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

  • Nanotoxicology
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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.

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Acknowledgements

This research was supported by São Paulo Research Foundation (Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP, Processos 2015/20725-5 and 2018/24069-3), the Brazilian National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq), Processo 154866/2018-0 and the Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior—Brasil (CAPES)—Finance Code 001.

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Adeyemi, J.A., Sorgi, C.A., Machado, A.R.T. et al. Phospholipids modifications in human hepatoma cell lines (HepG2) exposed to silver and iron oxide nanoparticles. Arch Toxicol 94, 2625–2636 (2020). https://doi.org/10.1007/s00204-020-02789-0

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