High-content screening technology for studying drug-induced hepatotoxicity in cell models

Autores de IIS La Fe

• 

  Laia Tolosa Pardo

  Autor

• María José Gómez-Lechón Moliner

  Autor

• María Teresa Donato Martín

  Autor

Grupos

• Hepatología experimental y Trasplante hepático

Abstract

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.

Keywords

• High-content screening; Hepatotoxicity; Drugs; Mechanisms