Impact of iron oxide nanoparticles on xenobiotic metabolism in HepaRG cells
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NANOTOXICOLOGY
Impact of iron oxide nanoparticles on xenobiotic metabolism in HepaRG cells Linn Voss1 · Kiymet Yilmaz1 · Lea Burkard1 · Janja Vidmar2 · Valerie Stock1 · Ute Hoffmann3 · Oliver Pötz4 · Helen Sophie Hammer4 · Matthias Peiser1 · Albert Braeuning1 · Katrin Löschner2 · Linda Böhmert1 · Holger Sieg1 Received: 22 July 2020 / Accepted: 2 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Iron oxide nanoparticles are used in various industrial fields, as a tool in biomedicine as well as in food colorants, and can therefore reach human metabolism via oral uptake or injection. However, their effects on the human body, especially the liver as one of the first target organs is still under elucidation. Here, we studied the influence of different representative iron oxide materials on xenobiotic metabolism of HepaRG cells. These included four iron oxide nanoparticles, one commercially available yellow food pigment (E172), and non-particulate ionic control F eSO4. The nanoparticles had different chemical and crystalline structures and differed in size and shape and were used at a concentration of 50 µg Fe/mL. We found that various CYP enzymes were downregulated by some but not all iron oxide nanoparticles, with the F e3O4-particle, both γ-Fe2O3-particles, and FeSO4 exhibiting the strongest effects, the yellow food pigment E172 showing a minor effect and an α-Fe2O3 nanoparticle leading to almost no inhibition of phase I machinery. The downregulation was seen at the mRNA, protein expression, and activity levels. Thereby, no dependency on the size or chemical structure was found. This underlines the difficulty of the grouping of nanomaterials regarding their physiological impact, suggesting that every iron oxide nanoparticle species needs to be evaluated in a case-by-case approach. Keywords Nanotechnology · Iron oxide nanoparticles · Xenobiotic metabolism · Liver · Toxicity
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00204-020-02904-1) contains supplementary material, which is available to authorized users. * Linda Böhmert [email protected] * Holger Sieg [email protected] 1
German Federal Institute for Risk Assessment (BfR), Max‑Dohrn‑Straße 8‑10, 10589 Berlin, Germany
2
National Food Institute, Technical University of Denmark, Kemitorvet, Building 201, 2800 Kgs Lyngby, Denmark
3
Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of Tübingen, Auerbachstr. 112, 70376 Stuttgart, Germany
4
SIGNATOPE GmbH, Markwiesenstraße 55, 72770 Reutlingen, Germany
Iron oxide nanoparticles (ION) are applied in various industries, due to their unique physicochemical properties. For example, they are used as contrast agents and to facilitate drug delivery in the medical sector (McAteer et al. 2010; Rosen et al. 2012; Vangijzegem et al. 2019). Moreover, iron oxides are approved food pigments and are shown to contain significant amounts of nanoparticles (Voss et al.
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