title: Nanotoxicity of pure silica mediated through oxidant generation rather than glutathione depletion in human lung epithelial cells.
abstract: Though, oxidative stress has been implicated in silica nanoparticles induced toxicity both in vitro and in vivo, but no similarities exist regarding dose-response relationship. This discrepancy may, partly, be due to associated impurities of trace metals that may present in varying amounts. Here, cytotoxicity and oxidative stress parameters of two sizes (10 nm and 80 nm) of pure silica nanoparticles was determined in human lung epithelial cells (A549 cells). Both sizes of silica nanoparticles induced dose-dependent cytotoxicity as measured by MTT [3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and lactate dehydrogenase (LDH) assays. Silica nanoparticles were also found to induce oxidative stress in dose-dependent manner indicated by induction of reactive oxygen species (ROS) generation, and membrane lipid peroxidation (LPO). However, both sizes of silica nanoparticles had little effect on intracellular glutathione (GSH) level and the activities of glutathione metabolizing enzymes; glutathione reductase (GR) and glutathione peroxidase (GPx). Buthionine-[S,R]-sulfoximine (BSO) plus silica nanoparticles did not result in significant GSH depletion than that caused by BSO alone nor N-acetyl cysteine (NAC) afforded significant protection from ROS and LPO induced by silica nanoparticles. The rather unaltered level of GSH is also supported by finding no appreciable alteration in the level of GR and GPx. Our data suggest that the silica nanoparticles exert toxicity in A549 cells through the oxidant generation (ROS and LPO) rather than the depletion of GSH.
authors.affiliation: Fibre Toxicology Division, Indian Institute of Toxicology Research (CSIR), Lucknow, UP, India.
authors.forename: Mohd Javed
authors.initials: MJ
authors.lastname: Akhtar
authors.forename: Maqusood
authors.initials: M
authors.lastname: Ahamed
authors.forename: Sudhir
authors.initials: S
authors.lastname: Kumar
authors.forename: Huma
authors.initials: H
authors.lastname: Siddiqui
authors.forename: Govil
authors.initials: G
authors.lastname: Patil
authors.forename: Mohd
authors.initials: M
authors.lastname: Ashquin
authors.forename: Iqbal
authors.initials: I
authors.lastname: Ahmad
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000166:cytology / Q000187:drug effects; D008563:Membrane Lipids / Q000378:metabolism; D053758:Nanoparticles; D016877:Oxidants / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D008563:Membrane Lipids; D016877:Oxidants; D017382:Reactive Oxygen Species; D019328:Buthionine Sulfoximine; D012822:Silicon Dioxide; D005978:Glutathione; D000111:Acetylcysteine