Toxicity of different zinc oxide nanomaterials and dose-dependent onset and development of Parkinson’s disease-like symptoms induced by zinc oxide nanorods

With the increasing applications in various fields, the release and accumulation of zinc oxide (ZnO) nanomaterials ultimately lead to unexpected consequences to environment and human health. Therefore, toxicity comparison among ZnO nanomaterials with different shape/size and their adverse effects need better characterization. Here, we utilized zebrafish larvae and human neuroblastoma cells SH-SY5Y to compare the toxic effects of ZnO nanoparticles (ZnO NPs), short ZnO nanorods (s-ZnO NRs), and long ZnO NRs (l-ZnO NRs). We found their developmental- and neuro-toxicity levels were similar, where the smaller sizes showed slightly higher toxicity than the larger sizes. The developmental neurotoxicity of l-ZnO NRs (0.1, 1, 10, 50, and 100 μg/mL) was further investigated since they had the lowest toxicity. Our results indicated that l-ZnO NRs induced developmental neurotoxicity with hallmarks linked to Parkinson’s disease (PD)-like symptoms at relatively high doses, including the disruption of locomotor activity as well as neurodevelopmental and PD responsive genes expression, and the induction of dopaminergic neuronal loss and apoptosis in zebrafish brain. l-ZnO NRs activated reactive oxygen species production, whose excessive accumulation triggered mitochondrial damage and mitochondrial apoptosis, eventually leading to PD-like symptoms. Collectively, the developmental- and neuro-toxicity of ZnO nanomaterials was identified, in which l-ZnO NRs harbors a remarkably potential risk for the onset and development of PD at relatively high doses, stressing the discretion of safe range in view of nano-ZnO exposure to ecosystem and human beings.