<p>Nd<sub>2</sub>O<sub>3</sub> Nanoparticles Induce Toxicity and Cardiac/Cerebrovascular Abnormality in Zebrafish Embryos via the Apoptosis Pathway</p>
Yu Chen, Wei Zhu, Shu Fan, Yan Fan, Ning Yang, Tao Wu, Le Ji, Wei Xie, Rengui Bade, Shuyuan Jiang, Xiaolei Liu, Guo Shao, Gang Wu, Xiaoe Jia
Abstract
Introduction: Rare-earth nanoparticles in the environment and human body pose a potential threat to human health. Although toxic effects of rare-earth nanoparticles have been extensively studied, the effects on the early development are not well understood. In this study, we attempted to explain the toxic effects of neodymium oxide (Nd 2 O 3 ) nanoparticles on early development. Methods: We added the Nd 2 O 3 nanoparticles at different concentrations and recorded the mortality and malformation rate per 24 hrs under a microscope. The live embryos treated with Nd 2 O 3 nanoparticles were imaged as movies and Z step lapses with a confocal microscope, and heart rates were counted for 30 s to measure the cardiac function. The live Tg ( Flk1 :EGFP) transgenic embryos exposed to Nd 2 O 3 nanoparticles were observed under confocal microscope to measure the cerebrovascular development. Subsequently, we extracted the total protein for Western blot at 5 days post-fertilisation (dpf). Embryos were collected to undergo TUNEL staining for apoptosis detection. Results: Nd 2 O 3 nanoparticles disturbed embryo development at high concentrations (> 200 μg/mL). The mortality and malformation rate gradually increased in a dose-dependent manner by morphological observation, while the Nd 2 O 3 median lethal concentration (LD50) was 203.4 μg/mL at 120 hrs post-fertilisation (hpf). Furthermore, the Nd 2 O 3 -treated embryos showed severe arrhythmia and reduced heart rate. We also observed the markedly cerebrovascular disappearance at middle concentration (100 and 200 μg/mL). The downregulated autophagy flux in brain blood vessels and increased apoptosis level in neurons might affect vessels sprouting and contribute to the vanished cerebrovascular. Conclusion: The results suggested that the embryos exposed to Nd 2 O 3 activated the apoptosis pathway and induced toxicity and abnormal cardiac/cerebrovascular development. Keywords: Nd 2 O 3 , zebrafish, toxicity, arrhythmias, cerebrovascular