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

• 作者: Xiaopeng CAI Huiqiang CAI Jing WANG Qin YANG Jun GUAN Jingwen DENG Zhi CHEN
• 来源期刊: 浙江大学学报（英文版）（B辑：生物医学和生物技术）
• 年，卷（期）: 2022,（4）
• 所属期刊栏目: Review
• 页码范围: 265-285
• 页数: 21页
• 语种: 英文

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.