Alpha-GST Release as a Predictive Marker of Drug Induced Hepatotoxicity in 3D InSight™ Liver Microtissues

In this study, the assay of alpha-GST release, utilizing the EKF Diagnostics alpha-GST ELISA kits, and the Promega CellTiter-Glo® Luminescent Cell ATP assay were compared as tests for hepatotoxicity using InSphero’s 3D InSight™ Liver Microtissues. As test substances, two compounds with known hepatotoxic risks were chosen: Amiodarone and Diclofenac. Drug induced liver injury (DILI) is a major obstacle in the development of new pharmaceutical identities. Evaluation of potential DILI effects of novel compounds during pre-clinical phases is, therefore, a prerequisite for their safe entry into clinical trials. Hepatocytes, the major cell type in the liver, contain high amounts of metabolic enzymes, which are released upon cellular injury into the cell culture supernatant. Beside the commonly used markers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alpha-GST is increasingly being used as a liver injury marker.