Unidad de Hepatología Experimental, Torre A, Instituto Investigación Sanitaria La Fe (IIS La Fe), Av Fernando Abril Martorell 106, 46026, Valencia, Spain,
Arch Toxicol. 2015 Jul;89(7):1007-22. doi: 10.1007/s00204-015-1503-z. Epub 2015 Mar 19.
High-content screening is the application of automated microscopy and image analysis to both cell biology and drug discovery. Over the last decade, this technique has emerged as a useful technology that allows the simultaneous measurement of different parameters at a single-cell level. Hepatotoxicity is a compelling reason for drug nonapprovals and withdrawals. It is recognized that the safety of a compound cannot be based on a single in vitro assay, and existing methods are not predictive of drug-induced toxicity. However, different HCS assays have been recently demonstrated as being powerful for identifying different mechanisms implicated in drug-induced toxicity with high sensitivity and specificity. These assays integrate the data obtained from different cell function indicators and can be easily incorporated into basic screening processes for the safety evaluation and selection of drug candidates; thus, they contribute greatly to lessen the likelihood of drug failure. Exploring the use of cellular imaging technology in drug-induced liver injury by reviewing the different tests proposed provides evidence that this technology has a strong impact on drug discovery.
高内涵筛选是自动化显微镜和图像分析在细胞生物学和药物发现中的应用。在过去的十年中，这项技术已经成为一种有用的技术，可以在单细胞水平上同时测量不同的参数。肝毒性是药物不批准和撤回的一个重要原因。人们认识到，化合物的安全性不能仅基于单一的体外测定，而且现有的方法不能预测药物引起的毒性。然而，最近已经证明，不同的 HCS 测定方法具有很高的灵敏度和特异性，可用于识别药物诱导毒性中涉及的不同机制。这些测定方法整合了来自不同细胞功能指标的数据，可以很容易地纳入药物候选物安全性评估和选择的基本筛选过程中；因此，它们大大降低了药物失败的可能性。通过回顾提出的不同测试，探讨细胞成像技术在药物性肝损伤中的应用，为该技术对药物发现具有强大的影响力提供了证据。
