Phospholipids modifications in human hepatoma cell lines (HepG2) exposed to silver and iron oxide nanoparticles
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NANOTOXICOLOGY
Phospholipids modifications in human hepatoma cell lines (HepG2) exposed to silver and iron oxide nanoparticles Joseph A. Adeyemi1,2 · Carlos Arterio Sorgi1 · Ana Rita Thomazela Machado1 · Abayomi T. Ogunjimi3 · Luiz Gustavo Araujo Gardinassi1 · Viviani Nardini1 · Lucia Helena Faccioli · Lusania Maria Greggi Antunes1 · Fernando Barbosa Jr1 Received: 5 November 2019 / Accepted: 20 May 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Metallic nanoparticles such as silver (Ag NPs) and iron oxide ( Fe3O4 NPs) nanoparticles are high production volume materials due to their applications in various consumer products, and in nanomedicine. However, their inherent toxicities to human cells remain a challenge. The present study was aimed at combining lipidomics data with common phenotypically-based toxicological assays to gain better understanding into cellular response to Ag NPs and Fe3O4 NPs exposure. HepG2 cells were exposed to different concentrations (3.125, 6.25, 12.5, 25, 50 and 100 µg/ml) of the nanoparticles for 24 h, after which they were assayed for toxic effects using toxicological assays like cytotoxicity, mutagenicity, apoptosis and oxidative stress. The cell membrane phospholipid profile of the cells was also performed using shotgun tandem mass spectrometry. The results showed that nanoparticles exposure resulted in concentration-dependent cytotoxicity as well as reduced cytokinesis-block proliferation index (CBPI). Also, there was an increase in the production of ROS and superoxide anions in exposed cells compared to the negative control. The lipidomics data revealed that nanoparticles exposure caused a modulation of the phospholipidome of the cells. A total of 155 lipid species were identified, out of which the fold changes of 23 were significant. The high number of differentially changed phosphatidylcholine species could be an indication that inflammation is one of the major mechanisms of toxicity of the nanoparticles to the cells. Keywords Phospholipids · Phenotypic toxicological assays · Oxidative stress · Mutagenicity · Cell death
Introduction
* Joseph A. Adeyemi [email protected] * Fernando Barbosa Jr [email protected] 1
Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida Do Café S/nº, Ribeirão Preto, São Paulo 14040‑903, Brazil
2
Department of Biology, School of Sciences, Federal University of Technology, P.M.B. 704, Akure, Ondo State, Nigeria
3
Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, 115 S Grand Avenue, Iowa City, Iowa, USA
Advances in nanotechnology and the increasing trend in applications of engineered and manufactured nanomaterials has resulted in a rise in their production over the years (Piccinno et al. 2012; Vance et al. 2015). Giese et al. (2018) predicted a 5% annual growth in the production of frequently used engineered nanomaterials such as silver, cerium o
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