SCIENCE OF THE TOTAL ENVIRONMENT
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2018
·
IF 4.61
Mengmeng Huang,Fanghuan Zhu,Jingjing Jiao,Jun Wang,Yu Zhang
Acrylamide (AA), a ubiquitous chemical that is present in surrounding environment and baked or fried carbohydrate-rich food, has recently been linked to cardiac developmental toxicity. However, the toxicological role of AA exposure in the cardiac development remains largely unknown. Here we showed the cardiotoxicity of AA and its role in cardiomyocyte interactions in zebrafish embryos during ventricular morphogenesis. Using the embryo model of transgenic zebrafish Tg(Tp1:d2GFP ; myl7:mCherry) , we found AA interfered the dynamics of Notch signaling in the endocardium during early cardiogenesis. Prolonged exposure to AA thickened the chamber wall and prevented the trabeculae from extending into the lumen of ventricular chamber. As a result, AA reduced the ventricular shortening fraction and spatial dimension via excessively activating the Notch signal in myocardium during cardiac maturation. Moreover, exposure to AA inhibited the re-distribution of N ‑cadherin and failed to coordinate cardiomyocyte interactions between the myocardium layers due to the lack of delaminated cardiomyocytes. Therefore, AA-treated embryos exhibited subcellular pathological states including disarrayed myofibrils and abnormal morphology of mitochondria despite normal proliferation of cardiomyocytes. In addition, we found overexpression of some cardiac-specific transcription factors, such as hand2 and nkx2.5 , in hearts of AA-treated embryos compared with those in control group. Our study provided the evidence that the period of ventricular chamber morphogenesis might be a vulnerable window in zebrafish, and revealed new insights into how AA might exert cardiac developmental toxicity.
研究领域:
毒理学
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发育生物学
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心脏病学
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DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
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2015
·Vol. 35
·期 12
·1473-1480
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IF 2.982
Bing Shen,Hong-Cui Liu,Wen-Bin Ou,Grant Eilers,Sheng-Mei Zhou,Fan-Guo Meng,Chun-Qi Li,Yong-Quan Li
Basic Violet 14, Direct Red 28 and Acid Red 26 are classified as carcinogenic dyes in the European textile ecology standard, despite insufficient toxicity data. In this study, the toxicity of these dyes was assessed in a zebrafish model, and the underlying toxic mechanisms were investigated. Basic Violet 14 and Direct Red 28 showed acute toxicity with a LC 50 value at 60.63 and 476.84 µg ml –1 , respectively, whereas the LC 50 of Acid Red 26 was between 2500 and 2800 µg ml –1 . Treatment with Basic Violet 14, Direct Red 28 and Acid Red 26 resulted in common developmental abnormalities including delayed yolk sac absorption and swimming bladder deflation. Hepatotoxicity was observed in zebrafish treated with Basic Violet 14, and cardiovascular toxicity was found in zebrafish treated with Acid Red 26 at concentrations higher than 2500 µg ml –1 . Basic Violet 14 also caused significant up-regulation of GCLC gene expression in a dose-dependent manner whereas Acid Red 26 induced significant up-regulation of NKX2.5 and down-regulation of GATA4 at a high concentration in a dose-dependent manner. These results suggest that Basic Violet 14, Direct Red 28 and Acid Red 26 induce developmental and organ-specific toxicity, and oxidative stress may play a role in the hepatotoxicity of Basic Violet 14, the suppressed GATA4 expression may have a relation to the cardiovascular toxicity of Acid Red 26. Copyright © 2015 John Wiley & Sons, Ltd.
研究领域:
毒理学
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分子生物学
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发育生物学
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环境科学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Xin Wang,Fan Chen,Jian Lu,Mengqi Wu,Jiagao Cheng,Wenping Xu,Zhong Li,Yang Zhang
Acetochlor (ACT) is a widely used pesticide, yet the environmental and health safety of its chiral isomers remains inadequately evaluated. In this study, we evaluated the toxicity of ACT and its chiral isomers in a zebrafish model. Our findings demonstrate that ACT and its chiral isomers disrupt early zebrafish embryo development, inducing oxidative stress, abnormal lipid metabolism, and apoptosis. Additionally, ACT and its chiral isomers lead to cardiovascular damage, including reduced heart rate, decreased red blood cell (RBC) flow rate, and vascular damage. We further observed that (+)- S -ACT has a significant impact on the transcription of genes involved in cardiac and vascular development, including tbx5 , hand2 , nkx2.5 , gata4 , vegfa , dll4 , cdh5 , and vegfc . Our study highlights the potential risk posed by different conformations of chiral isomeric pesticides and raises concerns regarding their impact on human health. Overall, our results suggest that the chiral isomers of ACT induce developmental defects and cardiovascular toxicity in zebrafish, with (+)- S -ACT being considerably more toxic to zebrafish than (−)- R -ACT.
研究领域:
环境毒理学
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发育生物学
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心血管科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）