Zinc oxide nanoparticles exposure-induced oxidative stress restricts cranial neural crest development during chicken embryogenesis.

Zinc oxide Nanoparticles (ZnO NPs) are widely used as emerging materials in agricultural and food-related fields, which exists potential safety hazards to public health and environment while bringing an added level of convenience to our original life. It has been proved that ZnO NPs could be taken up by pregnant women and passed through human placental barrier. However, the toxic potential for embryo development remains largely unanswered. In this study, we discovered that ZnO NPs caused the cytotoxicity in vitro. Inhibition of free Zn ²⁺ ions in solution by EDTA or inhibition of Zn ²⁺ ions absorption by CaCl ₂ could partially eliminate ZnO NPs-mediated cell toxicity, though not redeem completely. This indicated that both nanoparticles and the release of Zn ²⁺ ions were involved in ZnO NPs-mediated cytotoxicity. In addition, we also found that both nanoparticles and Zn ²⁺ ion release triggered reactive oxygen species (ROS) production, which further induced cell toxicity, inflammation and apoptosis, which are mediated by NF-κB signaling cascades and the mitochondria dysfunction, respectively. Eventually, these events lead to the suppressed production and migration of cranial neural crest cells (CNCCs), which subsequently prompts the craniofacial defects in chicken embryos. The application of the antioxidant N-Acetyl-L-cysteine (NAC) rescued the ZnO NPs-induced cell toxicity and malformation of the CNCCs, which further verified our hypothesis. Our results revealed the relevant mechanism of ZnO NPs exposure-inhibited the development of CNCCs, which absolutely contribute to assess the risk of nanoparticles application.
Competing Interests: Declaration of competing interests The authors report no conflict of interest. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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