Astaxanthin alleviated ethanol-induced liver injury by inhibition of oxidative stress and inflammatory responses via blocking of STAT3 activity

Sci Rep. 2018 Sep 20;8(1):14090. doi: 10.1038/s41598-018-32497-w.

Abstract

Astaxanthin (AXT) is classified as a xanthophyll carotenoid compound which have broader functions including potent antioxidant, anti-inflammatory and neuroprotective properties. Considerable researches have demonstrated that AXT shows preventive and therapeutic properties against for Diabetes, Osteoarthritis and Rheumatoid Arthritis. However, the protective effect of AXT on liver disease has not yet been reported. In this study, we investigated effects of AXT on ethanol-induced liver injury in chronic plus binge alcohol feeding model. The hepatic steatosis and inflammation induced by ethanol administration were alleviated by AXT. Serum levels of aspartate transaminase and alanine transaminase were decreased in the livers of AXT administrated group. The ethanol-induced expression of cytochrome P450 2E1 (CYP2E1), pro-inflammatory proteins, cytokines, chemokines and reactive oxygen species (ROS) levels were also reduced in the livers of AXT administrated group. Moreover, ethanol-induced infiltration of neutrophils was decreased in the livers of AXT administrated group. Docking model and pull-down assay showed that AXT directly binds to the DNA binding site of STAT3. Moreover, AXT decreased STAT3 phosphorylation in the liver of AXT administration group. Therefore, these results suggest that AXT could prevent ethanol-induced hepatic injury via inhibition of oxidant and inflammatory responses via blocking of STAT3 activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Aspartate Aminotransferases / blood
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Ethanol / adverse effects
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Oxidative Stress / drug effects*
  • Phosphorylation / drug effects
  • Reactive Oxygen Species / metabolism
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Xanthophylls / pharmacology
  • Xanthophylls / therapeutic use

Substances

  • Antioxidants
  • Cytokines
  • Reactive Oxygen Species
  • STAT3 Transcription Factor
  • Xanthophylls
  • Ethanol
  • astaxanthine
  • Aspartate Aminotransferases