Aluminum in liver cells – the element species matters

Abstract

Aluminum (Al) can be ingested from food and released from packaging and can reach key organs involved in human metabolism, including the liver via systemic distribution. Recent studies discuss the occurrence of chemically distinct Al-species and their interconversion by contact with biological fluids. These Al species can vary with regard to their intestinal uptake, systemic transport, and therefore could have species-specific effects on different organs and tissues. This work aims to assess the in vitro hepatotoxic hazard potential of three different relevant Al species: soluble AlCl₃ and two nanoparticulate Al species were applied, representing for the first time an investigation of metallic nanoparticles besides to mineral bound γ-Al₂O₃ on hepatic cell lines. To investigate the uptake and toxicological properties of the Al species, we used two different human hepatic cell lines: HepG2 and differentiated HepaRG cells. Cellular uptake was determined by different methods including light microscopy, transmission electron microscopy, side-scatter analysis, and elemental analysis. Oxidative stress, mitochondrial dysfunction, cell death mechanisms, and DNA damage were monitored as cellular parameters. While cellular uptake into hepatic cell lines occurred predominantly in the particle form, only ionic AlCl₃ caused cellular effects. Since it is known, that Al species can convert one into another, and mechanisms including ‘trojan-horse’-like uptake can lead to an Al accumulation in the cells. This could result in the slow release of Al ions, for which reason further hazard cannot be excluded. Therefore, individual investigation of the different Al species is necessary to assess the toxicological potential of Al particles.

Keywords:

• Nanoparticles
• aluminum
• toxicology
• liver
• HepG2
• HepaRG
• oxidative stress
• apoptosis

Acknowledgments

We thank the BfR Department of Chemical and Product Safety and the German Institute for Materials Research and Testing for material supply and particle characterization.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This publication, as part of the German-French SolNanoTOX project was funded by the German Research Foundation DFG [Grant Number LA 3411/1-1] and by the French ‘Agence Nationale de la Recherche’ ANR [Project ID ANR-13-IS10-0005] and Deutsche Forschungsgemeinschaft.