Standardized Olea europaea L. leaf extract exhibits protective activity in carbon tetrachloride-induced acute liver injury in rats: the insight into potential mechanisms

Arch Physiol Biochem. 2020 Dec;126(5):399-407. doi: 10.1080/13813455.2018.1550095. Epub 2019 Jan 11.


The protective activity of dry olive leaf extract (DOLE) in carbon tetrachloride (CCl4)-induced liver damage and possible mechanisms involved in this protection were investigated in rats. Acute CCl4 intoxication resulted in a massive hepatic necrosis, in increased serum transaminases, and in a perturbation of oxidative stress parameters in liver tissue [malondyaldehide, glutathione (GSH), catalase]. CCl4 did not affect the expression of caspase-3 and cytochrome c as markers of apoptosis; however, CCl4 increased the AMP-activated protein kinase (AMPK) activity and the expression of autophagy-related protein LC3II and decreased the expression of p62 protein. The pre-treatment with DOLE significantly improved serum markers of liver damage, liver catalase activity, and GSH concentration, suggesting that antioxidative mechanism is responsible for hepatoprotection. Oral administration of DOLE did not influence LC3II conversion and p62 degradation in liver, but AMPK activity was significantly decreased, suggesting the energy balance perturbation as an additional potential mechanism of DOLE hepatoprotective effect.

Keywords: AMP-activated protein kinase; Liver toxicity; antioxidants; apoptosis; autophagy; hepatoprotection.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Carbon Tetrachloride / toxicity*
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Lipid Peroxidation / drug effects
  • Male
  • Olea / chemistry*
  • Oxidative Stress / drug effects
  • Plant Extracts / pharmacology*
  • Protective Agents / pharmacology*
  • Rats
  • Rats, Wistar


  • Antioxidants
  • Plant Extracts
  • Protective Agents
  • Carbon Tetrachloride