title: Effect of combined exposure to lead and decabromodiphenyl ether on neurodevelopment of zebrafish larvae.
abstract: 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.
authors.affiliation: 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.
authors.forename: Biran
authors.initials: B
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Qiangwei
authors.initials: Q
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Xiongjie
authors.initials: X
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Puai Hospital, Huazhong University of Science and Technology, Wuhan 430033, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China. Electronic address: bszhou@ihb.ac.cn.
authors.forename: Bingsheng
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D007854:Lead / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*
chemical_list: D055768:Halogenated Diphenyl Ethers; D017382:Reactive Oxygen Species; D014874:Water Pollutants, Chemical; D007854:Lead; C010902:decabromobiphenyl ether
keywords: BDE-209; Co-exposure; Developmental neurotoxicity; Lead; ROS