Apoptotic and DNA-damaging effects of yttria-stabilized zirconia nanoparticles on human skin epithelial cells

Int J Nanomedicine. 2019 Sep 2:14:7003-7016. doi: 10.2147/IJN.S212255. eCollection 2019.

Abstract

Background: Yttria-stabilized zirconia (Y2O3/ZrO2) nanoparticles are one of the important nanoparticles extensively used in manufacturing of plastics, textiles, catalyst, etc. Still, the cytotoxic and apoptotic effects of yttria-stabilized zirconia nanoparticles have not been well identified on human skin keratinocyte (HaCaT) cells. Therefore, in this study, we have designed to examine the cytotoxic potential of yttria-stabilized zirconia nanoparticles in HaCaT cells.

Methods: Prior to treatment, the yttria-stabilized zirconia nanoparticles were characterized by using different advanced instruments viz. dynamic light scattering (DLS), scanning electron microscope (SEM) and transmission electron microscope (TEM). Cell viability of HaCaT cells was measured by using MTS and NRU assays and viability of cells was reduced in a dose- and time-dependent manner.

Results: Reduction in the viability of cells was correlated with the rise of reactive oxygen species generation, increased caspase-3, mitochondria membrane potential and evidence of DNA strand breakage. These were consistent with the possibility that mitochondria damage can play a significant role in the cytotoxic response. Moreover, the activity of oxidative enzymes such as lipid peroxide (LPO) was increased and glutathione was reduced in HaCaT cells exposed with yttria-stabilized zirconia nanoparticles. It is also important to indicate that HaCaT cells appear to be more susceptible to yttria-stabilized zirconia nanoparticles exposure after 24 hrs.

Conclusion: This result provides a dose- and time-dependent apoptosis and genotoxicity of yttria-stabilized zirconia nanoparticles in HaCaT cells.

Keywords: HaCaT cells; apoptosis; geno toxicity; oxidative stress; yttria-stabilized zirconia nanoparticles.

MeSH terms

  • Acetylcysteine / pharmacology
  • Apoptosis* / drug effects
  • Cell Line
  • Cell Shape / drug effects
  • Cell Survival / drug effects
  • DNA Breaks, Double-Stranded / drug effects
  • DNA Damage*
  • DNA Fragmentation / drug effects
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism
  • Glutathione / metabolism
  • Humans
  • Intracellular Membranes / drug effects
  • Intracellular Membranes / metabolism
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / ultrastructure
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism
  • Skin / cytology*
  • Yttrium / chemistry*
  • Zirconium / chemistry*

Substances

  • Reactive Oxygen Species
  • Yttrium
  • Zirconium
  • Glutathione
  • zirconium oxide
  • Acetylcysteine
  • yttria