Oxidative stress induced by pure and iron-doped amorphous silica nanoparticles in subtoxic conditions.

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Napierska D, Rabolli V, Thomassen LC, Dinsdale D, Princen C, Gonzalez L, Poels KL, Kirsch-Volders M, Lison D, Martens JA, Hoet PH

Oxidative stress induced by pure and iron-doped amorphous silica nanoparticles in subtoxic conditions.

Chem Res Toxicol. 2012 Apr 16;25(4):828-37. doi: 10.1021/tx200361v. Epub 2012 Mar 13.

PubMed ID
22263782 [ View in PubMed
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Abstract

Amorphous silica nanoparticles (SiO(2)-NPs) have found broad applications in industry and are currently intensively studied for potential uses in medical and biomedical fields. Several studies have reported cytotoxic and inflammatory responses induced by SiO(2)-NPs in different cell types. The present study was designed to examine the association of oxidative stress markers with SiO(2)-NP induced cytotoxicity in human endothelial cells. We used pure monodisperse amorphous silica nanoparticles of two sizes (16 and 60 nm; S16 and S60) and a positive control, iron-doped nanosilica (16 nm; SFe), to study the generation of hydroxyl radicals (HO.) in cellular-free conditions and oxidative stress in cellular systems. We investigated whether SiO(2)-NPs could influence intracellular reduced glutathione (GSH) and oxidized glutathione (GSSG) levels, increase lipid peroxidation (malondialdehyde (MDA) and 4-hydroxyalkenal (HAE) concentrations), and up-regulate heme oxygenase-1 (HO-1) mRNA expression in the studied cells. None of the particles, except SFe, produced ROS in cell-free systems. We found significant modifications for all parameters in cells treated with SFe nanoparticles. At cytotoxic doses of S16 (40-50 mug/mL), we detected weak alterations of intracellular glutathione (4 h) and a marked induction of HO-1 mRNA (6 h). Cytotoxic doses of S60 elicited similar responses. Preincubation of cells being exposed to SiO(2)-NPs with an antioxidant (5 mM N-acetylcysteine, NAC) significantly reduced the cytotoxic activity of S16 and SFe (when exposed up to 25 and 50 mug/mL, respectively) but did not protect cells treated with S60. Preincubation with NAC significantly reduced HO-1 mRNA expression in cells treated with SFe but did not have any effect on HO-1 mRNA level in cell exposed to S16 and S60. Our study demonstrates that the chemical composition of the silica nanoparticles is a dominant factor in inducing oxidative stress.