He Jian-Hui, Guo Sheng-Ya, Zhu Feng, Zhu Jun-Jing, Chen Yun-Xiang, Huang Chang-Jiang, Gao Ji-Min, Dong Qiao-Xiang, Xuan Yao-Xian, Li Chun-Qi
Hunter Biotechnology, Inc., Transfarland, Hangzhou, Zhejiang Province 311231, PR China.
J Pharmacol Toxicol Methods. 2013 Jan-Feb;67(1):25-32. doi: 10.1016/j.vascn.2012.10.003. Epub 2012 Nov 3.
Numerous studies have confirmed that zebrafish and mammalian toxicity profiles are strikingly similar and the transparency of larval zebrafish permits direct in vivo assessment of drug toxicity including hepatotoxicity in zebrafish.
Hepatotoxicity of 6 known mammalian hepatotoxic drugs (acetaminophen [APAP], aspirin, tetracycline HCl, sodium valproate, cyclophosphamide and erythromycin) and 2 non-hepatotoxic compounds (sucrose and biotin) were quantitatively assessed in larval zebrafish using three specific phenotypic endpoints of hepatotoxicity: liver degeneration, changes in liver size and yolk sac retention. Zebrafish liver degeneration was originally screened visually, quantified using an image-based morphometric analysis and confirmed by histopathology.
All the tested mammalian hepatotoxic drugs induced liver degeneration, reduced liver size and delayed yolk sac absorption in larval zebrafish, whereas the non-hepatotoxic compounds did not have observable adverse effect on zebrafish liver. The overall prediction success rate for hepatotoxic drugs and non-hepatotoxic compounds in zebrafish was 100% (8/8) as compared with mammalian results, suggesting that hepatotoxic drugs in mammals also caused similar hepatotoxicity in zebrafish.
Larval zebrafish phenotypic assay is a highly predictive animal model for rapidly in vivo assessment of compound hepatotoxicity. This convenient, reproducible animal model saves time and money for drug discovery and can serve as an intermediate step between cell-based evaluation and conventional animal testing of hepatotoxicity.
大量研究证实，斑马鱼和哺乳动物的毒性特征极为相似，且斑马鱼幼体的透明性使得能够直接在体内评估药物毒性，包括斑马鱼的肝毒性。
使用肝毒性的三个特定表型终点：肝脏变性、肝脏大小变化和卵黄囊滞留，对6种已知的哺乳动物肝毒性药物（对乙酰氨基酚[APAP]、阿司匹林、盐酸四环素、丙戊酸钠、环磷酰胺和红霉素）和2种非肝毒性化合物（蔗糖和生物素）在斑马鱼幼体中的肝毒性进行了定量评估。斑马鱼肝脏变性最初通过肉眼筛选，使用基于图像的形态计量分析进行量化，并通过组织病理学进行确认。
所有测试的哺乳动物肝毒性药物均诱导斑马鱼幼体肝脏变性、肝脏大小减小和卵黄囊吸收延迟，而非肝毒性化合物对斑马鱼肝脏没有可观察到的不良影响。与哺乳动物结果相比，斑马鱼中肝毒性药物和非肝毒性化合物的总体预测成功率为100%（8/8），这表明哺乳动物中的肝毒性药物在斑马鱼中也会引起类似的肝毒性。
斑马鱼幼体表型分析是一种高度预测性的动物模型，可用于快速在体内评估化合物的肝毒性。这种方便、可重复的动物模型为药物发现节省了时间和金钱，并且可以作为基于细胞的肝毒性评估和传统动物测试之间的中间步骤。
