Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, Ji'an, Jiangxi, China; Center for Developmental Biology of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an, Jiangxi, China.
Department of Ultrasound, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, 330006, China.
Aquat Toxicol. 2019 May;210:242-250. doi: 10.1016/j.aquatox.2019.02.020. Epub 2019 Feb 27.
Oxine-copper (OxCu) is generally used as an agricultural pesticide and induces harmful effects on ecosystems. In this study, zebrafish was used to assess the aquatic toxicity of OxCu. To detect the effects on development, embryos of 6 h post-fertilization (hpf) were exposed to 10 μg/L, 20 μg/L, 40 μg/L OxCu for 18 h; meanwhile, to evaluate the effects on the behavior, larval fish at 6 days post-fertilization (dpf) were exposed to the same concentrations for 24 h. Here, we show that there are embryonic developmental defects, including abnormalities of head and trunk, brain ventricle atrophy, reduced newborn neurons, disordered neurons, increased intercellular space, concentrated cytoplasm, decreased heart beat and blood flow velocity, and developmental delay of the vascular system; in addition, some embryos exposed to the high concentration of OxCu degraded from the tail. We also found that the spontaneous tail coiling frequency and AChE enzyme activity were reduced, while oxidative stress (free radical damage) and cell apoptosis were significantly increased. Moreover, the expression of genes involved in neurodevelopment, vascular development and apoptosis were dysregulated in the OxCu exposed embryos in a concentration-dependent manner. Finally, we found that after exposure to OxCu, larval locomotor activity was decreased and accompanied by Parkinson-like (increased absolute turn angle and sinuosity) and anxiety-like (preferred to the central area) behavior. These results indicate that OxCu induces developmental toxicity and behavioral alterations by affecting AChE enzyme activity and oxidative stress. Our data present new proofs of OxCu toxicity and a warning for its application.
氧肟酸铜（OxCu）通常用作农业杀虫剂，对生态系统有有害影响。在本研究中，使用斑马鱼评估 OxCu 的水生毒性。为了检测对发育的影响，将受精后 6 小时（hpf）的胚胎暴露于 10μg/L、20μg/L、40μg/L OxCu 中 18 小时；同时，为了评估对行为的影响，受精后 6 天（dpf）的幼鱼暴露于相同浓度下 24 小时。在这里，我们表明存在胚胎发育缺陷，包括头部和躯干的异常、脑室内萎缩、新生神经元减少、神经元排列紊乱、细胞间隙增大、细胞质浓缩、心跳和血流速度减慢以及血管系统发育延迟；此外，一些暴露于高浓度 OxCu 的胚胎从尾部降解。我们还发现自发的尾巴卷曲频率和乙酰胆碱酯酶（AChE）活性降低，而氧化应激（自由基损伤）和细胞凋亡显著增加。此外，OxCu 暴露的胚胎中，与神经发育、血管发育和细胞凋亡相关的基因表达呈浓度依赖性失调。最后，我们发现暴露于 OxCu 后，幼鱼的运动活性降低，伴有帕金森样（绝对转弯角度和弯曲度增加）和焦虑样（偏好中心区域）行为。这些结果表明，OxCu 通过影响 AChE 酶活性和氧化应激引起发育毒性和行为改变。我们的数据提供了 OxCu 毒性的新证据，并对其应用提出了警告。
