Dept. of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Dept. of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Dept. of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA.
Biochim Biophys Acta Mol Basis Dis. 2019 May 1;1865(5):1031-1039. doi: 10.1016/j.bbadis.2018.08.037. Epub 2018 Sep 3.
Drug-induced liver injury (DILI) presents unique challenges for consumers, clinicians, and regulators. It is the most common cause of acute liver failure in the US. It is also one of the most common reasons for termination of new drugs during pre-clinical testing and withdrawal of new drugs post-marketing. DILI is generally divided into two forms: intrinsic and idiosyncratic. Many of the challenges with DILI are due in large part to poor understanding of the mechanisms of toxicity. Although useful models of intrinsic DILI are available, they are frequently misused. Modeling idiosyncratic DILI presents greater challenges, but promising new models have recently been developed. The purpose of this manuscript is to provide a critical review of the most popular animal models of DILI, and to discuss the future of DILI research.
药物性肝损伤 (DILI) 给消费者、临床医生和监管机构带来了独特的挑战。它是美国急性肝衰竭的最常见原因。它也是临床前测试中终止新药和上市后撤回新药的最常见原因之一。DILI 一般分为两种形式：内在型和特发性。DILI 的许多挑战在很大程度上是由于对毒性机制的理解不佳。虽然有可用的内在型 DILI 有用模型，但它们经常被误用。特发性 DILI 的建模提出了更大的挑战，但最近已经开发出有前途的新模型。本文的目的是对最流行的 DILI 动物模型进行批判性评价，并讨论 DILI 研究的未来。
