Protective effect of artichoke leaf extract against paracetamol-induced hepatotoxicity in rats

Pharm Biol. 2015 Feb;53(2):167-73. doi: 10.3109/13880209.2014.913066. Epub 2014 Sep 22.


Context: Paracetamol overdose is a predominant cause of hepatotoxicity in both humans and experimental animals.

Objective: In this study, we investigated the protective effect of aqueous artichoke leaf extract (ALE) against paracetamol-induced liver injury in rats using N-acetylcysteine (NAC) as a reference drug.

Materials and methods: Rats were divided into five groups: negative control, paracetamol (2 g/kg, single oral dose), ALE (1.5 g/kg, orally for 14 d), ALE + paracetamol, and NAC (100 mg/kg) + paracetamol. Indices of liver damage (serum alanine aminotransferase and aspartate aminotransferase) were measured. Liver homogenates were analyzed for oxidative stress biomarkers (MDA, malondialdehyde; SOD activity, superoxide dismutase activity; NO, nitric oxide; GSH content, reduced glutathione), glutathione cycling (GR, glutathione reductase), and utilization (GST, glutathione-S-transferase). Apoptosis was assessed using the comet assay.

Results: Paracetamol caused marked liver damage as noted by significant increased activities of serum aminotransferases (p < 0.05) as well as a significant increase in hepatic MDA and NO levels (p < 0.001) compared with the negative control group. GSH content, GR, GST, and SOD activities were decreased significantly (p < 0.001). Comet assay parameters (tail length, percentage of tailed cells, percentage of migrated DNA, and tail moment) were increased (p < 0.05), indicating apoptosis. Histopathological examination showed necrotic areas. Pre-treatment with ALE replenished hepatic GSH, reversed oxidative stress parameters, DNA damage, and necrosis induced by paracetamol.

Discussion and conclusion: These results suggest that ALE may protect from paracetamol-induced liver toxicity via its antioxidant and anti-apoptotic properties.

Keywords: Apoptosis; N-acetylcysteine; glutathione; oxidative stress.

MeSH terms

  • Acetaminophen / toxicity*
  • Animals
  • Antioxidants / isolation & purification
  • Antioxidants / therapeutic use*
  • Apoptosis / drug effects
  • Biomarkers / metabolism
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Comet Assay
  • Cynara scolymus / chemistry*
  • DNA Damage / drug effects
  • Liver Function Tests
  • Male
  • Necrosis
  • Oxidative Stress / drug effects
  • Plant Extracts / isolation & purification
  • Plant Extracts / therapeutic use*
  • Plant Leaves / chemistry
  • Rats, Sprague-Dawley


  • Antioxidants
  • Biomarkers
  • Plant Extracts
  • Acetaminophen