Effects of copper nanoparticles on rat cerebral microvessel endothelial cells

Nanomedicine (Lond). 2012 Jun;7(6):835-46. doi: 10.2217/nnm.11.154. Epub 2012 Feb 16.

Abstract

Aim: The purpose of the current study was to determine whether copper nanoparticles (Cu-NPs) can induce the release of proinflammatory mediators that influence the restrictive characteristics of the blood-brain barrier.

Material & methods: Confluent rat brain microvessel endothelial cells (rBMECs) were treated with well-characterized Cu-NPs (40 or 60 nm). Cytotoxicity of the Cu-NPs was evaluated by cell proliferation assay (1.5-50 µg/ml). The extracellular concentrations of proinflammatory mediators (IL-1β, IL-2, TNF-α and prostaglandin E(2)) were evaluated by ELISA.

Results: The exposure of Cu-NPs at low concentrations increases cellular proliferation of rBMECs, by contrast, high concentrations induce toxicity. Prostaglandin E(2) release was significantly increased (threefold; 8 h) for Cu-NPs (40 and 60 nm). The extracellular levels of both TNF-α and IL-1β were significantly elevated following exposure to Cu-NPs. The P-apparent ratio, as an indicator of increased permeability of rBMEC was approximately twofold for Cu-NPs (40 and 60 nm).

Conclusion: These data suggest that Cu-NPs can induce rBMEC, proliferation at low concentrations and/or induce blood-brain barrier toxicity and potential neurotoxicity at high concentrations.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood-Brain Barrier / cytology
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / immunology*
  • Cell Membrane Permeability / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Copper / chemistry
  • Copper / immunology*
  • Copper / toxicity
  • Dinoprostone / immunology
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / immunology
  • Interleukin-1beta / immunology
  • Interleukin-2 / immunology
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • Nanoparticles / ultrastructure
  • Peptide Fragments / immunology
  • Rats
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Interleukin-1beta
  • Interleukin-2
  • Peptide Fragments
  • Tumor Necrosis Factor-alpha
  • interleukin-1beta (163-171)
  • Copper
  • Dinoprostone