Silymarin protects against acute ethanol-induced hepatotoxicity in mice.

Abstract

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.

• Authors: Zhenyuan Song, Ion Deaciuc, Ming Song, David Y-W Lee, Yanze Liu, Xiaosheng Ji, Craig McClain
• Journal: Alcoholism, clinical and experimental research (Alcohol Clin Exp Res) Vol. 30 Issue 3 Pg. 407-13 (Mar 2006) ISSN: 0145-6008 [Print] England
• PMID: 16499481 (Publication Type: Journal Article)

Chemical References

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

Topics

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