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. 2024 Jun 6;14(1):13015.
doi: 10.1038/s41598-024-62877-4.

Yttrium oxide nanoparticles ameliorates calcium hydroxide and calcium titanate nanoparticles induced genomic DNA and mitochondrial damage, ROS generation and inflammation

Hanan R H Mohamed  1 , Ahmed H Farouk  2 , Salma H Elbasiouni  2 , Kirolls A Nasif  2 , Gehan Safwat  2
Affiliations

Yttrium oxide nanoparticles ameliorates calcium hydroxide and calcium titanate nanoparticles induced genomic DNA and mitochondrial damage, ROS generation and inflammation

Hanan R H Mohamed et al. Sci Rep. .

Abstract

Calcium hydroxide (Ca(OH)2NPs), calcium titanate (CaTiO3NPs) and yttrium oxide (Y2O3NPs) nanoparticles are prevalent in many industries, including food and medicine, but their small size raises concerns about potential cellular damage and genotoxic effects. However, there are very limited studies available on their genotoxic effects. Hence, this was done to investigate the effects of multiple administration of Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs on genomic DNA stability, mitochondrial membrane potential integrity and inflammation induction in mouse brain tissues. Mice were orally administered Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs at a dose level of 50 mg/kg b.w three times a week for 2 weeks. Genomic DNA integrity was studied using Comet assay and the level of reactive oxygen species (ROS) within brain cells was analyzed using 2,7 dichlorofluorescein diacetate dye. The expression level of Presenilin-1, tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) genes and the integrity of the mitochondrial membrane potential were also detected. Oral administration of Ca(OH)2NPs caused the highest damage to genomic DNA and mitochondrial membrane potential, less genomic DNA and mitochondrial damage was induced by CaTiO3NPs administration while administration of Y2O3NPs did not cause any remarkable change in the integrity of genomic DNA and mitochondrial membrane potential. Highest ROS generation and upregulation of presenilin-1, TNF-α and IL-6 genes were also observed within the brain cells of mice administrated Ca(OH)2NPs but Y2O3NPs administration almost caused no changes in ROS generation and genes expression compared to the negative control. Administration of CaTiO3NPs alone slightly increased ROS generation and the expression level of TNF-α and IL-6 genes. Moreover, no remarkable changes in the integrity of genomic DNA and mitochondrial DNA potential, ROS level and the expression level of presenilin-1, TNF-α and IL-6 genes were noticed after simultaneous coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs. Coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs mitigated Ca(OH)2NPs and CaTiO3NPs induced ROS generation, genomic DNA damage and inflammation along with restoring the integrity of mitochondrial membrane potential through Y2O3NPs scavenging free radicals ability. Therefore, further studies are recommended to study the possibility of using Y2O3NPs to alleviate Ca(OH)2NPs and CaTiO3NPs induced genotoxic effects.

Keywords: Calcium hydroxide; Calcium titanate; Genotoxicity; Mitochondrial membrane potential; Nanoparticles; ROS generation; Yttrium oxide.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
ROS level using 2,7-DCFH-DA dye within the brain cells of (a) Negative control group, (b) Ca(OH)2NPs administered group, (c) CaTiO3NPs administered group, (d) Y3O2NPs administered group and (e) group administered Ca(OH)2NPs, CaTiO3NPs and Y3O2NPs simultaneously.
Figure 2
Figure 2
Representative photomicrograph for the observed Comet intact and damaged nuclei in the brain tissues of negative control group and Ca(OH)2NPs, CaTiO3NPs or/and Y3O2NPs administered groups. (A) Intact nuclei (B) Damaged nuclei.
Figure 3
Figure 3
Integrity of mitochondrial membrane potential using Rhodamine dye within the brain cells of (a) Negative control group, (b) Ca(OH)2NPs administered group, (c) CaTiO3NPs administered group, (d) Y3O2NPs administered group and (e) group administered Ca(OH)2NPs, CaTiO3NPs and Y3O2NPs simultaneously.
Figure 4
Figure 4
Expression level of Presenilin-1, TNF-α and IL-6 genes in in the brain tissues of the negative control group and groups orally administered Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs. Results are expressed as mean ± SD and were analyzed using one-way analysis of variance followed by Duncan’s test to test the similarity between the control and three treated groups. Means with different superscript letters indicates statistical significant difference at p < 0.05 between the compared groups for the same gene.
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