Amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects

J Jose Corbalan1,2, Carlos Medina1, Adam Jacoby2, Tadeusz Malinski2, Marek W Radomski11School of Pharmacy and Pharmaceutical Sciences, Faculty of Health Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland; 2Department of Chemistry and Biochemistry, Ohio University, Athens, OH, USABack...

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Autores principales:	Corbalan JJ, Medina C, Jacoby A, Malinski T, Radomski MW
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/cd1b700b19b44ff69074bd5e6737cb67
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spelling	oai:doaj.org-article:cd1b700b19b44ff69074bd5e6737cb672021-12-02T03:54:01ZAmorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects1176-91141178-2013https://doaj.org/article/cd1b700b19b44ff69074bd5e6737cb672011-11-01T00:00:00Zhttp://www.dovepress.com/amorphous-silica-nanoparticles-trigger-nitric-oxideperoxynitrite-imbal-a8629https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013J Jose Corbalan1,2, Carlos Medina1, Adam Jacoby2, Tadeusz Malinski2, Marek W Radomski11School of Pharmacy and Pharmaceutical Sciences, Faculty of Health Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland; 2Department of Chemistry and Biochemistry, Ohio University, Athens, OH, USABackground: The purpose of this study was to investigate the mechanism of noxious effects of amorphous silica nanoparticles on human endothelial cells.Methods: Nanoparticle uptake was examined by transmission electron microscopy. Electrochemical nanosensors were used to measure the nitric oxide (NO) and peroxynitrite (ONOO-) released by a single cell upon nanoparticle stimulation. The downstream inflammatory effects were measured by an enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, and flow cytometry, and cytotoxicity was measured by lactate dehydrogenase assay.Results: We found that the silica nanoparticles penetrated the plasma membrane and rapidly stimulated release of cytoprotective NO and, to a greater extent, production of cytotoxic ONOO-. The low [NO]/[ONOO-] ratio indicated increased nitroxidative/oxidative stress and correlated closely with endothelial inflammation and necrosis. This imbalance was associated with nuclear factor &kappa;B activation, upregulation of key inflammatory factors, and cell death. These effects were observed in a nanoparticle size-dependent and concentration-dependent manner.Conclusion: The [NO]/[ONOO-] imbalance induced by amorphous silica nanoparticles indicates a potentially deleterious effect of silica nanoparticles on vascular endothelium.Keywords: amorphous silica nanoparticles, nanotoxicology, nitric oxide, peroxynitrite, inflammation, risk factorsCorbalan JJMedina CJacoby AMalinski TRadomski MWDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 2821-2835 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Corbalan JJ Medina C Jacoby A Malinski T Radomski MW Amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects
description	J Jose Corbalan1,2, Carlos Medina1, Adam Jacoby2, Tadeusz Malinski2, Marek W Radomski11School of Pharmacy and Pharmaceutical Sciences, Faculty of Health Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland; 2Department of Chemistry and Biochemistry, Ohio University, Athens, OH, USABackground: The purpose of this study was to investigate the mechanism of noxious effects of amorphous silica nanoparticles on human endothelial cells.Methods: Nanoparticle uptake was examined by transmission electron microscopy. Electrochemical nanosensors were used to measure the nitric oxide (NO) and peroxynitrite (ONOO-) released by a single cell upon nanoparticle stimulation. The downstream inflammatory effects were measured by an enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, and flow cytometry, and cytotoxicity was measured by lactate dehydrogenase assay.Results: We found that the silica nanoparticles penetrated the plasma membrane and rapidly stimulated release of cytoprotective NO and, to a greater extent, production of cytotoxic ONOO-. The low [NO]/[ONOO-] ratio indicated increased nitroxidative/oxidative stress and correlated closely with endothelial inflammation and necrosis. This imbalance was associated with nuclear factor &kappa;B activation, upregulation of key inflammatory factors, and cell death. These effects were observed in a nanoparticle size-dependent and concentration-dependent manner.Conclusion: The [NO]/[ONOO-] imbalance induced by amorphous silica nanoparticles indicates a potentially deleterious effect of silica nanoparticles on vascular endothelium.Keywords: amorphous silica nanoparticles, nanotoxicology, nitric oxide, peroxynitrite, inflammation, risk factors
format	article
author	Corbalan JJ Medina C Jacoby A Malinski T Radomski MW
author_facet	Corbalan JJ Medina C Jacoby A Malinski T Radomski MW
author_sort	Corbalan JJ
title	Amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects
title_short	Amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects
title_full	Amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects
title_fullStr	Amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects
title_full_unstemmed	Amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects
title_sort	amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/cd1b700b19b44ff69074bd5e6737cb67
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Amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects

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