Oxidative Stress Induced by Pure and Iron-Doped Amorphous Silica Nanoparticles in Subtoxic Conditions

• Published in: Chemical research in toxicology 2012-04, Vol.25 (4), p.828-837
• Main Authors: Napierska, Dorota, Rabolli, Virginie, Thomassen, Leen C. J, Dinsdale, David, Princen, Catherine, Gonzalez, Laetitia, Poels, Katrien L. C, Kirsch-Volders, Micheline, Lison, Dominique, Martens, Johan A, Hoet, Peter H
• Format: Article
• Language: English
• Subjects: Cell Line; Cell Survival - drug effects; Cell-Free System; Gene Expression Regulation; Glutathione - metabolism; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Humans; Hydroxyl Radical - metabolism; Iron - chemistry; Lipid Peroxidation - drug effects; Nanoparticles - chemistry; Nanoparticles - toxicity; Oxidative Stress - drug effects; Particle Size; Silicon Dioxide - chemistry
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/tx200361v

Amorphous silica nanoparticles (SiO2-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 SiO2-NPs in different cell types. The present study was designed to examine the association of oxidative stress markers with SiO2-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 SiO2-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 μg/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 SiO2-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 μg/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.