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

Xiaopeng Cai; Huiqiang Cai; Jing Wang; Qin Yang; Jun Guan; Jingwen Deng; Zhi Chen

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

Author: Xiaopeng CAI ¹ ; Huiqiang CAI ² ; Jing WANG ¹ ; Qin YANG ¹ ; Jun GUAN ¹ ; Jingwen DENG ³ ; Zhi CHEN ⁴
Author Information

1. 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.
2. Department of Clinical Medicine, University of Aarhus, Palle Juul-Jensens Boulevard 82, 8200 Aarhus N, Denmark.
3. Department of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China. zjuchenzhi@zju.edu.cn, jwdeng@zju.edu.cn.
4. 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. zjuchenzhi@zju.edu.cn.
Publication Type:Review
Keywords: Acetaminophen; Acetaminophen-induced liver injury; Hepatocyte necrosis; Hepatocyte regeneration; Sterile inflammation
MeSH: Acetaminophen/toxicity*; Analgesics, Non-Narcotic/toxicity*; Animals; Chemical and Drug Induced Liver Injury/pathology*; Chemical and Drug Induced Liver Injury, Chronic/pathology*; Humans; Inflammation/metabolism*; Liver/pathology*; Mice; Mice, Inbred C57BL; Necrosis/pathology*
From: Journal of Zhejiang University. Science. B 2022;23(4):265-285
CountryChina
Language:English
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.