Journal
ARCHIVES OF TOXICOLOGY
Volume 94, Issue 8, Pages 2625-2636Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00204-020-02789-0
Keywords
Phospholipids; Phenotypic toxicological assays; Oxidative stress; Mutagenicity; Cell death
Categories
Funding
- Sao Paulo Research Foundation (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP) [2015/20725-5, 2018/24069-3]
- Brazilian National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, CNPq) [154866/2018-0]
- Coordenacao de Aperfeicoamento de Pessoal de Ensino Superior-Brasil (CAPES) [001]
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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 mu g/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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