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

Jiaqing Liao; Qiuxia Lu; Zhiqi Li; Jintao Li; Qi Zhao; Jian Li

doi:10.3389/fphar.2023.1122632

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

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

Authors

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

¹ Engineering Research Center of Sichuan-Tibet Traditional Medicinal Plant, Chengdu University, Chengdu, China.
² School of Pharmacy, Chengdu University, Chengdu, China.
³ School of Food and Biological Engineering, Chengdu University, Chengdu, China.
⁴ School of Basic Medical Sciences, Chengdu University, Chengdu, China.

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.

Publication types

Review

Grants and funding

This study was supported by the National Natural Science Foundation of China to QZ (No.32270407) and the open fund of State Key Laboratory of Southwestern Chinese Medicine Resources (No.SCMR202103) and Natural Science Foundation of Sichuan (No.2022NSFSC0583) to JL.