differences were not statistically significant. The maximum concentration (Cmax) and time to Cmax (Tmax) were not significantly different among these four Al species. Tmax averaged 1.2 hours. The results suggest that at this Al concentration, which is above that typical of drinking water and below that achieved with the use of Al antacid/phosphate binders, the presence of citrate, maltolate, and fluoride do not greatly influence Al bioavailability.
Future Activities:
We will complete the analysis of results of the determination of the oral bioavailability of Al as the ion, citrate, maltolate, and fluoride in the Fisher 344 rat using 26Al as a tracer for Al. We will compare the time-course of Al absorption to its associated ligand when Al citrate and maltolate are administered by 14C determination from [ 14C]-citrate and [ 14C]-maltolate.
Journal Articles on this Report : 1 Displayed | Download in RIS Format
| Other project views: | All 8 publications | 2 publications in selected types | All 2 journal articles |
|---|
| Type | Citation | ||
|---|---|---|---|
|
|
Zhou Y, Yokel RA. The chemical species of aluminum influences its paracellular flux across and uptake into Caco-2 cells, a model of gastrointestinal absorption. Toxicological Sciences 2005;87(1):15-26. |
R829783 (2004) R829783 (Final) |
Exit Exit |
Supplemental Keywords:
accelerator mass spectroscopy, Caco-2 cells, decisionmaking, drinking water, metal absorption, rat, aluminum, Al, ion, citrate, maltolate, hydroxide, fluoride, temperature dependence, Al uptake, ligands,, RFA, Health, Scientific Discipline, Water, Waste, Risk Assessments, Environmental Chemistry, Contaminated Sediments, Environmental Microbiology, Hydrology, Drinking Water, other - exposure, aluminum, aluminum toxicokinetics, treatment, contaminated sediment, ecological risk assessment, water quality, water quality parameters, human exposure, metal absorption, chemical contaminants, groundwater disinfection, neurotoxicity, monitoring, exposure, drinking water contaminants, drinking water treatment, apoptosis, water treatment, human health effects, human health risk, aquifer characteristics, drinking water distribution systemRelevant Websites:
http://www.mc.uky.edu/Pharmacy/faculty/robertyokel.html Exit
http://www.mc.uky.edu/Pharmacy/faculty/patrickmcnamara.html Exit
Progress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.