A Multi‐Parametric Fluorescent Assay for the Screening and Mechanistic Study of Drug‐Induced Steatosis in Liver Cells in Culture

Abstract

Human hepatic cells have been used for drug safety risk evaluations throughout early development phases. They provide rapid, cost-effective early feedback to identify drug candidates with potential hepatotoxicity. This unit presents a cell-based assay to evaluate the risk of liver damage associated with steatogenic drugs. Detailed protocols for cell exposure to test compounds and for the assessment of steatosis-related cell parameters (intracellular lipid content, reactive oxygen species production, mitochondrial impairment, and cell death) are provided. A few representative results that illustrate the utility of this procedure for the screening of drug-induced steatosis are shown. © 2017 by John Wiley & Sons, Inc.

Application of high-throughput transcriptomics for mechanism-based biological read-across of short-chain carboxylic acid analogues of valproic acid

“…This protocol describes an in vitro assay for the detection of drug-induced steatosis and the mechanisms implicated using high-content imaging. The protocol is based on the measurement of different endpoints that are indicative of hepatotoxicity and specifically steatosis by means of high-content imaging and it has been previously used and published in the context of drug-induced hepatotoxicity ( Donato et al, 2012;Tolosa et al, 2015a;Tolosa et al, 2015b;Tolosa et al, 2017;Tolosa et al, 2016;Tolosa et al, 2013;Tolosa et al, 2012))…”