Laboratory for Molecular Biology and Genetic Engineering, Université de Liège, GIGA-R B34, Sart Tilman, 4000 Liège, Belgium.
Reprod Toxicol. 2012 Dec;34(4):568-83. doi: 10.1016/j.reprotox.2012.07.010. Epub 2012 Sep 13.
Standard toxicological assays using the zebrafish model system evaluate lethality and teratogenicity upon exposure during the first 2 days after fertilization. We tested the biological effects of several widely used drugs on zebrafish by acute treatment for 24 h starting at late embryonic stages, between 48 and 72 h post-fertilization. For 4 out of 6 compounds, we observed a higher sensitivity of late stage zebrafish embryos for general toxicity (lethality) compared to younger embryos. Morphological defects such as edema, body curvature, delayed growth, decreased heart rate and locomotion were observed for each of the compounds tested, often at sublethal concentrations. Gene expression studies on a set of four selected genes revealed a specific regulatory pattern for the different compounds tested. Our results allow us to compare various toxicological endpoints and may contribute to the design of a rational high throughput approach using the zebrafish model.
采用斑马鱼模型系统的标准毒理学检测，评估在受精后 2 天内暴露时的致死性和致畸性。我们通过在胚胎晚期（受精后 48 至 72 小时）开始的 24 小时急性处理，测试了几种广泛使用的药物对斑马鱼的生物学效应。对于 6 种化合物中的 4 种，我们观察到晚期斑马鱼胚胎对一般毒性（致死性）的敏感性高于早期胚胎。对于测试的每种化合物，均观察到形态缺陷，如水肿、身体弯曲、生长迟缓、心率和运动能力下降，这些缺陷通常在亚致死浓度下出现。对一组 4 个选定基因的基因表达研究揭示了不同测试化合物的特定调节模式。我们的结果允许我们比较各种毒理学终点，并有助于设计使用斑马鱼模型的合理高通量方法。
