Effects of copper nanoparticles on rat cerebral microvessel endothelial cells

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 E2) 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 E2 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. Original submitted 9 June 2011; Revised submitted 1 August 2011; Published online 16 February 2012