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

Intensive uses of Calcium hydroxide (Ca(OH)NPs), calcium titanate (CaTiONPs) and yttrium oxide (YONPs) 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)NPs, CaTiONPs or/and YONPs administration on the genotoxicityand oxidative stress induction in mice hepatic tissue. Mice were orally administered Ca(OH)NPs, CaTiONPs and YONPs 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)NPs or CaTiONPs alone together with high Ca(OH)NPs induced reactive oxygen species (ROS) generation and a slight CaTiONPs induced ROS production were highly decreased after simultaneous coadministration of administration of YONPs with Ca(OH)NPs and CaTiONPs up to the negative control level. Oral administration of YONPs 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)NPs 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 CaTiONPs and YONPs separately or simultaneously together with Ca(OH)NPs. Conclusion: Ca(OH)NPs 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 CaTiONPs administration. However, administration of YONPs alone was non-genotoxic and coadministration of YONPs with Ca(OH)NPs and CaTiONPs restored genomic DNA integrity and normal expression of apoptotic p53 and protective HSP-70 genes disrupted by Ca(OH)NPs and CaTiONPs. Thus co-administration of YONPs with Ca(OH)NPs and CaTiONPs is recommended to counter Ca(OH)NPs and CaTiONPs induced genotoxicity and oxidative stress.