Protective effect of grape seed and skin extract against high-fat diet-induced liver steatosis and zinc depletion in rat

Dig Dis Sci. 2014 Aug;59(8):1768-78. doi: 10.1007/s10620-014-3128-0. Epub 2014 Apr 6.


Background: Obesity is a tremendous public health problem, characterized by ectopic deposition of fat into non-adipose tissues as liver generating an oxidative stress that could lead to steato-hepatitis. Grape seed and skin extract (GSSE) is a complex mixture of polyphenolics exhibiting robust antioxidative properties.

Aim: We hypothesize that GSSE could protect the liver from fat-induced lipotoxicity and have a beneficial effect on liver function.

Methods: Hepatoprotective effect of GSSE was measured by using an experimental model of fat-induced rat liver steatosis. Male rats were fed a standard diet or a high-fat diet (HFD) during 6 weeks and treated or not with 500 mg/kg bw GSSE. Lipid deposition into the liver was assessed by triglyceride, cholesterol and phospholipid measurements. Fat-induced lipoperoxidation, carbonylation, depletion of glutathione and of antioxidant enzyme activities were used as oxidative stress markers with a special emphasis on transition metal distribution.

Results: HFD induced liver hypertrophy and inflammation as assessed by high liver transaminases. HFD also induced an oxidative stress characterized by increased lipid and protein oxidation, a drop in glutathione and antioxidant enzyme activities as glutathione peroxidase and superoxide dismutase and a drastic depletion in liver zinc. Importantly, GSSE prevented all the deleterious effects of HFD treatment.

Conclusions: Data suggest that GSSE could be used as a safe preventive agent against fat-induced liver lipotoxicity which could also have potential applications in other non-alcoholic liver diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Diet, High-Fat / adverse effects*
  • Fatty Liver / etiology
  • Fatty Liver / pathology
  • Fatty Liver / prevention & control*
  • Fruit / chemistry
  • Grape Seed Extract / chemistry
  • Grape Seed Extract / pharmacology
  • Grape Seed Extract / therapeutic use*
  • Lipid Metabolism / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Organ Size / drug effects
  • Phytotherapy*
  • Rats
  • Rats, Wistar
  • Vitis / chemistry*
  • Weight Gain / drug effects
  • Zinc / metabolism


  • Antioxidants
  • Grape Seed Extract
  • Zinc