title: Zinc ferrite nanoparticle-induced cytotoxicity and oxidative stress in different human cells.
abstract: BACKGROUND
  Zinc ferrite nanoparticles (NPs) have shown potential to be used in biomedical field such as magnetic resonance imaging and hyperthermia. However, there is limited information concerning the biological response of zinc ferrite NPs. This study was designed to evaluate the cytotoxicity of zinc ferrite NPs in three widely used in vitro cell culture models: human lung epithelial (A549), skin epithelial (A431) and liver (HepG2) cells. Zinc ferrite NPs were characterized by electron microscopy and dynamic light scattering. Cell viability, cell membrane damage, reactive oxygen species (ROS), glutathione (GSH), mitochondrial membrane potential (MMP), transcriptional level of apoptotic genes were determined in zinc ferrite NPs exposed cells.
  
  
  RESULTS
  Zinc ferrite NPs were almost spherical shaped with an average size of 44 nm. Zinc ferrite NPs induced dose-dependent cytotoxicity (MTT and LDH) and oxidative stress (ROS and GSH) in all three types of cells in the dosage range of 10-40 µg/ml. Transcriptional level of tumor suppressor gene p53 and apoptotic genes (bax, caspase-3 and caspase-9) were up-regulated while the anti-apoptotic gene bcl-2 was down-regulated in cells after zinc ferrite NPs exposure. Furthermore, higher activity of caspase-3 and caspase-9 enzymes was also observed in zinc ferrite NPs treated cells. ROS generation, MMP loss and cell death in all three types of cells were abrogated by N-acetyl cysteine (ROS scavenger), which suggests that oxidative stress might be one of the plausible mechanisms of zinc ferrite NPs cytotoxicity. It is worth mentioning that there was marginally difference in the sensitivity of three cell lines against zinc ferrite NPs exposure. Cytotoxicity of zinc ferrite NPs were in following order; A549 > HepG2 > A431.
  
  
  CONCLUSIONS
  Altogether, zinc ferrite NPs induced cytotoxicity and oxidative stress in A549, A431 and HepG2 cells, which is likely to be mediated through ROS generation. This study warrants further investigation to explore the potential mechanisms of toxicity of zinc ferrite NPs in normal cells as well as in animal models.
authors.affiliation: Department of Physics and Astronomy, College of Science, King Saud University, Riyadh, 11451 Saudi Arabia.
authors.forename: Hisham A
authors.initials: HA
authors.lastname: Alhadlaq
authors.affiliation: King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, 11451 Saudi Arabia.
authors.forename: Mohd Javed
authors.initials: MJ
authors.lastname: Akhtar
authors.affiliation: King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, 11451 Saudi Arabia.
authors.forename: Maqusood
authors.initials: M
authors.lastname: Ahamed
keywords: A431; A549; Cytotoxicity; HepG2; Human health; Reactive oxygen species; Zinc ferrite nanoparticles