Acetaminophen-induced liver injury: Molecular mechanism and treatments from natural products

Acetaminophen (APAP) is a widely used analgesic and antipyretic over-the-counter medicine worldwide. Hepatotoxicity caused by APAP overdose is one of the leading causes of acute liver failure (ALF) in the US and in some parts of Europe, limiting its clinical application. Excessive APAP metabolism de...

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Published inFrontiers in pharmacology Vol. 14; p. 1122632
Main Authors Liao, Jiaqing, Lu, Qiuxia, Li, Zhiqi, Li, Jintao, Zhao, Qi, Li, Jian
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 27.03.2023
Subjects
acetaminophen
liver injury
natural products
Nrf2
oxidative stress
Pharmacology
natural products
acetaminophen
liver injury
Nrf2
oxidative stress
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Summary:Acetaminophen (APAP) is a widely used analgesic and antipyretic over-the-counter medicine worldwide. Hepatotoxicity caused by APAP overdose is one of the leading causes of acute liver failure (ALF) in the US and in some parts of Europe, limiting its clinical application. Excessive APAP metabolism depletes glutathione and increases N-acetyl-p-benzoquinoneimide (NAPQI) levels, leading to oxidative stress, DNA damage, and cell necrosis in the liver, which in turn leads to liver damage. Studies have shown that natural products such as polyphenols, terpenes, anthraquinones, and sulforaphane can activate the hepatocyte antioxidant defense system with Nrf2 as the core player, reduce oxidative stress damage, and protect the liver. As the key enzyme metabolizing APAP into NAPQI, cytochrome P450 enzymes are also considered to be intriguing target for the treatment of APAP-induced liver injury. Here, we systematically review the hepatoprotective activity and molecular mechanisms of the natural products that are found to counteract the hepatotoxicity caused by APAP, providing reference information for future preclinical and clinical trials of such natural products.
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This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology
Edited by: Enrico Sangiovanni, University of Milan, Italy
Andres A. Caro, Hendrix College, United States
Reviewed by: Ayaz Shahid, Western University of Health Sciences, United States
These authors have contributed equally to this work and share first authorship
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2023.1122632