title: Oxidative stress induced by pure and iron-doped amorphous silica nanoparticles in subtoxic conditions.
abstract: 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.
authors.affiliation: Unit for Lung Toxicology, Katholieke Universiteit Leuven, Herestraat 49, O&N1-706, 3000 Leuven, Belgium.
authors.forename: Dorota
authors.initials: D
authors.lastname: Napierska
authors.forename: Virginie
authors.initials: V
authors.lastname: Rabolli
authors.forename: Leen C J
authors.initials: LC
authors.lastname: Thomassen
authors.forename: David
authors.initials: D
authors.lastname: Dinsdale
authors.forename: Catherine
authors.initials: C
authors.lastname: Princen
authors.forename: Laetitia
authors.initials: L
authors.lastname: Gonzalez
authors.forename: Katrien L C
authors.initials: KL
authors.lastname: Poels
authors.forename: Micheline
authors.initials: M
authors.lastname: Kirsch-Volders
authors.forename: Dominique
authors.initials: D
authors.lastname: Lison
authors.forename: Johan A
authors.initials: JA
authors.lastname: Martens
authors.forename: Peter H
authors.initials: PH
authors.lastname: Hoet
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002474:Cell-Free System; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D007501:Iron / Q000737:chemistry*; D015227:Lipid Peroxidation / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D017665:Hydroxyl Radical; D012822:Silicon Dioxide; D007501:Iron; D051547:Heme Oxygenase-1; D005978:Glutathione