title: Silver nanoparticles induced neurotoxicity through oxidative stress in rat cerebral astrocytes is distinct from the effects of silver ions.
abstract: The rapid development of silver nanoparticles (AgNPs) based products has raised increasing concerns in view of their potential hazardous risks to the environment and human health. The roles of the released silver ions in AgNPs induced cytotoxicities are being hotly debated. Using rat cerebral astrocytes, the neurotoxicological effects of AgNPs and silver ions were investigated. Acute toxicity based on Alamar Blue assay showed that silver ions were considerably more toxic than AgNPs. Comparative studies indicated that AgNPs increased caspase activities and induced cell apoptosis under cytotoxic level of exposures, while silver ions compromised cell membrane integrity and dominantly caused cell necrosis. Cellular internalization of silver provided the basis for the cytotoxicities of these two silver species. In contrast to silver ions, intracellular reactive oxygen species (ROS) generation occurred in time- and concentration-dependent manners in astrocytes upon AgNPs stimulation, which caused subsequent c-Jun N-terminal kinases (JNK) phosphorylation and promoted the programmed cell death. Non-cytotoxic level of AgNPs exposure increased multiple cytokines secretion from the astrocytes, indicating that AgNPs were potentially involved in neuroinflammation. This effect was independent of silver ions as well. The distinct toxicological effects caused by AgNPs and silver ions provided the solid proofs for the particle-specific effects which should be concerned regarding the accurate assessment of AgNPs exposure risks.
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China.
authors.forename: Nuoya
authors.initials: N
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China; School of Earth and Space Science, University of Science and Technology of China, Anhui 230026, PR China.
authors.forename: Ruoxi
authors.initials: R
authors.lastname: Wen
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China; Institute of Chemical Safety, Chinese Academy of Inspection and Quarantine, Beijing 100176, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Center for Biological Imaging, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China.
authors.forename: Ligang
authors.initials: L
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China. Electronic address: zhouqf@rcees.ac.cn.
authors.forename: Qunfang
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China.
authors.forename: Guibin
authors.initials: G
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology*; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity*; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000378:metabolism / Q000633:toxicity*
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D012834:Silver; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Astrocyte; Neurotoxicity; Particle effect; Silver ion release; Silver nanoparticle