Abstract
Acetaminophen, also known as N-acetyl-p-aminophenol (APAP), is commonly used as an antipyretic and analgesic agent. APAP overdose can induce hepatic toxicity, known as acetaminophen-induced liver injury (AILI). However, therapeutic doses of APAP can also induce AILI in patients with excessive alcohol intake or who are fasting. Hence, there is a need to understand the potential pathological mechanisms underlying AILI. In this review, we summarize three main mechanisms involved in the pathogenesis of AILI: hepatocyte necrosis, sterile inflammation, and hepatocyte regeneration. The relevant factors are elucidated and discussed. For instance, N-acetyl-p-benzoquinone imine (NAPQI) protein adducts trigger mitochondrial oxidative/nitrosative stress during hepatocyte necrosis, danger-associated molecular patterns (DAMPs) are released to elicit sterile inflammation, and certain growth factors contribute to liver regeneration. Finally, we describe the current potential treatment options for AILI patients and promising novel strategies available to researchers and pharmacists. This review provides a clearer understanding of AILI-related mechanisms to guide drug screening and selection for the clinical treatment of AILI patients in the future.
摘要
对乙酰氨基酚(APAP)在临床上应用广泛, 常用作解热镇痛剂。但APAP过量常常引起肝毒性, 称为对乙酰氨基酚诱导的肝损伤(AILI)。因此, 有必要了解AILI的病理机制, 用以预防和治疗AILI。这篇综述总结讨论了AILI三个主要发病机制:肝细胞坏死、无菌性炎症和肝细胞再生, 并且总结了当前有发展前景的AILI治疗方法, 以指导患者临床用药。
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This work was supported by the National Science and Technology Major Project of China (Nos. 2018ZX10302206 and 2017ZX10202203).
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Xiaopeng CAI and Huiqiang CAI wrote the manuscript. Jing WANG, Qin YANG, and Jun GUAN did the data collection. Jingwen DENG and Zhi CHEN were responsible for conceptualization and manuscript revision. All authors have read and approved the final manuscript, and therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
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Xiaopeng CAI, Huiqiang CAI, Jing WANG, Qin YANG, Jun GUAN, Jingwen DENG, and Zhi CHEN declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
This article does not contain any studies with human or animal subjects performed by any of the authors.
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Cai, X., Cai, H., Wang, J. et al. Molecular pathogenesis of acetaminophen-induced liver injury and its treatment options. J. Zhejiang Univ. Sci. B 23, 265–285 (2022). https://doi.org/10.1631/jzus.B2100977
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DOI: https://doi.org/10.1631/jzus.B2100977
Key words
- Acetaminophen
- Acetaminophen-induced liver injury
- Hepatocyte necrosis
- Sterile inflammation
- Hepatocyte regeneration