International Journal of Nanomedicine (Jan 2020)
Nd2O3 Nanoparticles Induce Toxicity and Cardiac/Cerebrovascular Abnormality in Zebrafish Embryos via the Apoptosis Pathway
Abstract
Yu Chen, 1–3,* Wei Zhu, 4,* Fan Shu, 5 Yan Fan, 1, 2 Ning Yang, 1, 2 Tao Wu, 1, 2 Le Ji, 1, 2 Wei Xie, 1, 2 Rengui Bade, 1, 2 Shuyuan Jiang, 1, 2 Xiaolei Liu, 1, 2 Guo Shao, 1–3 Gang Wu, 1, 2 Xiaoe Jia 1–3 1Biomedicine Research Center, Neuroscience Institute, Baotou Medical College, Baotou 014040, People’s Republic of China; 2Inner Mongolia Key Laboratory of Hypoxic Translational Medicine, Baotou Medical College, Baotou 014040, People’s Republic of China; 3Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 4School of Pharmacy, Baotou Medical College, Baotou 014040, People’s Republic of China; 5Third Hospital of Baotou, Baotou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoe Jia Email [email protected] Wu Tel/Fax +86-472-7167830Email [email protected]: 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 2O 3) nanoparticles on early development.Methods: We added the Nd 2O 3 nanoparticles at different concentrations and recorded the mortality and malformation rate per 24 hrs under a microscope. The live embryos treated with Nd 2O 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 2O 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 2O 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 2O 3 median lethal concentration (LD50) was 203.4 μg/mL at 120 hrs post-fertilisation (hpf). Furthermore, the Nd 2O 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 2O 3 activated the apoptosis pathway and induced toxicity and abnormal cardiac/cerebrovascular development.Keywords: Nd 2O 3, zebrafish, toxicity, arrhythmias, cerebrovascular
