High-Content Screening for the Detection of Drug-Induced Oxidative Stress in Liver Cells

Abstract

Drug-induced liver injury (DILI) remains a major cause of drug development failure, post-marketing warnings and restriction of use. An improved understanding of the mechanisms underlying DILI is required for better drug design and development. Enhanced reactive oxygen species (ROS) levels may cause a wide spectrum of oxidative damage, which has been described as a major mechanism implicated in DILI. Several cell-based assays have been developed as in vitro tools for early safety risk assessments. Among them, high-content screening technology has been used for the identification of modes of action, the determination of the level of injury and the discovery of predictive biomarkers for the safety assessment of compounds. In this paper, we review the value of in vitro high-content screening studies and evaluate how to assess oxidative stress induced by drugs in hepatic cells, demonstrating the detection of pre-lethal mechanisms of DILI as a powerful tool in human toxicology.

Keywords

• oxidative stress
• mitochondria
• high-content screening
• cell models
• hepatotoxicity