Silymarin protects against acute ethanol-induced hepatotoxicity in mice

Alcohol Clin Exp Res. 2006 Mar;30(3):407-13. doi: 10.1111/j.1530-0277.2006.00063.x.


Background: Accumulated evidence has demonstrated that both oxidative stress and abnormal cytokine production, especially tumor necrosis factor-alpha (TNF), play important etiological roles in the pathogenesis of alcoholic liver disease (ALD). Agents that have both antioxidant and anti-inflammation properties, particularly anti-TNF production, represent promising therapeutic interventions for ALD. We investigated the effects and the possible mechanism(s) of silymarin on liver injury induced by acute ethanol (EtOH) administration.

Methods: Nine-week-old mice were divided into 4 groups, control, silymarin treatment, EtOH treatment, and silymarin/EtOH treatment, with 6 mice in each group. Because control and silymarin values were virtually identical, only control treatment is shown for ease of viewing. Ethanol-treated mice received EtOH [5 g/kg body weight (BW)] by gavage every 12 hours for a total of 3 doses. Control mice received an isocalorical maltose solution. In the silymarin/EtOH group, silymarin was dissolved in the EtOH and gavaged simultaneously with EtOH at a dose of 200 mg/kg BW. At 4 hours after the last dosing, the mice were anesthetized and subsequent serum alanine aminotransferase (ALT) level, hepatic lipid peroxidation, enzymatic activity of hepatic cytochrome P450 2E1, hepatic TNF-alpha, and glutathione (GSH) levels were measured. Histopathological change was assessed by hematoxylin and eosin staining.

Results: Acute EtOH administration caused prominent hepatic microvesicular steatosis with mild necrosis and an elevation of serum ALT activity, induced a significant decrease in hepatic GSH in conjunction with enhanced lipid peroxidation, and increased hepatic TNF production. Supplementation with a standardized silymarin attenuated these adverse changes induced by acute EtOH administration.

Conclusions: Silymarin protects against the liver injury caused by acute EtOH administration. In view of its nontoxic nature, it may be developed as an effective therapeutic agent for alcohol-induced liver disease by its antioxidative stress and anti-inflammatory features.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Antioxidants / therapeutic use*
  • Central Nervous System Depressants / toxicity*
  • Cytochrome P-450 CYP2E1 / metabolism
  • Ethanol / toxicity*
  • Glutathione / metabolism
  • Hepatitis, Alcoholic / metabolism
  • Hepatitis, Alcoholic / pathology
  • Hepatitis, Alcoholic / prevention & control*
  • Lipid Peroxidation / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Silymarin / therapeutic use*
  • Triglycerides / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • Antioxidants
  • Central Nervous System Depressants
  • Silymarin
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • Ethanol
  • Cytochrome P-450 CYP2E1
  • Alanine Transaminase
  • Glutathione