S-allylmercaptocysteine reduces carbon tetrachloride-induced hepatic oxidative stress and necroinflammation via nuclear factor kappa B-dependent pathways in mice

Eur J Nutr. 2012 Apr;51(3):323-33. doi: 10.1007/s00394-011-0217-0. Epub 2011 Jun 18.

Abstract

Purpose: To study the protective effects and underlying molecular mechanisms of SAMC on carbon tetrachloride (CCl4)-induced acute hepatotoxicity in the mouse model.

Methods: Mice were intraperitoneally injected with CCl4 (50 μl/kg; single dose) to induce acute hepatotoxicity with or without a 2-h pre-treatment of SAMC intraperitoneal injection (200 mg/kg; single dose). After 8 h, the blood serum and liver samples of mice were collected and subjected to measurements of histological and molecular parameters of hepatotoxicity.

Results: SAMC reduced CCl4-triggered cellular necrosis and inflammation in the liver under histological analysis. Since co-treatment of SAMC and CCl4 enhanced the expressions of antioxidant enzymes, reduced the nitric oxide (NO)-dependent oxidative stress, and inhibited lipid peroxidation induced by CCl4. SAMC played an essential antioxidative role during CCl4-induced hepatotoxicity. Administration of SAMC also ameliorated hepatic inflammation induced by CCl4 via inhibiting the activity of NF-κB subunits p50 and p65, thus reducing the expressions of pro-inflammatory cytokines, mediators, and chemokines, as well as promoting pro-regenerative factors at both transcriptional and translational levels.

Conclusions: Our results indicate that SAMC mitigates cellular damage, oxidative stress, and inflammation in CCl4-induced acute hepatotoxicity mouse model through regulation of NF-κB. Garlic or garlic derivatives may therefore be a potential food supplement in the prevention of liver damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Antioxidants / pharmacology
  • Carbon Tetrachloride / toxicity*
  • Chemical and Drug Induced Liver Injury / pathology*
  • Cysteine / analogs & derivatives*
  • Cysteine / pharmacology
  • Female
  • Inflammation / chemically induced
  • Inflammation / pathology
  • Inflammation / prevention & control*
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Malondialdehyde / blood
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism*
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects*

Substances

  • Antioxidants
  • NF-kappa B
  • S-allylmercaptocysteine
  • Nitric Oxide
  • Malondialdehyde
  • Carbon Tetrachloride
  • Alanine Transaminase
  • Cysteine