title: Oxidative mechanisms contribute to nanosize silican dioxide-induced developmental neurotoxicity in PC12 cells.
abstract: Neurotoxicity was investigated in nano-SiO2-treated cultured PC12 cells, an in vitro neuronal cell model, in order to define a relatively safe dose range for its application. The following were observed in the present study: (1) A dose-dependent increase in the level of reactive oxygen species (ROS) with a corresponding decrease in the level of glutathione (R2=0.965) suggesting 20- and 50-nm SiO2-induced free radical generation and glutathione depletion. (2) A dose- and time-dependent decrease in cell viability that was associated with elevation of ROS level, especially after 24-h nano-SiO2 exposure (R2=0.965), suggesting the role of oxidative stress on nano-SiO2 induced cell death. (3) An increase in the level of thiobarbituric-acid reactive species that correlated reversely with cell viability of the PC12 cells treated with nano-SiO2 (R2=0.945) suggesting nano-SiO2-induced membrane damage caused by lipid peroxidation. (4) A dose-dependent increase in sub-G1 population in SiO2-exposed cells along with cell shrinkage and nuclear condensation from morphological examination suggesting nano-SiO2-induced cell apoptosis. Furthermore, nano-SiO2 exposure diminished the ability of neurite extension in response to nerve growth factor in treated PC12 cells. In summary, SiO2 nanoparticle exposure resulted in dose-dependent neurotoxicity in cultured PC12 cells that was probably associated with oxidative stress and induced apoptosis.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.forename: Changping
authors.initials: C
authors.lastname: Jiao
authors.forename: Jianwen
authors.initials: J
authors.lastname: Liu
authors.forename: Huihui
authors.initials: H
authors.lastname: Yuan
authors.forename: Minbo
authors.initials: M
authors.lastname: Lan
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress; D016716:PC12 Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012822:Silicon Dioxide / Q000633:toxicity*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D012822:Silicon Dioxide; D020932:Nerve Growth Factor; D005978:Glutathione