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Review
. 2023 Mar 27:14:1122632.
doi: 10.3389/fphar.2023.1122632. eCollection 2023.

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

Jiaqing Liao  1   2 , Qiuxia Lu  1   3 , Zhiqi Li  1   3 , Jintao Li  1   2 , Qi Zhao  1   3 , Jian Li  1   4
Affiliations
Review

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

Jiaqing Liao et al. Front Pharmacol. .

Abstract

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.

Keywords: Nrf2; acetaminophen; liver injury; natural products; oxidative stress.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Metabolites protect against acetaminophen-induced hepatotoxicity.
FIGURE 2
FIGURE 2
Chemical structures of potential metabolites for the treatment of acetaminophen-induced liver injury.
See this image and copyright information in PMC

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