Toxicity assessment of zinc oxide nanoparticles in mice: Correlation between different doses and particle sizes

ZnO NPs are previously reported to have diverse toxic effects. However, this study aims to attain a safe dose correlated with a small particle size of these NPs to be used in biomedical applications in further research. Investigation of toxicity-induced disorders using different sizes and doses of ZnO NPs and selection of the most convenient dose and size to be utilized in medical applications. Two doses of ZnO NPs (50 and 150 mg/kg. B.wt) for each of three different particle sizes (14, 30, 50 nm) were administrated to mice for 14 consecutive days. Biochemical and histopathological investigations were performed to confirm the toxicity of ZnO NPs. Comet and qRT-PCR assays were performed on liver tissues. Data were analyzed using SPSS coupled with Co-Stat (version 8). A significant increase in both liver and kidney coefficients as well as in serum liver function enzymes was obtained using the higher dose of ZnO NPs. Also, the hepatic defense mechanisms showed significant disorders in the different antioxidants measured. Comet assay revealed a significant hepatic DNA damage. On the molecular level, an up regulation in Bax and caspase-3 gene expressions were observed while, BcI-2 was down-regulated. ZnO-NPs also showed a significant depletion in brain neurotransmitters (dopamine and serotonin) and an elevation in noradernaline level. The higher dose of ZnO NPs using particle size 30 nm induced the most toxic effect on liver and brain tissues. While the lower dose using 14nm was considerably safe for therapeutic applications.