Genotoxicity and oxidative stress induction by calcium hydroxide, calcium titanate or/and yttrium oxide nanoparticles in mice

Abstract

Intensive uses of Calcium hydroxide (Ca(OH)₂NPs), calcium titanate (CaTiO₃NPs) and yttrium oxide (Y₂O₃NPs) nanoparticles increase their environmental release and human exposure separately or together through contaminated air, water and food. However, too limited data are available on their genotoxicity. Therefore, this study explored the effect of Ca(OH)₂NPs, CaTiO₃NPs or/and Y₂O₃NPs administration on the genotoxicityand oxidative stress induction in mice hepatic tissue. Mice were orally administered Ca(OH)₂NPs, CaTiO₃NPs and Y₂O₃NPs separately or simultaneously together at a dose level of 50 mg/kg b.w. for two successive weeks (3 days per week). Marked induction of DNA damage noticed after oral administration of Ca(OH)₂NPs or CaTiO₃NPs alone together with high Ca(OH)₂NPs induced reactive oxygen species (ROS) generation and a slight CaTiO₃NPs induced ROS production were highly decreased after simultaneous coadministration of administration of Y₂O₃NPs with Ca(OH)₂NPs and CaTiO₃NPs up to the negative control level. Oral administration of Y₂O₃NPs alone also did not cause observable changes in the genomic DNA integrity and the ROS generation level compared to the negative control levels. Similarly, significant elevations in P53 gene expression and high reductions in Kras and HSP-70 genes expression were observed only after administration of Ca(OH)₂NPs alone, while, remarkable increases in the Kras and HSP-70 genes expression and non-significant changes in p53 gene expression were noticed after administration of CaTiO₃NPs and Y₂O₃NPs separately or simultaneously together with Ca(OH)₂NPs. Conclusion: Ca(OH)₂NPs exhibited the highest genotoxic effect through oxidative stress induction and disruption of apoptotic (p53 and Kras) and protective (HSP-70) genes expression. Slight DNA damage was noticed after CaTiO₃NPs administration. However, administration of Y₂O₃NPs alone was non-genotoxic and coadministration of Y₂O₃NPs with Ca(OH)₂NPs and CaTiO₃NPs restored genomic DNA integrity and normal expression of apoptotic p53 and protective HSP-70 genes disrupted by Ca(OH)₂NPs and CaTiO₃NPs. Thus co-administration of Y₂O₃NPs with Ca(OH)₂NPs and CaTiO₃NPs is recommended to counter Ca(OH)₂NPs and CaTiO₃NPs induced genotoxicity and oxidative stress.