Phospholipids modifications in human hepatoma cell lines (HepG2) exposed to silver and iron oxide nanoparticles

• Published in: Archives of toxicology Vol. 94; no. 8; pp. 2625 - 2636
• Main Authors: Adeyemi, Joseph A., Sorgi, Carlos Arterio, Machado, Ana Rita Thomazela, Ogunjimi, Abayomi T., Gardinassi, Luiz Gustavo Araujo, Nardini, Viviani, Faccioli, Lucia Helena, Antunes, Lusania Maria Greggi, Barbosa, Fernando
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2020; Springer Nature B.V
• Subjects: Anions; Apoptosis; Assaying; Biomedical and Life Sciences; Biomedicine; Cell death; Cell lines; Cell membranes; Consumer products; Cytokinesis; Cytotoxicity; Environmental Health; Exposure; Hepatoma; Iron oxides; Lecithin; Lipids; Liver cancer; Mass spectrometry; Mass spectroscopy; Mutagenicity; Nanoparticles; Nanotechnology; Nanotoxicology; Occupational Medicine/Industrial Medicine; Oxidative stress; Pharmacology/Toxicology; Phosphatidylcholine; Phospholipids; Shotguns; Silver; Superoxide; Superoxide anions; Toxicity; Toxicology; Oxidative stress; Phospholipids; Mutagenicity; Cell death; Phenotypic toxicological assays
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-020-02789-0

Metallic nanoparticles such as silver (Ag NPs) and iron oxide (Fe 3 O 4 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 Fe 3 O 4 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.