Institute of Toxicology, Shandong University, 44 West Wenhua Road, Jinan, 250012, Shandong, People's Republic of China.
Arch Toxicol. 2018 Jul;92(7):2153-2161. doi: 10.1007/s00204-018-2237-5. Epub 2018 Jun 6.
Acetaminophen (APAP) is a widely used analgesic and antipyretic drug. APAP overdose can induce acute liver injury in humans, which is responsible for approximately 50% of total cases of acute liver failure in the United States and some European countries. Currently, the metabolism of APAP in the body has been extensively investigated; however, the exact mechanisms for APAP hepatotoxicity are not well understood. Recent studies have shown that mitochondrial dysfunction, oxidative stress and inflammatory responses play a critical role in the pathogenesis of APAP hepatotoxicity. Autophagy is a catabolic machinery aimed at recycling cellular components and damaged organelles in response to a variety of stimuli, such as nutrient deprivation and toxic stress. Increasing evidence supports that autophagy is involved in the pathophysiological process of APAP-induced liver injury. In this review, we summarized the changes of autophagy in the liver following APAP intoxication and discussed the role and its possible mechanisms of autophagy in APAP hepatotoxicity. Furthermore, this review highlights the crosstalk between mitophagy, oxidative stress and inflammation in APAP-induced liver injury and presents some possible molecular mechanisms by which activated autophagy protects against APAP-induced liver injury.
对乙酰氨基酚（APAP）是一种广泛使用的镇痛药和解热药。APAP 过量会导致人类急性肝损伤，这在美国和一些欧洲国家约占急性肝功能衰竭总病例的 50%。目前，已广泛研究了体内 APAP 的代谢；然而，APAP 肝毒性的确切机制尚不清楚。最近的研究表明，线粒体功能障碍、氧化应激和炎症反应在 APAP 肝毒性的发病机制中起关键作用。自噬是一种分解代谢机制，旨在回收细胞成分和受损的细胞器，以响应各种刺激，如营养缺乏和毒性应激。越来越多的证据支持自噬参与了 APAP 诱导的肝损伤的病理生理过程。在这篇综述中，我们总结了 APAP 中毒后肝脏自噬的变化，并讨论了自噬在 APAP 肝毒性中的作用及其可能的机制。此外，本综述强调了线粒体自噬、氧化应激和炎症在 APAP 诱导的肝损伤中的相互作用，并提出了一些可能的分子机制，即激活的自噬可以防止 APAP 诱导的肝损伤。
