Polyenephosphatidylcholine prevents alcoholic liver disease in PPARalpha-null mice through attenuation of increases in oxidative stress

J Hepatol. 2009 Jun;50(6):1236-46. doi: 10.1016/j.jhep.2009.01.025. Epub 2009 Apr 2.


Background/aims: Alcoholic liver disease (ALD) is one of the leading causes of cirrhosis and yet efficient therapeutic strategies are lacking. Polyenephosphatidylcholine (PPC), a major component of essential phospholipids, prevented alcoholic liver fibrosis in baboons, but its precise mechanism remains uncertain. We aimed to explore the effects of PPC on ALD using ethanol-fed peroxisome proliferator-activated receptor alpha (Ppara)-null mice, showing several similarities to human ALD.

Methods: Male wild-type and Ppara-null mice were pair-fed a Lieber-DeCarli control or 4% ethanol-containing diet with or without PPC (30 mg/kg/day) for 6 months.

Results: PPC significantly ameliorated ethanol-induced hepatocyte damage and hepatitis in Ppara-null mice. These effects were likely a consequence of decreased oxidative stress through down-regulation of reactive oxygen species (ROS)-generating enzymes, including cytochrome P450 2E1, acyl-CoA oxidase, and NADPH oxidases, in addition to restoration of increases in Toll-like receptor 4 and CD14. PPC also decreased Bax and truncated Bid, thus inhibiting apoptosis. Furthermore, PPC suppressed increases in transforming growth factor-beta1 expression and hepatic stellate cell activation, which retarded hepatic fibrogenesis.

Conclusions: PPC exhibited anti-inflammatory, anti-apoptotic, and anti-fibrotic effects on ALD as a result of inhibition of the overexpression of ROS-generating enzymes. Our results demonstrate detailed molecular mechanisms of the anti-oxidant action of PPC.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Ethanol / metabolism
  • Ethanol / toxicity
  • Lipopolysaccharides / toxicity
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / prevention & control
  • Liver Diseases, Alcoholic / genetics
  • Liver Diseases, Alcoholic / metabolism
  • Liver Diseases, Alcoholic / pathology
  • Liver Diseases, Alcoholic / prevention & control*
  • Male
  • Mice
  • Mice, Knockout
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • PPAR alpha / deficiency*
  • PPAR alpha / genetics
  • Phosphatidylcholines / pharmacology*
  • Phosphotransferases / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects


  • Antioxidants
  • Lipopolysaccharides
  • NF-kappa B
  • PPAR alpha
  • Phosphatidylcholines
  • RNA, Messenger
  • polyene phosphatidylcholine
  • Ethanol
  • Phosphotransferases