Recovery of redox homeostasis altered by CuNPs in H4IIE liver cells does not reduce the cytotoxic effects of these NPs An investigation using aryl hydrocarbon receptor (AhR) dependent antioxidant activity

The generation of reactive oxygen species (ROS) and consequent oxidative stress is regarded as a relevant mechanism for nanoparticle toxicity. In cells, the activation of the aryl hydrocarbon receptor (AhR) triggers a cascade of defence responses against oxidative stress. By increasing AhR dependent cellular anti-oxidant activity, we tested the extent to which the cytotoxic effect of copper nanoparticles (CuNPs) is governed by oxidative stress. H4IIE rat hepatoma cells were challenged with high ROS levels after exposure to CuNPs, while the AhR-induced cellular anti-oxidant defence was simultaneously activated by the AhR ligand beta-Naphthoflavone (ßNF). Activation of phase II detoxification enzymes (as glutathione-S-transferases, GSTs) and anti-oxidants (glutathione, GSH) led to a complete abrogation of CuNP-induced ROS production. However, a concurrent reduction in cytotoxicity was not detected, thereby indicating that CuNPs exert non-oxidative stress mediated cytotoxic effects. Transmission electron microscopy analysis pointed to a direct physical perturbation of cellular structures by CuNPs, thus contributing to their cytotoxicity. Our observations highlight that distinct mechanisms underlie the toxicity of ions and NPs and indicate that while ROS elicitation is CuNP-specific, the cytotoxic action of these particles may not be directly related to their pro-oxidative activity. These findings have important implications with respect to the oxidative stress paradigm used to explain NP toxicity. © 2015 Elsevier Ireland Ltd. All rights reserved.

Bibliographic Details

Main Authors:	Connolly , Mona Elizabeth, Fernández Cruz, María Luisa, Navas Antón, José María
Format:	artículo biblioteca
Language:	English
Published:	Elsevier 2015
Subjects:	Copper nanoparticles (CuNPs), Oxidative stress, H4IIE, Aryl hydrocarbon receptor (AhR), ß-Naphthoflavone (ßNF), Co-incubation,
Online Access:	http://hdl.handle.net/20.500.12792/5944 http://hdl.handle.net/10261/291754
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