Research progress on regulation of mitochondrial function by traditional Chinese medicine in alleviating acetaminophen-induced liver injury

Abstract

Drug-induced liver injury is a significant contributor to cases of acute liver failure and the primary reason for drug withdrawal due to safety concerns. Acetaminophen (N-acetyl-para-aminophenol, APAP) is a widely used antipyretic and analgesic drug worldwide. It has been reported that APAP-induced hepatotoxicity accounts for approximately 50 % of acute liver failure cases in Europe and the United States. Currently, N-acetylcysteine is still the only drug approved for the treatment of APAP-induced hepatotoxicity. Nevertheless, its restricted therapeutic window constrains its clinical utility. There is an urgent need to find new drugs for the prevention and treatment of APAP-induced liver failure. Mitochondria are the main toxic targets of APAP, playing important roles in the injury, progression, and recovery stages of its hepatotoxicity. Excessive poisonous metabolites of APAP, such as N-acetyl-benzoquinone imine (NAPQI), can bind to mitochondrial proteins, inducing mitochondrial oxidative stress and changes in membrane permeability, leading to the release of pro-apoptotic factors into the nucleus and causing hepatocyte death. Mitochondrial fusion and fission, autophagy, and biogenesis collectively constitute the mitochondrial quality control system, which plays an important role in maintaining mitochondrial homeostasis and resisting APAP hepatotoxicity. Traditional Chinese medicine (TCM) is a treasure of the Chinese nation, with many herbal medicines used clinically for liver protection. Previous reviews summarized that TCM exerted its protective effects by reducing oxidative stress, combating inflammation and anti-apoptotic pathways. However, few reviews highlighted the regulating effects of TCM on mitochondrial function. This review focuses on elucidating the effects of TCM on regulating mitochondrial oxidative stress and mitochondrial quality control system and preventing APAP-induced liver failure, providing a theoretical basis for developing preventive and therapeutic drugs for APAP-induced liver failure from TCM in the future.

Keywords

Traditional Chinese medicine / Acetaminophen / Mitochondria / Liver injury

Declarations

Not applicable.

Authors' contributions

Conceptualization: MY, HG; methodology: SX, RC; formal analysis and investigation: SX, RC; writing, original draft preparation: SX, RC; writing, review, and editing: SX, RC, ZYH, JYL, XXF, ZCJ, HG, MY; funding acquisition: MY; resources: HG; supervision: MY, HG.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent for publication was obtained from all participants.

Availability of data and materials

Not applicable.

Funding

This study was supported by the National Natural Science Foundation of China (No. 81974532), the Science Fund for Distinguished Young Scholars of Hunan Province (No. 2022JJ10097), the Natural Science Foundation of Hunan Province (No. 2023JJ60351), Postgraduate Innovative Project of Central South University (No. 2023XQLH120), and Postgraduate Innovative Project of Central South University (No. 2024XQLH030).

Declaration of Competing Interest

All authors have no conflicts of interest that are directly relevant to the content of this study.

Acknowledgements

Not applicable.

Authors' other information

Not applicable.

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