Counterions determine uptake and effects of aluminum in human intestinal and liver cells. (March 2022)

• Record Type: Journal Article
• Authors: Sieg, Holger; Klusmann, Lisa; Kreß, Lola; Ellermann, Anna Lena; Böhmert, Linda; Thünemann, Andreas F.; Braeuning, Albert
• Is Part Of: Toxicology in vitro. Volume 79(2022)
• Publication Date: 2022-03
• Subjects: Aluminum -- Gastrointestinal uptake -- Counterion -- Acetylacetonate; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2021.105295
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Aluminum (Al) is highly abundant in the biosphere and can occur in different physico-chemical states. It is present in human food and undergoes transitions between dissolved and particulate species during the passage of the gastrointestinal tract. Moreover, in a complex matrix such as food different inorganic and organic counterions can affect the chemical behavior of Al following oral uptake. In this work, the effects of different counterions, namely chloride, citrate, sulfate, lactate and acetylacetonate, on Al uptake and toxicity in the human intestine are studied. The respective Al salts showed different dissolution behavior in biological media and formed nanoscaled particles correlating in reverse with the amount of their dissolved fraction. The passage through the intestinal barrier was studied using a Caco-2 Transwell® system, showing counterion-dependent variance in cellular uptake and transport. In addition, Al toxicity was investigated using Al species (Al 3+, metallic Al 0 and oxidic γAl2 O3 nanoparticles) and counterions individually or in mixtures on Caco-2 and HepG2 cells. The strongest toxicity was observed using a combination of Al species, depending on solubility, and the lipophilic counterion acetylacetonate. Notably, only the combination of both led to toxicity, while both substances individually did not show toxic effects. A toxification of previously non-toxic Al-species by the presence of acetylacetonate is shown here for the first time. The dependency on the concentration of free Al ions was demonstrated using sodium hydrogen phosphate, which was able to counteract the toxic effects by complexing free Al ions. These findings, using Al salts as an example for a common food contaminant, underline the importance of a consideration of the chemical properties of human nutrition, especially dissolution and hydrophobicity, which can significantly influence the cellular uptake and effects of xenobiotic substances. Graphical abstract: Unlabelled Image Highlights: This work investigates aluminum species and counterions in combination on human intestinal and liver cells. The presence of counterions can strongly influence toxic effects in vitro . Cellular uptake and transport of aluminum through the intestinal epithelium is dependent on the applied counterion. A combination of non-toxic substances can lead to cytotoxic effects when applied together.