Zhu Biran, Wang Qiangwei, Shi Xiongjie, Guo Yongyong, Xu Tao, Zhou Bingsheng
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 100049, China.
College of Life Sciences, Wuhan University, Wuhan 430072, China.
Chemosphere. 2016 Feb;144:1646-54. doi: 10.1016/j.chemosphere.2015.10.056. Epub 2015 Oct 28.
The effect of combined exposure to decabromodiphenyl ether (BDE-209) and lead (Pb) on neurodevelopment of zebrafish (Danio rerio) larvae was investigated. Zebrafish embryos were exposed to Pb (0, 5, 10, 20 µg/L) and BDE-209 (0, 50, 100, 200 µg/L), either alone or in combination (Mix1: 5 + 50 µg/L, Mix2: 10 + 100 µg/L, Mix3: 20 + 200 µg/L) for up to 144 h post-fertilization. Growth of secondary motoneuron axons and expression of genes related to central nervous system development was significantly inhibited in Mix3 co-exposure group. A significant increase in reactive oxygen species (ROS), lipid peroxidation, DNA damage, and perturbation of the antioxidant system was detected in the Mix3 group compared to single-toxicant treatments or control. Depressed locomotor activity was recorded in the Mix2 and Mix3 groups. Addition of N-acetyl cysteine to Mix3 eliminated excessive ROS, and protected against lipid peroxidation, DNA damage, and locomotor dysfunction. Pb uptake was increased in the presence of BDE-209, but BDE-209 bioconcentration and the ability to metabolize BDE-209 were decreased in the presence of Pb. These results suggest that BDE-209 and Pb have a synergistic disruptive effect on neurodevelopment in zebrafish larvae by enhanced generation of ROS, which is a major factor that contributes to developmental neurotoxicity.
研究了十溴二苯醚（BDE - 209）和铅（Pb）联合暴露对斑马鱼（Danio rerio）幼体神经发育的影响。斑马鱼胚胎在受精后长达144小时内，分别单独或联合暴露于Pb（0、5、10、20 µg/L）和BDE - 209（0、50、100、200 µg/L）中（混合物1：5 + 50 µg/L，混合物2：10 + 100 µg/L，混合物3：20 + 200 µg/L）。混合物3联合暴露组中，次级运动神经元轴突的生长以及与中枢神经系统发育相关基因的表达受到显著抑制。与单一毒物处理组或对照组相比，混合物3组中活性氧（ROS）显著增加、脂质过氧化、DNA损伤以及抗氧化系统紊乱。混合物2组和混合物3组记录到运动活性降低。向混合物3中添加N - 乙酰半胱氨酸可消除过量的ROS，并防止脂质过氧化、DNA损伤和运动功能障碍。在BDE - 209存在的情况下，Pb的吸收增加，但在Pb存在的情况下，BDE - 209的生物富集以及代谢BDE - 209的能力降低。这些结果表明，BDE - 209和Pb通过增强ROS的生成对斑马鱼幼体的神经发育具有协同破坏作用，而ROS是导致发育性神经毒性的主要因素。
