Propolis protects CYP 2E1 enzymatic activity and oxidative stress induced by carbon tetrachloride

Mol Cell Biochem. 2007 Aug;302(1-2):215-24. doi: 10.1007/s11010-007-9443-4. Epub 2007 Apr 5.


Induction of CYP 2E1 by carbon tetrachloride (CCl(4)) is one of the central pathways by which CCl(4) generates oxidative stress in hepatocytes. Experimental liver injury was induced in rats by CCl(4) to determine toxicological actions on CYP 2E1 by microsomal drug metabolizing enzymes. In this report, ethanolic extract of propolis at a dose of 200 mg/kg (po) was used after 24 h of toxicant administration to validate its protective potential. Intraperitoneal injection of CCl(4) (1.5 ml/kg) induced hepatotoxicity after 24 h of its administration that was associated with elevated malonyldialdehyde (index of lipid peroxidation), lactate dehydrogenase and gamma-glutamyl transpeptidase release (index of a cytotoxic effect). Hepatic microsomal drug metabolizing enzymes of CYP 2E1 showed sharp depletion as assessed by estimating aniline hydroxylase and amidopyrine N-demethylase activity after CCl(4) exposure. Toxic effect of CCl(4) was evident on CYP 2E1 activity by increased hexobarbitone induced sleep time and bromosulphalein retention. Propolis extract showed significant improvement in the activity of both enzymes and suppressed toxicant induced increase in sleep time and bromosulphalein retention. Choleretic activity of liver did not show any sign of toxicity after propolis treatment at a dose of 200 mg/kg (id). Histopathological evaluation of the liver revealed that propolis reduced the incidence of liver lesions including hepatocyte swelling and lymphocytic infiltrations induced by CCl(4). Electron microscopic observations also showed improvement in ultrastructure of liver and substantiated recovery in biochemical parameters. Protective activity of propolis at 200 mg/kg dose was statistically compared with positive control silymarin (50 mg/kg, po), a known hepatoprotective drug seems to be better in preventing hepatic CYP 2E1 activity deviated by CCl(4). These results lead us to speculate that propolis may play hepatoprotective role via improved CYP 2E1 activity and reduced oxidative stress in living system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyrine N-Demethylase / metabolism
  • Aniline Hydroxylase / metabolism
  • Animals
  • Carbon Tetrachloride / toxicity*
  • Cholagogues and Choleretics / pharmacology
  • Cytochrome P-450 CYP2E1 / metabolism*
  • Hexobarbital / pharmacology
  • L-Lactate Dehydrogenase / blood
  • Lipid Peroxidation / drug effects
  • Liver / enzymology
  • Liver / pathology
  • Liver / ultrastructure
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • Oxidative Stress / drug effects*
  • Propolis / pharmacology*
  • Protective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Rest
  • Sleep / drug effects
  • gamma-Glutamyltransferase / blood


  • Cholagogues and Choleretics
  • Protective Agents
  • Propolis
  • Hexobarbital
  • Carbon Tetrachloride
  • L-Lactate Dehydrogenase
  • Cytochrome P-450 CYP2E1
  • Aniline Hydroxylase
  • Aminopyrine N-Demethylase
  • amidopyrine N-demethylase
  • gamma-Glutamyltransferase