Fisetin Prevents Acetaminophen-Induced Liver Injury by Promoting Autophagy

Acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure in clinical and hospital settings. Fisetin (FST) is a phenolic compound derived from natural products such as fruit and vegetables. Our research investigated the protective mechanisms of FST in APAP-induced hepatic...

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Published inFrontiers in pharmacology Vol. 11; p. 162
Main Authors Zhang, Jiaqi, Zhao, Licong, Hu, Cheng, Wang, Tao, Lu, Juan, Wu, Chenqu, Chen, Long, Jin, Mingming, Hu, Hao, Ji, Guang, Cao, Qin, Jiang, Yuanye
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 28.02.2020
Subjects
acetaminophen
ATG5
autophagy
fisetin
liver injury
Pharmacology
fisetin
acetaminophen
liver injury
autophagy
ATG5
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Summary:Acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure in clinical and hospital settings. Fisetin (FST) is a phenolic compound derived from natural products such as fruit and vegetables. Our research investigated the protective mechanisms of FST in APAP-induced hepatic injury and . Assessment of mouse serum levels of alanine/aspartate aminotransferases (ALT/AST), liver myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) demonstrated the protective effects of FST toward APAP-induced liver injury. FST also reversed an APAP-induced decrease in mouse L-02 cell line viability. Our results also showed that FST significantly promoted APAP-induced autophagy and inhibited inflammasome activation both and . We also found that silencing ATG5, using si-ATG5, reduced the protective effects of FST against APAP-induced hepatotoxicity and reversed the effects on autophagy. Finally, we used the autophagy inhibitor, 3-methyladenine (3-MA) to validate the involvement of autophagy in FST against APAP-induced hepatotoxicity . We demonstrated that FST prevented APAP-induced hepatotoxicity by increasing ATG5 expression, thereby promoting autophagy and inhibiting inflammasome activation.
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This article was submitted to Gastrointestinal and Hepatic Pharmacology, a section of the journal Frontiers in Pharmacology
Edited by: Raffaele Capasso, University of Naples Federico II, Italy
These authors have contributed equally to this work
Reviewed by: Yan Zhao, Jilin Agricultural University, China; Jingyuan Wan, Chongqing Medical University, China
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2020.00162