title: Nickel oxide nanoparticles exert cytotoxicity via oxidative stress and induce apoptotic response in human liver cells (HepG2).
abstract: Increasing use of nickel oxide nanoparticles (NiO NPs) necessitates an improved understanding of their potential impact on human health. Previously, toxic effects of NiO NPs have been investigated, mainly on airway cells. However, information on effect of NiO NPs on human liver cells is largely lacking. In this study, we investigated the reactive oxygen species (ROS) mediated cytotoxicity and induction of apoptotic response in human liver cells (HepG2) due to NiO NPs exposure. Prepared NiO NPs were crystalline and spherical shaped with an average diameter of 44 nm. NiO NPs induced cytotoxicity (cell death) and ROS generation in HepG2 cells in dose-dependent manner. Further, ROS scavenger vitamin C reduced cell death drastically caused by NiO NPs exposure indicating that oxidative stress plays an important role in NiO NPs toxicity. Micronuclei induction, chromatin condensation and DNA damage in HepG2 cells treated with NiO NPs suggest that NiO NPs induced cell death via apoptotic pathway. Quantitative real-time PCR analysis showed that following the exposure of HepG2 cells to NiO NPs, the expression level of mRNA of apoptotic genes (bax and caspase-3) were up-regulated whereas the expression level of anti-apoptotic gene bcl-2 was down-regulated. Moreover, activity of caspase-3 enzyme was also higher in NiO NPs treated cells. To the best of our knowledge this is the first report demonstrating that NiO NPs caused cytotoxicity via ROS and induced apoptosis in HepG2 cells, which is likely to be mediated through bax/bcl-2 pathway. This work warrants careful assessment of Ni NPs before their commercial and industrial applications.
authors.affiliation: King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia. Electronic address: maqusood@gmail.com.
authors.forename: Maqusood
authors.initials: M
authors.lastname: Ahamed
authors.forename: Daoud
authors.initials: D
authors.lastname: Ali
authors.forename: Hisham A
authors.initials: HA
authors.lastname: Alhadlaq
authors.forename: Mohd Javed
authors.initials: MJ
authors.lastname: Akhtar
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D056945:Hep G2 Cells; D006801:Humans; D053758:Nanoparticles / Q000633:toxicity*; D009532:Nickel / Q000633:toxicity*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D004785:Environmental Pollutants; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D009532:Nickel; C028007:nickel monoxide; D053148:Caspase 3
keywords: Apoptosis; Human health; Liver toxicity; NiO nanoparticles; ROS