Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Drug Metab Rev. 2022 May;54(2):161-193. doi: 10.1080/03602532.2022.2064487. Epub 2022 Apr 22.
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 assays that reliably detect hepatotoxic drug candidates while reducing drug discovery time, costs, and the number of animal experiments. 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 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 models.
药物性肝损伤（DILI）是批准后治疗药物撤回的主要原因之一。因此，人们越来越需要准确的预测性检测方法，以便在降低药物发现时间、成本和动物实验数量的同时，可靠地检测出具有肝毒性的候选药物。基于肝细胞的研究提高了对化学毒性潜在机制的理解，并有助于优先选择低肝毒性风险的治疗选择。因此，在过去几十年中已经开发出了几种系统。本综述旨在全面介绍化合物肝毒性筛选的二维（2D）和三维（3D）培养方法的发展和验证，并强调影响实验预测能力的主要因素。为此，我们首先总结了一些已被认可的肝毒性机制和相关检测方法，用于评估 DILI 机制，然后讨论了模型的挑战和局限性。
