In Vitro Cell-Based Models of Drug-Induced Hepatotoxicity Screening: Progress and Limitation Publisher Pubmed



Mirahmad M¹ ; Sabourian R² ; Mahdavi M¹ ; Larijani B¹ ; Safavi M³
Source: Drug Metabolism Reviews Published:2022

Abstract

Drug-induced liver injury (DILI) is one of the major causes of post-approval withdrawal of therapeutics. As a result, there is an increasing need for accurate predictive in vitro assays that reliably detect hepatotoxic drug candidates while reducing drug discovery time, costs, and the number of animal experiments. In vitro hepatocyte-based research has led to an improved comprehension of the underlying mechanisms of chemical toxicity and can assist the prioritization of therapeutic choices with low hepatotoxicity risk. Therefore, several in vitro systems have been generated over the last few decades. This review aims to comprehensively present the development and validation of two-dimensional (2D) and three-dimensional (3D) culture approaches on hepatotoxicity screening of compounds and highlight the main factors affecting predictive power of experiments. To this end, we first summarize some of the recognized hepatotoxicity mechanisms and related assays used to appraise DILI mechanisms and then discuss the challenges and limitations of in vitro models. © 2022 Informa UK Limited, trading as Taylor & Francis Group.