Hinz Kaitlyn, Niu Mengwei, Ni Hong-Min, Ding Wen-Xing
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Livers. 2024 Sep;4(3):377-387. doi: 10.3390/livers4030027. Epub 2024 Aug 14.
Acetaminophen (APAP) overdose can induce hepatocyte necrosis and acute liver failure in experimental rodents and humans. APAP is mainly metabolized via hepatic cytochrome P450 enzymes to generate the highly reactive metabolite -acetyl--benzoquinone imine (NAPQI), which forms acetaminophen protein adducts (APAP-adducts) and damages mitochondria, triggering necrosis. APAP-adducts and damaged mitochondria can be selectively removed by autophagy. Increasing evidence implies that the activation of autophagy may be beneficial for APAP-induced liver injury (AILI). In this minireview, we briefly summarize recent progress on autophagy, in particular, the pharmacological targeting of SQSTM1/p62 and TFEB in AILI.
对乙酰氨基酚(APAP)过量服用可在实验啮齿动物和人类中诱发肝细胞坏死和急性肝衰竭。APAP主要通过肝细胞色素P450酶代谢,生成高反应性代谢产物N - 乙酰 - 对苯醌亚胺(NAPQI),其形成对乙酰氨基酚蛋白加合物(APAP - 加合物)并损害线粒体,引发坏死。APAP - 加合物和受损的线粒体可通过自噬被选择性清除。越来越多的证据表明,自噬的激活可能对APAP诱导的肝损伤(AILI)有益。在这篇小型综述中,我们简要总结了自噬方面的最新进展,特别是在AILI中对SQSTM1/p62和转录因子EB(TFEB)的药物靶向作用。