title: Amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects.
abstract: BACKGROUND
  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 κB activation, upregulation of key inflammatory factors, and cell death. These effects were observed in a nanoparticle size-dependent and concentration-dependent manner.
  
  
  CONCLUSIONS
  The [NO]/[ONOO(-)] imbalance induced by amorphous silica nanoparticles indicates a potentially deleterious effect of silica nanoparticles on vascular endothelium.
authors: School of Pharmacy and Pharmaceutical Sciences, Faculty of Health Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland.
authors: J Jose
authors: JJ
authors: Corbalan
authors: Carlos
authors: C
authors: Medina
authors: Adam
authors: A
authors: Jacoby
authors: Tadeusz
authors: T
authors: Malinski
authors: Marek W
authors: MW
authors: Radomski
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D020869:Gene Expression Profiling; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000378:metabolism*; D012822:Silicon Dioxide / Q000737:chemistry / Q000633:toxicity*
chemical_list: D015815:Cell Adhesion Molecules; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D012822:Silicon Dioxide; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human