title: Apoptosis induction by silica nanoparticles mediated through reactive oxygen species in human liver cell line HepG2.
abstract: Silica nanoparticles are increasingly utilized in various applications including agriculture and medicine. In vivo studies have shown that liver is one of the primary target organ of silica nanoparticles. However, possible mechanisms of hepatotoxicity caused by silica nanoparticles still remain unclear. In this study, we explored the reactive oxygen species (ROS) mediated apoptosis induced by well-characterized 14nm silica nanoparticles in human liver cell line HepG2. Silica nanoparticles (25-200μg/ml) induced a dose-dependent cytotoxicity in HepG2 cells. Silica nanoparticles were also found to induce oxidative stress in dose-dependent manner indicated by induction of ROS and lipid peroxidation and depletion of glutathione (GSH). Quantitative real-time PCR and immunoblotting results showed that both the mRNA and protein expressions of cell cycle checkpoint gene p53 and apoptotic genes (bax and caspase-3) were up-regulated while the anti-apoptotic gene bcl-2 was down-regulated in silica nanoparticles treated cells. Moreover, co-treatment of ROS scavenger vitamin C significantly attenuated the modulation of apoptotic markers along with the preservation of cell viability caused by silica nanoparticles. Our data demonstrated that silica nanoparticles induced apoptosis in human liver cells, which is ROS mediated and regulated through p53, bax/bcl-2 and caspase pathways. This study suggests that toxicity mechanisms of silica nanoparticles should be further investigated at in vivo level.
authors.affiliation: Department of Zoology, College of Science, King Saud University, Saudi Arabia. maqusood@gmail.com
authors.forename: Javed
authors.initials: J
authors.lastname: Ahmad
authors.forename: Maqusood
authors.initials: M
authors.lastname: Ahamed
authors.forename: Mohd Javed
authors.initials: MJ
authors.lastname: Akhtar
authors.forename: Salman A
authors.initials: SA
authors.lastname: Alrokayan
authors.forename: Maqsood A
authors.initials: MA
authors.lastname: Siddiqui
authors.forename: Javed
authors.initials: J
authors.lastname: Musarrat
authors.forename: Abdulaziz A
authors.initials: AA
authors.lastname: Al-Khedhairy
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008854:Microscopy, Electron; D053758:Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012822:Silicon Dioxide / Q000633:toxicity*; D013052:Spectrometry, X-Ray Emission; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014961:X-Ray Diffraction; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D012822:Silicon Dioxide; D020169:Caspases; D005978:Glutathione