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

被引:37
作者
Cai, Xiaopeng [1 ]
Cai, Huiqiang [2 ]
Wang, Jing [1 ]
Yang, Qin [1 ]
Guan, Jun [1 ]
Deng, Jingwen [3 ,4 ]
Chen, Zhi [1 ]
机构
[1] Zhejiang Univ, Collaborat Innovat Ctr Diag & Treatment Infect Di, State Key Lab Diag & Treatment Infect Dis, Affiliated Hosp 1,Sch Med,Natl Clin Res Ctr Infec, Hangzhou 310003, Zhejiang, Peoples R China
[2] Univ Aarhus, Dept Clin Med, Palle Juul Jensens Blvd 82, DK-8200 Aarhus N, Denmark
[3] Zhejiang Univ, Dept Pathol, Sch Med, Key Lab Dis Prote Zhejiang Prov, Hangzhou 310058, Peoples R China
[4] Zhejiang Univ, Womens Hosp, Dept Pathol, Sch Med, Hangzhou 310058, Peoples R China
关键词
Acetaminophen; Acetaminophen-induced liver injury; Hepatocyte necrosis; Sterile inflammation; Hepatocyte regeneration; MITOCHONDRIAL PERMEABILITY TRANSITION; ACUTE INFLAMMATORY RESPONSE; NECROSIS-FACTOR RECEPTOR-1; ENDOTHELIAL GROWTH-FACTOR; INDUCED HEPATOTOXICITY; HEPATOCYTE-REGENERATION; KUPFFER CELLS; INFILTRATING MACROPHAGES; PATHOPHYSIOLOGICAL ROLE; GLUTATHIONE SYNTHESIS;
D O I
10.1631/jzus.B2100977
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:265 / 285
页数:21
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