Hepatic toxicology following single and multiple exposure of engineered nanomaterials utilising a novel primary human 3D
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RESEARCH
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Hepatic toxicology following single and multiple exposure of engineered nanomaterials utilising a novel primary human 3D liver microtissue model Ali Kermanizadeh1,2*, Mille Løhr1, Martin Roursgaard1, Simon Messner3, Patrina Gunness3, Jens M Kelm3, Peter Møller1, Vicki Stone2 and Steffen Loft1
Abstract Background: The liver has a crucial role in metabolic homeostasis as well as being the principal detoxification centre of the body, removing xenobiotics and waste products which could potentially include some nanomaterials (NM). With the ever increasing public and occupational exposure associated with accumulative production of nanomaterials, there is an urgent need to consider the possibility of detrimental health consequences of engineered NM exposure. It has been shown that exposure via inhalation, intratracheal instillation or ingestion can result in NM translocation to the liver. Traditional in vitro or ex vivo hepatic nanotoxicology models are often limiting and/or troublesome (i.e. reduced metabolism enzymes, lacking important cell populations, unstable with very high variability, etc.). Methods: In order to rectify these issues and for the very first time we have utilised a 3D human liver microtissue model to investigate the toxicological effects associated with a single or multiple exposure of a panel of engineered NMs (Ag, ZnO, MWCNT and a positively charged TiO2). Results: Here we demonstrate that the repeated exposure of the NMs is more damaging to the liver tissue as in comparison to a single exposure with the adverse effects more significant following treatment with the Ag and ZnO as compared with the TiO2 and MWCNT NMs (in terms of cytotoxicity, cytokine secretion, lipid peroxidation and genotoxicity). Conclusions: Overall, this study demonstrates that the human microtissue model utilised herein is an excellent candidate for replacement of traditional in vitro single cell hepatic models and further progression of liver nanotoxicology. Keywords: 3D human liver microtissue, Engineered nanomaterials, Inflammation, Lipid peroxidation, Genotoxicity
Background The rapid expansion of technological, scientific and commercial uses of molecular scale materials, their assembly and their unique properties has led to an escalating interest in the fields of nanoscience, nanotechnology and nanomedicine [1]. There are now over 1600 consumer products on the market with a claim of containing aspects of nanotechnology [2]. These applications include medicine, * Correspondence: [email protected] 1 Department of Public Health, University of Copenhagen, Section of Environmental Health, Copenhagen 1014, Denmark 2 Heriot Watt University, School of Life Sciences, Nanosafety research group, Edinburgh EH14 4AS, UK Full list of author information is available at the end of the article
electronics, engineering, cosmetics and textiles [3]. As a negative however, the same unique chemical and physical characteristics which make NMs so desirable might also contribute to their potential adverse effects, which rai
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