title: Protective effect of artichoke leaf extract against paracetamol-induced hepatotoxicity in rats.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  These results suggest that ALE may protect from paracetamol-induced liver toxicity via its antioxidant and anti-apoptotic properties.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan University , Ein Helwan, Cairo , Egypt.
authors.forename: Engy M
authors.initials: EM
authors.lastname: El Morsy
authors.forename: Rehab
authors.initials: R
authors.lastname: Kamel
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020552:Comet Assay; D031943:Cynara scolymus / Q000737:chemistry*; D004249:DNA Damage / Q000187:drug effects; D008111:Liver Function Tests; D008297:Male; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000302:isolation & purification / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D010936:Plant Extracts; D000082:Acetaminophen
keywords: Apoptosis; N-acetylcysteine; glutathione; oxidative stress