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急性氧化锌纳米颗粒暴露可诱导胚胎-幼鱼斑马鱼的发育毒性、氧化应激和 DNA 损伤。

Acute ZnO nanoparticles exposure induces developmental toxicity, oxidative stress and DNA damage in embryo-larval zebrafish.

机构信息

State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090, China.

出版信息

Aquat Toxicol. 2013 Jul 15;136-137:49-59. doi: 10.1016/j.aquatox.2013.03.019. Epub 2013 Apr 10.


DOI:10.1016/j.aquatox.2013.03.019
PMID:23643724
Abstract

Nano-scale zinc oxide (nano-ZnO) is widely used in various industrial and commercial applications. However, the available toxicological information was inadequate to assess the potential ecological risk of nano-ZnO to aquatic organisms and the publics. In this study, the developmental toxicity, oxidative stress and DNA damage of nano-ZnO embryos were investigated in the embryo-larval zebrafish, the toxicity of Zn(2+) releasing from nano-ZnO were also investigated to ascertain the relationship between the nano-ZnO and corresponding Zn(2+). Zebrafish embryos were exposed to 1, 5, 10, 20, 50, and 100mg/L nano-ZnO and 0.59, 2.15, 3.63, 4.07, 5.31, and 6.04 mg/L Zn(2+) for 144 h post-fertilisation (hpf), respectively. Up to 144 hpf, activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and malondialdehyde (MDA) contents, the genes related to oxidative damage, reactive oxygen species (ROS) generation and DNA damage in zebrafish embryos were measured. The nano-ZnO was found to exert a dose-dependent toxicity to zebrafish embryos and larvae, reducing the hatching rate and inducing malformation and the acute toxicity to zebrafish embryos was greater than that of the Zn(2+) solution. The generation of ROS was significantly increased at 50 and 100mg/L nano-ZnO. DNA damage of zebrafish embryo was evaluated by single-cell gel electrophoresis and was enhanced with increasing nano-ZnO concentration. Moreover, the transcriptional expression of mitochondrial inner membrane genes related to ROS production, such as Bcl-2, in response to oxidative damage, such as Nqo1, and related to antioxidant response element such as Gstp2 were significantly down-regulated in the nano-ZnO treatment groups. However, the nano-ZnO up-regulated the transcriptional expression of Ucp2-related to ROS production. In conclusion, nano-ZnO induces developmental toxicity, oxidative stress and DNA damage on zebrafish embryos and the dissolved Zn(2+) only partially contributed to the toxicity of nano-ZnO. The adverse effects of nano-ZnO may be the important mechanisms of its toxicity to zebrafish embryos.

摘要

纳米氧化锌(nano-ZnO)广泛应用于各种工业和商业应用中。然而,现有的毒理学信息不足以评估纳米 ZnO 对水生生物和公众的潜在生态风险。在这项研究中,研究了纳米 ZnO 对斑马鱼胚胎的发育毒性、氧化应激和 DNA 损伤,还研究了纳米 ZnO 释放的 Zn(2+)的毒性,以确定纳米 ZnO 与相应的 Zn(2+)之间的关系。斑马鱼胚胎分别暴露于 1、5、10、20、50 和 100mg/L 的纳米 ZnO 和 0.59、2.15、3.63、4.07、5.31 和 6.04mg/L 的 Zn(2+),受精后 144 小时(hpf)。在 144 hpf 时,测量了超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPx)的活性,以及丙二醛(MDA)含量、与氧化损伤、活性氧(ROS)生成和斑马鱼胚胎 DNA 损伤相关的基因。结果表明,纳米 ZnO 对斑马鱼胚胎和幼鱼具有剂量依赖性毒性,降低孵化率并诱导畸形,对斑马鱼胚胎的急性毒性大于 Zn(2+)溶液。在 50 和 100mg/L 的纳米 ZnO 下,ROS 的生成显著增加。通过单细胞凝胶电泳评估了斑马鱼胚胎的 DNA 损伤,并随着纳米 ZnO 浓度的增加而增强。此外,与 ROS 生成(如 Bcl-2)相关的线粒体内膜基因的转录表达,如 Nqo1,以及与抗氧化反应元件(如 Gstp2)相关的基因,在纳米 ZnO 处理组中显著下调。然而,纳米 ZnO 上调了与 ROS 生成相关的 Ucp2 的转录表达。总之,纳米 ZnO 对斑马鱼胚胎的发育毒性、氧化应激和 DNA 损伤,溶解的 Zn(2+)仅部分贡献了纳米 ZnO 的毒性。纳米 ZnO 对斑马鱼胚胎的不利影响可能是其毒性的重要机制。

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