5584
Nahla Nabil Kamel Ali
Biological studies on Zinc Oxide Nanoparticles In Vitro and In Vivo
ZnO NPs , toxicity , antioxident, , (HepG2 , neurotransmitters
Although the application of Zinc Oxide in the form of nanoparticles is a common trend nowadays, extensive research on their toxicity is highly demanded to clarify their mechanism of action. Therefore different sizes and doses of ZnO NPs are used in this study aiming to attain a dose correlated with a particle size that could be considerably of least toxicity for biomedical applications. The present study, two doses of ZnO NPs (50 and 150 mg/kg. B.wt) for each of three different particle sizes (14, 30, 50 nm) were administered to mice for 14 consecutive days. Biochemical and histopathological investigations were performed to select the least toxic dose that compatible with desired particle size for biomedical studies to ascertain their activity against cancer cells. Also, Comet and molecular analysis (qRT-PCR) assays were performed on liver tissues. The cytotoxic effect of different sizes (14nm, 30 nm and 50nm) of ZnO NPs on liver cancer cell lines (HepG2, HuH7 cells) vs normal cells (THLE2 cells) was elucidated by MTT and multiple assays. The results showed variable disorders in the different parameters. The most toxic effect was revealed using the highest dose (150 mg/kg) with particle size 30nm. This was demonstrated in a significant increase in liver coefficients as well as in serum liver function enzymes. Also, the hepatic defense mechanisms showed significant disorders in the different antioxidants measured and in hepatic DNA damage using comet assay. On the molecular level, this dose and particle size showed most up regulation in Bax and caspase-3 gene expressions and down-regulated in Bcl-2. Moreover, ZnO-NPs also showed the most significant depletion in brain neurotransmitters (dopamine and serotonin) and elevation in noradrenaline level. The histopathological studies revealed that using particle size 14nm with a dose of 50mg/kg caused the least toxic effect on all mice organs. In vitro studies, IC50 values on cancer cell lines (HepG2 and HuH7) recorded variable cytotoxic effects for different sizes whereas no cytotoxic effect was observed on normal cell line (THLE2). The highest cytotoxic activity was 0.05 µg/ml using particle size 14 nm. The oxidative stress in culture cells elicited a reduction in reduced glutathione with increase in lipid peroxides and Caspase-3. In addition, RT-PCR revealed a significant up- regulation in caspase-3 gene expression. It could be concluded that least toxicity using ZnO NPs was achieved using 14nm particle size with a dose of 50mg/kg which can be recommended for biomedical applications in cancer research.
2019
Ph.d
Beni Suef
Science