Raldúa Demetrio, Piña Benjamin
IDAEA-CSIC, Environmental Chemistry , Jordi Girona 18, 08034 Barcelona , Spain +34 93400 6157 ; +34 93204 5904 ;
Expert Opin Drug Metab Toxicol. 2014 May;10(5):685-97. doi: 10.1517/17425255.2014.896339. Epub 2014 Mar 11.
Off-target effects represent one of the major concerns in the development of new pharmaceuticals, requiring large-scale animal toxicity testing. Faster, cheaper and more reliable assays based on zebrafish embryos (ZE) are being developed as major tools for assessing toxicity of chemicals during the drug-discovery process.
This paper reviews techniques aimed to the analysis of in vivo sublethal toxic effects of drugs on major physiological functions, including the cardiovascular, nervous, neuromuscular, gastrointestinal and thyroid systems among others. Particular emphasis is placed on high-throughput screening techniques (HTS), including robotics, imaging technologies and image-analysis software.
The analysis of off-target effects of candidate drugs requires systemic analyses, as they often involve the complete organism rather than specific, tissue- or cell-specific targets. The unique physical and physiological characteristics of ZE make this system an essential tool for drug discovery and toxicity assessment. Different HTS methodologies applicable to ZE allow the screening of large numbers of different chemicals for many diverse and relevant toxic endpoints.
脱靶效应是新药物研发中的主要问题之一，这需要进行大规模动物毒性试验。基于斑马鱼胚胎（ZE）的更快、更便宜且更可靠的检测方法正在被开发出来，作为药物发现过程中评估化学物质毒性的主要工具。
本文综述了旨在分析药物对主要生理功能（包括心血管、神经、神经肌肉、胃肠和甲状腺系统等）的体内亚致死毒性效应的技术。特别强调了高通量筛选技术（HTS），包括机器人技术、成像技术和图像分析软件。
对候选药物脱靶效应的分析需要进行系统分析，因为它们通常涉及整个生物体而非特定的组织或细胞特异性靶点。斑马鱼胚胎独特的物理和生理特征使该系统成为药物发现和毒性评估的重要工具。适用于斑马鱼胚胎的不同高通量筛选方法允许针对许多不同且相关的毒性终点筛选大量不同的化学物质。
