Jinhua Municipal Central Hospital, Jinhua 321000, China.
Ningbo Medical Center Lihuili Hospital, Ningbo 315040, China.
Exp Biol Med (Maywood). 2023 May;248(5):412-424. doi: 10.1177/15353702221147563. Epub 2023 Jan 20.
Acetaminophen (APAP), a widely used antipyretic and analgesic drug in clinics, is relatively safe at therapeutic doses; however, APAP overdose may lead to fatal acute liver injury. Currently, -acetylcysteine (NAC) is clinically used as the main antidote for APAP poisoning, but its therapeutic effect remains limited owing to rapid disease progression and the general diagnosis of advanced poisoning. As is well known, APAP-induced hepatotoxicity (AIH) is mainly caused by the toxic metabolite -acetyl--benzoquinone imine (NAPQI), and the toxic mechanisms of AIH are complicated. Several cellular processes are involved in the pathogenesis of AIH, including liver metabolism, mitochondrial oxidative stress and dysfunction, sterile inflammation, endoplasmic reticulum stress, autophagy, and microcirculation dysfunction. Mitochondrial oxidative stress and dysfunction are the major cellular events associated with APAP-induced liver injury. Many biomolecules involved in these biological processes are potential therapeutic targets for AIH. Therefore, there is an urgent need to comprehensively clarify the molecular mechanisms underlying AIH and to explore novel therapeutic strategies. This review summarizes the various cellular events involved in AIH and discusses their potential therapeutic targets, with the aim of providing new ideas for the treatment of AIH.
对乙酰氨基酚（APAP）是临床中广泛使用的解热镇痛药，在治疗剂量下相对安全；然而，APAP 过量可能导致致命的急性肝损伤。目前，-乙酰半胱氨酸（NAC）被临床用作 APAP 中毒的主要解毒剂，但由于疾病进展迅速和一般诊断为晚期中毒，其治疗效果仍然有限。众所周知，APAP 诱导的肝毒性（AIH）主要是由有毒代谢物 -乙酰--苯醌亚胺（NAPQI）引起的，AIH 的毒理机制很复杂。几个细胞过程参与了 AIH 的发病机制，包括肝脏代谢、线粒体氧化应激和功能障碍、无菌性炎症、内质网应激、自噬和微循环功能障碍。线粒体氧化应激和功能障碍是与 APAP 诱导的肝损伤相关的主要细胞事件。这些生物学过程中涉及的许多生物分子都是 AIH 的潜在治疗靶点。因此，迫切需要全面阐明 AIH 的分子机制，并探索新的治疗策略。本综述总结了 AIH 涉及的各种细胞事件，并讨论了它们的潜在治疗靶点，以期为 AIH 的治疗提供新的思路。
