Hexabromocyclododecane-induced developmental toxicity and apoptosis in zebrafish embryos.
Hexabromocyclododecane (HBCD) is widely used as a brominated flame retardant, and has been detected in the aquatic environment, wild animals, and humans. However, details of the environmental health risk of HBCD are not well known. In this study, zebrafish embryos were used to assess the developmental toxicity of the chemical. Four-hour post-fertilization (hpf) zebrafish embryos were exposed to various concentrations of HBCD (0, 0.05, 0.1, 0.5, and 1.0 mg L(-1)) until 96 h. Exposure to 0.1, 0.5, and 1.0 mg L(-1) HBCD significantly increased the malformation rate and reduced survival in the 0.5 and 1.0 mg L(-1) HBCD exposure groups. Acridine orange (AO) staining showed that HBCD exposure resulted in cell apoptosis. Reactive oxygen species (ROS) was significantly induced at exposures of 0.1, 0.5, and 1.0 mg L(-1) HBCD. To test the apoptotic pathway, several genes related to cell apoptosis, such as p53, Puma, Apaf-1, caspase-9, and caspase-3, were examined using real-time PCR. The expression patterns of these genes were up-regulated to some extent. Two anti-apoptotic genes, Mdm2 (antagonist of p53) and Bcl-2 (inhibitor of Bax), were down-regulated, and the activity of capspase-9 and caspase-3 was significantly increased. The overall results demonstrate that waterborne HBCD is able to produce oxidative stress and induce apoptosis through the involvement of caspases in zebrafish embryos. The results also indicate that zebrafish embryos can serve as a reliable model for the developmental toxicity of HBCD.
Deng
Jun
J
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Donghu South Road 7, Wuhan 430072, China.
Yu
Liqin
L
Liu
Chunsheng
C
Yu
Ke
K
Shi
Xiongjie
X
Yeung
Leo W Y
LW
Lam
Paul K S
PK
Wu
Rudolf S S
RS
Zhou
Bingsheng
B
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000187:drug effects; D005260:Female; D005411:Flame Retardants / Q000633:toxicity*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D005411:Flame Retardants; D006842:Hydrocarbons, Brominated; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C089796:hexabromocyclododecane