title: Dietary Fisetin Supplementation Protects Against Alcohol-Induced Liver Injury in Mice.
abstract: Overproduction of reactive oxygen species is associated with the development of alcoholic liver disease (ALD). Plant polyphenols have been used as dietary interventions for multiple diseases including ALD. The objective of this study was to determine whether dietary supplementation with fisetin, a novel flavonoid, exerts beneficial effect on alcohol-induced liver injury.
  
  
  
  C57BL/6J mice were pair-fed with the Lieber-DeCarli control or ethanol (EtOH) diet for 4 weeks with or without fisetin supplementation at 10 mg/kg/d.
  
  
  
  Alcohol feeding induced lipid accumulation in the liver and increased plasma alanine aminotransferase and aspartate aminotransferase activities, which were attenuated by fisetin supplementation. The EtOH concentrations in the plasma and liver were significantly elevated by alcohol exposure but were reduced by fisetin supplementation. Although fisetin did not affect the protein expression of alcohol metabolism enzymes, the aldehyde dehydrogenase activities were significantly increased by fisetin compared to the alcohol alone group. In addition, fisetin supplementation remarkably reduced hepatic NADPH oxidase 4 levels along with decreased plasma hydrogen peroxide and hepatic superoxide and 4-hydroxynonenal levels after alcohol exposure. Alcohol-induced apoptosis and up-regulation of Fas and cleaved caspase-3 in the liver were prevented by fisetin. Moreover, fisetin supplementation attenuated alcohol-induced hepatic steatosis through increasing plasma adiponectin levels and hepatic protein levels of p-AMPK, ACOX1, CYP4A, and MTTP.
  
  
  
  This study demonstrated that the protective effect of fisetin on ALD is achieved by accelerating EtOH clearance and inhibition of oxidative stress. The data suggest that fisetin has a therapeutical potential for treating ALD.
authors: Department of Nutrition, University of North Carolina at Greensboro, Kannapolis, North Carolina.|Center for Translational Biomedical Research, University of North Carolina at Greensboro, Kannapolis, North Carolina.
authors: Qian
authors: Q
authors: Sun
authors: Center for Translational Biomedical Research, University of North Carolina at Greensboro, Kannapolis, North Carolina.
authors: Wenliang
authors: W
authors: Zhang
authors: Center for Translational Biomedical Research, University of North Carolina at Greensboro, Kannapolis, North Carolina.
authors: Wei
authors: W
authors: Zhong
authors: Center for Translational Biomedical Research, University of North Carolina at Greensboro, Kannapolis, North Carolina.
authors: Xinguo
authors: X
authors: Sun
authors: Department of Nutrition, University of North Carolina at Greensboro, Kannapolis, North Carolina. z_zhou@uncg.edu.|Center for Translational Biomedical Research, University of North Carolina at Greensboro, Kannapolis, North Carolina. z_zhou@uncg.edu.
authors: Zhanxiang
authors: Z
authors: Zhou
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D042962:Acyl-CoA Oxidase / Q000378:metabolism; D052242:Adiponectin / Q000097:blood; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D042926:Cytochrome P-450 CYP4A / Q000378:metabolism; D019587:Dietary Supplements; D000431:Ethanol / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D005234:Fatty Liver / Q000150:complications / Q000178:diet therapy; D005419:Flavonoids / Q000627:therapeutic use*; D044948:Flavonols; D006861:Hydrogen Peroxide / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000097:blood / Q000150:complications / Q000178:diet therapy* / Q000201:enzymology; D008297:Male; D051379:Mice; D000074663:NADPH Oxidase 4 / Q000378:metabolism; D020011:Protective Agents / Q000627:therapeutic use; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D052242:Adiponectin; D000447:Aldehydes; D002352:Carrier Proteins; D005419:Flavonoids; D044948:Flavonols; D020011:Protective Agents; C106092:microsomal triglyceride transfer protein; D013481:Superoxides; D000431:Ethanol; D006861:Hydrogen Peroxide; D042926:Cytochrome P-450 CYP4A; D000444:Aldehyde Dehydrogenase; C000625549:ACOX1 protein, mouse; D042962:Acyl-CoA Oxidase; D000074663:NADPH Oxidase 4; C422943:Nox4 protein, mouse; D055372:AMP-Activated Protein Kinases; C027576:4-hydroxy-2-nonenal; C017875:fisetin
keywords: Alcoholic Liver Disease; Apoptosis; Fatty Liver; Fisetin; Oxidative Stress