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Metabolomics of silver nanoparticles toxicity in HaCaT cells: structure-activity relationships and role of ionic silver and oxidative stress.
Nanotoxicology. 2016 10; 10(8):1105-17.N

Abstract

The widespread use of silver nanoparticles (AgNPs) is accompanied by a growing concern regarding their potential risks to human health, thus calling for an increased understanding of their biological effects. The aim of this work was to systematically study the extent to which changes in cellular metabolism were dependent on the properties of AgNPs, using NMR metabolomics. Human skin keratinocytes (HaCaT cells) were exposed to citrate-coated AgNPs of 10, 30 or 60 nm diameter and to 30 nm AgNPs coated either with citrate (CIT), polyethylene glycol (PEG) or bovine serum albumin (BSA), to assess the influence of NP size and surface chemistry. Overall, CIT-coated 60 nm and PEG-coated 30 nm AgNPs had the least impact on cell viability and metabolism. The role of ionic silver and reactive oxygen species (ROS)-mediated effects was also studied, in comparison to CIT-coated 30 nm particles. At concentrations causing an equivalent decrease in cell viability, Ag(+)ions produced a change in the metabolic profile that was remarkably similar to that seen for AgNPs, the main difference being the lesser impact on the Krebs cycle and energy metabolism. Finally, this study newly reported that while down-regulated glycolysis and disruption of energy production were common to AgNPs and H2O2, the impact on some metabolic pathways (GSH synthesis, glutaminolysis and the Krebs cycle) was independent of ROS-mediated mechanisms. In conclusion, this study shows the ability of NMR metabolomics to define subtle biochemical changes induced by AgNPs and demonstrates the potential of this approach for rapid, untargeted screening of pre-clinical toxicity of nanomaterials in general.

Authors+Show Affiliations

a CICECO - Aveiro Institute of Materials, Department of Chemistry , University of Aveiro , Aveiro , Portugal .b CESAM & Laboratory of Biotechnology and Cytomics, Department of Biology, University of Aveiro , Aveiro , Portugal , and.a CICECO - Aveiro Institute of Materials, Department of Chemistry , University of Aveiro , Aveiro , Portugal .a CICECO - Aveiro Institute of Materials, Department of Chemistry , University of Aveiro , Aveiro , Portugal .a CICECO - Aveiro Institute of Materials, Department of Chemistry , University of Aveiro , Aveiro , Portugal .a CICECO - Aveiro Institute of Materials, Department of Chemistry , University of Aveiro , Aveiro , Portugal .b CESAM & Laboratory of Biotechnology and Cytomics, Department of Biology, University of Aveiro , Aveiro , Portugal , and.b CESAM & Laboratory of Biotechnology and Cytomics, Department of Biology, University of Aveiro , Aveiro , Portugal , and. c Department of Biology , Faculty of Sciences, University of Porto , Porto , Portugal.a CICECO - Aveiro Institute of Materials, Department of Chemistry , University of Aveiro , Aveiro , Portugal .a CICECO - Aveiro Institute of Materials, Department of Chemistry , University of Aveiro , Aveiro , Portugal .

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27144425

Citation

Carrola, Joana, et al. "Metabolomics of Silver Nanoparticles Toxicity in HaCaT Cells: Structure-activity Relationships and Role of Ionic Silver and Oxidative Stress." Nanotoxicology, vol. 10, no. 8, 2016, pp. 1105-17.
Carrola J, Bastos V, Jarak I, et al. Metabolomics of silver nanoparticles toxicity in HaCaT cells: structure-activity relationships and role of ionic silver and oxidative stress. Nanotoxicology. 2016;10(8):1105-17.
Carrola, J., Bastos, V., Jarak, I., Oliveira-Silva, R., Malheiro, E., Daniel-da-Silva, A. L., Oliveira, H., Santos, C., Gil, A. M., & Duarte, I. F. (2016). Metabolomics of silver nanoparticles toxicity in HaCaT cells: structure-activity relationships and role of ionic silver and oxidative stress. Nanotoxicology, 10(8), 1105-17. https://doi.org/10.1080/17435390.2016.1177744
Carrola J, et al. Metabolomics of Silver Nanoparticles Toxicity in HaCaT Cells: Structure-activity Relationships and Role of Ionic Silver and Oxidative Stress. Nanotoxicology. 2016;10(8):1105-17. PubMed PMID: 27144425.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metabolomics of silver nanoparticles toxicity in HaCaT cells: structure-activity relationships and role of ionic silver and oxidative stress. AU - Carrola,Joana, AU - Bastos,Verónica, AU - Jarak,Ivana, AU - Oliveira-Silva,Rui, AU - Malheiro,Eliana, AU - Daniel-da-Silva,Ana L, AU - Oliveira,Helena, AU - Santos,Conceição, AU - Gil,Ana M, AU - Duarte,Iola F, Y1 - 2016/05/04/ PY - 2016/5/5/entrez PY - 2016/5/5/pubmed PY - 2017/6/24/medline KW - AgNPs KW - NMR spectroscopy KW - keratinocytes KW - metabolism KW - reactive oxygen species SP - 1105 EP - 17 JF - Nanotoxicology JO - Nanotoxicology VL - 10 IS - 8 N2 - The widespread use of silver nanoparticles (AgNPs) is accompanied by a growing concern regarding their potential risks to human health, thus calling for an increased understanding of their biological effects. The aim of this work was to systematically study the extent to which changes in cellular metabolism were dependent on the properties of AgNPs, using NMR metabolomics. Human skin keratinocytes (HaCaT cells) were exposed to citrate-coated AgNPs of 10, 30 or 60 nm diameter and to 30 nm AgNPs coated either with citrate (CIT), polyethylene glycol (PEG) or bovine serum albumin (BSA), to assess the influence of NP size and surface chemistry. Overall, CIT-coated 60 nm and PEG-coated 30 nm AgNPs had the least impact on cell viability and metabolism. The role of ionic silver and reactive oxygen species (ROS)-mediated effects was also studied, in comparison to CIT-coated 30 nm particles. At concentrations causing an equivalent decrease in cell viability, Ag(+)ions produced a change in the metabolic profile that was remarkably similar to that seen for AgNPs, the main difference being the lesser impact on the Krebs cycle and energy metabolism. Finally, this study newly reported that while down-regulated glycolysis and disruption of energy production were common to AgNPs and H2O2, the impact on some metabolic pathways (GSH synthesis, glutaminolysis and the Krebs cycle) was independent of ROS-mediated mechanisms. In conclusion, this study shows the ability of NMR metabolomics to define subtle biochemical changes induced by AgNPs and demonstrates the potential of this approach for rapid, untargeted screening of pre-clinical toxicity of nanomaterials in general. SN - 1743-5404 UR - https://www.unboundmedicine.com/medline/citation/27144425/Metabolomics_of_silver_nanoparticles_toxicity_in_HaCaT_cells:_structure_activity_relationships_and_role_of_ionic_silver_and_oxidative_stress_ L2 - https://www.tandfonline.com/doi/full/10.1080/17435390.2016.1177744 DB - PRIME DP - Unbound Medicine ER -