Characterization of acrylamide-induced oxidative stress and cardiovascular toxicity in zebrafish embryos
Characterization of acrylamide-induced oxidative stress and cardiovascular toxicity in zebrafish embryos
复制标题
斑马鱼胚胎中丙烯酰胺诱导的氧化应激和心血管毒性的表征
DOI：
10.1016/j.jhazmat.2018.01.016
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发表时间：
2018-04-05
影响因子：
13.6
通讯作者：
Zhang, Yu
中科院分区：
文献类型：
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作者：
Huang, Mengmeng;Jiao, Jingjing;Zhang, Yu
丙烯酰胺（AA）是工业应用中的高产量化学品，广泛存在于富含碳水化合物的烘焙或油炸食品中。在这项研究中，我们揭示了AA诱导发育毒性与氧化应激状态和心脏区域脂质分布紊乱有关。AA治疗引起心血管系统缺陷，伴有显著的心脏畸形和功能障碍。我们还发现AA通过降低心肌细胞的增殖能力而不是细胞凋亡来减少心肌细胞的数量。MF 20/S46免疫荧光检测显示，AA处理后分化心肌的心腔特异性特征保持良好，但心脏成环和气球样变出现异常。此外，AA处理干扰房室管的分化，这表现为房室边界标志物bmp 4，tbx 2b和notch 1b的表达紊乱，并进一步证实了心脏瓣膜前体标志物has 2，klf 2a和nfatc 1的异位表达通过整体原位杂交。因此，我们的研究提供了AA在心血管系统中的心脏发育毒性的证据，并且还提出了关于经胎盘暴露于高水平AA对胎儿的危害和孕妇暴露于高水平AA的风险的健康问题。
Acrylamide (AA) is a high production volume chemical in industrial applications and widely found in baked or fried carbohydrate-rich foods. In this study, we unravelled that AA induced developmental toxicity associated with oxidative stress status and disordered lipid distribution in heart region of developing zebrafish. Treatment with AA caused a deficient cardiovascular system with significant heart malformation and dysfunction. We also found that AA could reduce the number of cardiomyocytes through the reduced capacity of cardiomyocyte proliferation rather than cell apoptosis. The cardiac looping and ballooning appeared abnormal though cardiac chamber-specific identity in the differentiated myocardium was maintained well after AA treatment through MF20/S46 immunofluorescence assay. Furthermore, treatment with AA disturbed the differentiation of atrioventricular canal, which was demonstrated by the disordered expressions of the atrioventricular boundary markers bmp4, tbx2b and notch1b and further confirmed by the ectopic expressions of the cardiac valve precursor markers has2, klf2a and nfatc1 through whole-mount in situ hybridization. Thus, our studies provide the evidence of cardiac developmental toxicity of AA in the cardiovascular system, and also raised health concern about the harm of trans-placental exposure to high level of AA for foetuses and the risk of high exposure to AA for the pregnant women.