College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.
Aquat Toxicol. 2018 May;198:215-223. doi: 10.1016/j.aquatox.2018.03.012. Epub 2018 Mar 13.
Tris (2-butoxyethyl) phosphate (TBOEP) is an environmental contaminant that poses serious risks to aquatic organisms and their associated ecosystem. Recently, the reproductive and developmental toxicology of TBOEP has been reported. However, fewer studies have assessed the neurotoxic effects in zebrafish (Danio rerio) larvae. In this study, zebrafish embryos were subjected to waterborne exposure of TBOEP at 0, 50, 500, 1500 and 2500 μg/L from 2 to 144-h post-fertilization (hpf). Behavioral measurements showed that TBOEP exposure reduced embryonic spontaneous movement and decreased swimming speed of larvae in response to dark stimulation. In accordance with these motor effects, TBOEP treatment reduced neuron-specific GFP expression in transgenic Tg (HuC-GFP) zebrafish larvae and inhibited the growth of secondary motoneurons, as well as decreased expression of marker genes related to central nervous system development in TBOEP treated group. Furthermore, increased concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as reduction of SOD activity were detected in TBOEP exposure group. The present results showed that the alteration in motor neuron and oxidative stress could together lead to the motor behavior alterations induced by TBOEP.
三（2-丁氧基乙基）磷酸酯（TBOEP）是一种环境污染物，对水生生物及其相关生态系统构成严重威胁。最近，已有关于 TBOEP 的生殖和发育毒理学的报道。然而，较少有研究评估 TBOEP 对斑马鱼（Danio rerio）幼鱼的神经毒性作用。在这项研究中，从受精后 2 至 144 小时（hpf），将斑马鱼胚胎暴露于 0、50、500、1500 和 2500μg/L 的 TBOEP 水相中。行为测量显示，TBOEP 暴露减少了胚胎的自发运动，并降低了对黑暗刺激的幼鱼游泳速度。与这些运动效应一致，TBOEP 处理降低了转基因 Tg（HuC-GFP）斑马鱼幼鱼中神经元特异性 GFP 的表达，并抑制了次级运动神经元的生长，以及减少了 TBOEP 处理组中与中枢神经系统发育相关的标记基因的表达。此外，在 TBOEP 暴露组中检测到活性氧（ROS）和丙二醛（MDA）浓度增加，以及 SOD 活性降低。本研究结果表明，运动神经元的改变和氧化应激可能共同导致 TBOEP 引起的运动行为改变。
