Liu Han, Nie Fang-Hong, Lin Hong-Ying, Ma Yi, Ju Xiang-Hong, Chen Jin-Jun, Gooneratne Ravi
Department of Veterinary Medicine, Agricultural College, Guangdong Ocean University, Zhanjiang, 524088, China.
College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, 524088, China.
Environ Toxicol. 2016 Mar;31(3):295-303. doi: 10.1002/tox.22044. Epub 2014 Sep 12.
3,3',4,4',5-Pentachlorobiphenyl (PCB126) cause multiple adverse effects in organisms including animals and humans. Although PCB toxicities are linked to oxidative damage in rodents, the mechanism in early life stages of zebrafish is not clear. To explore the developmental toxicity mechanism of PCB126, three paradigms (toxicological phenotypes, biochemical changes, and molecular changes) were studied in 3-h postfertilization (hpf) zebrafish (Danio rerio) embryos exposed to different PCB126 concentrations (0, 16, 32, 64, and 128 μg/L) until 168 hpf. Developmental malformations, including pericardial and yolk sac edema, impaired lower jaw growth, spinal curvature, head edema and failure to inflate the swim bladder were observed, some as early as 72 hpf. Mortality was not apparent in early stages but significantly increased in a dose-dependent manner from 144 hpf onward. A dose-dependent significant increase in malformation rate was observed from 72 hpf onward with up to 100% at 132 hpf in embryos exposed to 128 μg/L of PCB126. Higher doses of PCB126 significantly decreased the copper-zinc superoxide dismutase (CuZn-Sod), catalase (Cat), and glutathione peroxidase (Gpx) enzyme activities at 96, 132 hpf, but markedly declined from thereafter. PCB126 at 128 μg/L significantly increased the malondialdehyde content at 72, 96, and 132 hpf. The transcriptional gene expression of antioxidant enzymes Cat and Gpx was upregulated in embryos exposed to 64 μg/L of PCB126 at 24 and 96 hpf. Sod1 messenger RNA (mRNA) was low in embryos exposed to 32 μg/L at 72 and 96 hpf but was induced in embryos exposed to 64 and 128 μg/L doses at 132 hpf. Collectively, the results suggest oxidative stress as a major factor in the induction of multiple developmental abnormalities in early life stages of zebrafish exposed to PCB126. However, the relationship between the antioxidant enzyme activity and the mRNA expression was not clear and the potential reasons for this are discussed.
3,3',4,4',5-五氯联苯（PCB126）会对包括动物和人类在内的生物体产生多种不良影响。尽管多氯联苯的毒性与啮齿动物的氧化损伤有关，但斑马鱼早期生命阶段的机制尚不清楚。为了探究PCB126的发育毒性机制，我们对受精后3小时（hpf）的斑马鱼（Danio rerio）胚胎进行了研究，这些胚胎暴露于不同浓度（0、16、32、64和128μg/L）的PCB126中，直至168 hpf，研究了三种范式（毒理学表型、生化变化和分子变化）。观察到发育畸形，包括心包和卵黄囊水肿、下颌生长受损、脊柱弯曲、头部水肿和鳔充气失败，有些畸形最早在72 hpf时就出现了。早期死亡率不明显，但从144 hpf开始以剂量依赖的方式显著增加。从72 hpf开始观察到畸形率呈剂量依赖性显著增加，暴露于128μg/L PCB126的胚胎在132 hpf时畸形率高达100%。较高剂量的PCB126在96、132 hpf时显著降低了铜锌超氧化物歧化酶（CuZn-Sod）、过氧化氢酶（Cat）和谷胱甘肽过氧化物酶（Gpx）的酶活性，但此后显著下降。128μg/L的PCB126在72、96和132 hpf时显著增加了丙二醛含量。在24和96 hpf时，暴露于64μg/L PCB126的胚胎中抗氧化酶Cat和Gpx的转录基因表达上调。在72和96 hpf时，暴露于32μg/L的胚胎中Sod1信使核糖核酸（mRNA）水平较低，但在132 hpf时，暴露于64和128μg/L剂量的胚胎中Sod1 mRNA被诱导。总体而言，结果表明氧化应激是暴露于PCB126的斑马鱼早期生命阶段诱导多种发育异常的主要因素。然而，抗氧化酶活性与mRNA表达之间的关系尚不清楚，并对此潜在原因进行了讨论。
