title: Concentration-dependent induction of reactive oxygen species, cell cycle arrest and apoptosis in human liver cells after nickel nanoparticles exposure.
abstract: Due to advent of nanotechnology, nickel nanoparticles (Ni NPs) are increasingly recognized for their utility in various applications including catalysts, sensors and electronics. However, the environmental and human health effects of Ni NPs have not been fully investigated. In this study, we examined toxic effects of Ni NPs in human liver (HepG2) cells. Ni NPs were prepared and characterized by X-ray diffraction, transmission electron microscopy and dynamic light scattering. We observed that Ni NPs (size, ∼28 nm; concentration range, 25-100 μg/mL) induced cytotoxicity in HepG2 cells and degree of induction was concentration-dependent. Ni NPs were also found to induce oxidative stress in dose-dependent manner evident by induction of reactive oxygen species and depletion of glutathione. Cell cycle analysis of cells treated with Ni NPs exhibited significant increase of apoptotic cell population in subG1 phase. Ni NPs also induced caspase-3 enzyme activity and apoptotic DNA fragmentation. Upregulation of cell cycle checkpoint gene p53 and bax/bcl-2 ratio with a concomitant loss in mitochondrial membrane potential suggested that Ni NPs induced apoptosis in HepG2 cells was mediated through mitochondrial pathway. This study warrants that applications of Ni NPs should be carefully assessed as to their toxicity to human health.
authors.affiliation: Department of Zoology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
authors.forename: Javed
authors.initials: J
authors.lastname: Ahmad
authors.forename: Hisham A
authors.initials: HA
authors.lastname: Alhadlaq
authors.forename: Maqsood A
authors.initials: MA
authors.lastname: Siddiqui
authors.forename: Quaiser
authors.initials: Q
authors.lastname: Saquib
authors.forename: Abdulaziz A
authors.initials: AA
authors.lastname: Al-Khedhairy
authors.forename: Javed
authors.initials: J
authors.lastname: Musarrat
authors.forename: Maqusood
authors.initials: M
authors.lastname: Ahamed
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000032:analysis / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D053938:DNA Fragmentation; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D009499:Neutral Red; D009532:Nickel / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D004396:Coloring Agents; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D009499:Neutral Red; D009532:Nickel; D053148:Caspase 3; C022616:thiazolyl blue; D005978:Glutathione
keywords: cell cycle; health effects; human liver cells; nickel nanoparticles; oxidative stress