The timing and effects of low-dose ethanol treatment on acetaminophen-induced liver injury

Fu Chao Liu, Huang Ping Yu, Chia Chih Liao, An Hsun Chou, Hung Chen Lee*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

5 Scopus citations


Acetaminophen (APAP) overdose is the major cause of drug-induced liver injury and acute liver failure. Approximately 10% of APAP is metabolized by cytochrome P450 (CYP2E1) into toxic N-acetyl-p-benzoquinone imine (NAPQI). CYP2E1 also contributes to ethanol metabolism, especially during conditions of high blood ethanol concentration. Acute and chronic ethanol consumption appears to have opposite effects on APAP-induced liver injury. We determined the effects of different doses, pre-and post-treatment, and various schedules of ethanol exposure in APAP-induced liver injury. Treatment with ethanol (0.5 g/kg) after 1 h of APAP (300 mg/kg) administration decreased serum ALT levels, histopathological features, and inflammatory cell infiltration. Moreover, ethanol treatment 1 h after APAP treatment reduced APAP-induced liver injury compared with later administration. Interestingly, ethanol pretreatment did not provide any protective effect. Furthermore, ethanol treatment was associated with a significant decrease in ERK and AKT phosphorylation during the acute injury phase. Ethanol exposure also increased CYP2E1 expression and decreased PCNA expression during the liver regeneration phase.

Original languageEnglish
Article number1094
Issue number10
StatePublished - 10 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Acetaminophen
  • Alcohol
  • CYP2E1
  • Cytochrome P450
  • Ethanol
  • Inflammation
  • Liver injury
  • Neutrophil


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