Mechanism for the protective effects of silymarin against carbon tetrachloride-induced lipid peroxidation and hepatotoxicity in mice. Evidence that silymarin acts both as an inhibitor of metabolic activation and as a chain-breaking antioxidant

Biochem Pharmacol. 1990 Jun 15;39(12):2027-34. doi: 10.1016/0006-2952(90)90625-u.


Administration of silymarin (800 mg/kg i.p.) 30 min before carbon tetrachloride (18 microL/kg i.p.) did not modify total hepatic levels of CCl4 and metabolites in mice, but decreased by 40% the in vivo covalent binding of CCl4 metabolites to hepatic lipids at 2 hr. This pretreatment decreased by 60% the exhalation of ethane during the first hour after CCl4, and decreased by 50% the incidence of liver cell necrosis. In vitro, silymarin (800 micrograms/mL) decreased by 50 to 70% various monooxygenase activities, and decreased by 20% the covalent binding of CCl4 metabolites to microsomal proteins. Silymarin (800 micrograms/mL) decreased by 70% in vitro lipid peroxidation mediated by CCl4 metabolites, and decreased by 90% peroxidation mediated by NADPH alone. Silibinin, one of the three isomers composing silymarin, also decreased carbon tetrachloride-induced lipid peroxidation; this effect, however, was less than that of silymarin in vitro, and was more transient in vivo. Pretreatment with silibinin (800 mg/kg i.p.) 30 min before CCl4 (18 microL/kg i.p.) did not improve SGPT activity or liver histology at 24 hr. We conclude that silymarin prevents carbon tetrachloride-induced lipid peroxidation and hepatotoxicity in mice, firstly, by decreasing the metabolic activation of CCl4, and, secondly, by acting as a chain-breaking antioxidant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 7-Alkoxycoumarin O-Dealkylase / metabolism
  • Alanine Transaminase / blood
  • Animals
  • Antioxidants / pharmacology*
  • Binding, Competitive
  • Carbon Tetrachloride / antagonists & inhibitors*
  • Carbon Tetrachloride / toxicity
  • Flavonoids / pharmacology*
  • Injections, Intraperitoneal
  • Lipid Peroxidation / drug effects*
  • Liver / drug effects*
  • Liver / pathology
  • Male
  • Mice
  • Silymarin / pharmacology*


  • Antioxidants
  • Flavonoids
  • Silymarin
  • Carbon Tetrachloride
  • 7-Alkoxycoumarin O-Dealkylase
  • Alanine Transaminase