Jaeschke Hartmut, Ramachandran Anup
Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Curr Opin Toxicol. 2020 Apr-Jun;20-21:9-14. doi: 10.1016/j.cotox.2020.03.003. Epub 2020 Mar 25.
Acetaminophen is a widely used analgesic and antipyretic, which can cause liver injury after an overdose. Although a controversial topic for some time, solid evidence for a critical role of oxidative and nitrosative stress has emerged during the last two decades. This review will discuss the cellular sources, amplification mechanisms and the consequences of the excessive formation of reactive oxygen and nitrogen species in the clinically relevant mouse model of acetaminophen hepatotoxicity. This new mechanistic insight contributes to the better understanding of the mechanism of action of N-acetylcysteine, the only clinically approved antidote. In addition, it provides the rationale for the development of new antidotes that target the formation or metabolism of mitochondrial superoxide.
对乙酰氨基酚是一种广泛使用的解热镇痛药，过量服用后可导致肝损伤。尽管这一话题在一段时间内存在争议，但在过去二十年中，氧化应激和亚硝化应激起关键作用的确凿证据已经出现。本综述将讨论在对乙酰氨基酚肝毒性的临床相关小鼠模型中，活性氧和活性氮过量生成的细胞来源、放大机制及其后果。这种新的机制性见解有助于更好地理解N-乙酰半胱氨酸（唯一临床批准的解毒剂）的作用机制。此外，它还为开发针对线粒体超氧化物形成或代谢的新型解毒剂提供了理论依据。
