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On-line Access: 2022-04-11

Received: 2021-11-28

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Zhi Chen

https://orcid.org/0000-0002-0848-1502

Jingwen DENG

https://orcid.org/0000-0002-5340-4856

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Journal of Zhejiang University SCIENCE B 2022 Vol.23 No.4 P.265-285

http://doi.org/10.1631/jzus.B2100977


Molecular pathogenesis of acetaminophen-induced liver injury and its treatment options


Author(s):  Xiaopeng CAI, Huiqiang CAI, Jing WANG, Qin YANG, Jun GUAN, Jingwen DENG, Zhi CHEN

Affiliation(s):  State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; more

Corresponding email(s):   zjuchenzhi@zju.edu.cn, jwdeng@zju.edu.cn

Key Words:  Acetaminophen, Acetaminophen-induced liver injury, Hepatocyte necrosis, Sterile inflammation, Hepatocyte regeneration


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Xiaopeng CAI, Huiqiang CAI, Jing WANG, Qin YANG, Jun GUAN, Jingwen DENG, Zhi CHEN. Molecular pathogenesis of acetaminophen-induced liver injury and its treatment options[J]. Journal of Zhejiang University Science B, 2022, 23(4): 265-285.

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publisher="Zhejiang University Press & Springer",
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%A Xiaopeng CAI
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%J Journal of Zhejiang University SCIENCE B
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A1 - Huiqiang CAI
A1 - Jing WANG
A1 - Qin YANG
A1 - Jun GUAN
A1 - Jingwen DENG
A1 - Zhi CHEN
J0 - Journal of Zhejiang University Science B
VL - 23
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SP - 265
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B2100977


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.

对乙酰氨基酚诱导的肝损伤的分子发病机制及治疗策略

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。

关键词:对乙酰氨基酚;对乙酰氨基酚诱导的肝损伤;肝细胞坏死;无菌性炎症;肝细胞再生

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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