Neurotoxicity and biomarkers of zinc oxide nanoparticles in main functional brain regions and dopaminergic neurons

Manufactured zinc oxide nanoparticles (Nano-ZnO) are being used increasingly in many fields owing to their excellent physicochemical properties. Consequently, biosecurity has become a growing concern for human health and the environment. In the present study, Nano-ZnO neurotoxicity was investigated...

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Veröffentlicht in:The Science of the total environment 2020-02, Vol.705, p.135809, Article 135809
Hauptverfasser: Liu, Huanliang, Yang, Honglian, Fang, Yanjun, Li, Kang, Tian, Lei, Liu, Xiaohua, Zhang, Wei, Tan, Yizhe, Lai, Wenqing, Bian, Liping, Lin, Bencheng, Xi, Zhuge
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Sprache:eng
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Zusammenfassung:Manufactured zinc oxide nanoparticles (Nano-ZnO) are being used increasingly in many fields owing to their excellent physicochemical properties. Consequently, biosecurity has become a growing concern for human health and the environment. In the present study, Nano-ZnO neurotoxicity was investigated in vivo and in vitro. In vivo results showed that Nano-ZnO particles delivered through intranasal instillation were translocated to the brain, specifically deposited in the olfactory bulb, hippocampus, striatum, and cerebral cortex, and caused ultrastructural changes, oxidative damage, inflammatory responses, and histopathological damages there, which may be important for inducing Nano-ZnO neurotoxicity. Further in vitro studies on PC12 cell line illustrated that exposure to Nano-ZnO for 6 h affected cell morphology, decreased cell viability, increased lactate dehydrogenase and oxidative stress activity levels, impaired mitochondrial function, and disturbed the cell cycle. In addition, Nano-ZnO could destroy neuronal structure by affecting cytoskeleton proteins (tubulin-α, tubulin-β and NF-H), resulting in the interruption of connection between nerve cells, which lead to nervous system function damage. Meanwhile, Nano-ZnO could induce neuronal repair and regeneration disorders by affecting the growth-related protein GAP-43 and delayed neurotoxicity by affecting the calcium/calcium-regulated kinase (CAMK2A/CAMK2B protein) signaling pathway. [Display omitted] •Nano-ZnO can be transported via the olfactory nerve pathways into the brain tissue.•Nano-ZnO can deposit in olfactory bulb, hippocampus, striatum, and cerebral cortex.•Nano-ZnO can cause toxic damage to crucial functional sub-brain regions.•Nano-ZnO can damage neuronal mitochondrial function by oxidative stress mechanism.•Nano-ZnO can reduce the expression of CAMKII, GAP43, tubulin, and NF-H in neurons.
ISSN:0048-9697
1879-1026
DOI:10.1016/j.scitotenv.2019.135809