title: Hepatoprotective activity of Lepidium sativum seeds against D-galactosamine/lipopolysaccharide induced hepatotoxicity in animal model.
abstract: BACKGROUND
  Fulminant hepatic failure (FHF) is clinical syndrome with very poor prognosis and high mortality there is urgent need for the development of safe and non-toxic hepatoprotective agents for the adequate management of hepatitis. Hepatoprotective effect of the Lepidium sativum ethanolic extract (LSEE) was assessed by D-galactosamine-induced/lipopolysaccharide (400 mg/kg and 30 μg/kg) liver damage model in rats.
  
  
  METHODS
  Hepatoprotective activity of LSEE (150 and 300 mg/kg) and silymarin on D-GalN/LPS induced FHF in rat was assessed using several liver function enzyme parameters. Antioxidant properties as antioxidant stress enzymes were assessed in hepatic Liver as well as mRNA expression of cytokines genes such as TNF-α, IL-6, and IL-10 and stress related genes iNOS and HO-1 were determined by RT-PCR. Protein expression of apoptotic genes were evaluated through western blot. MPO and NF-κB DNA-binding activity was analyzed by ELISA. The magnitude of hepatic impairment was investigated through histopathological evaluation.
  
  
  RESULTS
  Marked amelioration of hepatic injuries by attenuation of serum and lipid peroxidation has been observed as comparable with silymarin (25 mg/kg p.o). D-GalN/LPS induced significant decrease in oxidative stress markers protein level, and albumin. LSEE significantly down-regulated the D-GalN/LPS induced pro-inflammatory cytokines TNFα and IL-6 mRNA expression in dose dependent fashion about 0.47 and 0.26 fold and up-regulates the IL-10 by 1.9 and 2.8 fold, respectively. While encourages hepatoprotective activity by down-regulating mRNA expression of iNOS and HO-1. MPO activity and NF-κB DNA-binding effect significantly increased and was mitigated by LSEE in a dose-dependent style as paralleled with silymarin.
  
  
  CONCLUSIONS
  Our data suggests that pretreatment of LSEE down regulates the caspase 3 and up-regulates the BCl2protein expression. The above findings revealed that Lepidium sativum has significant hepatoprotective activity.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh, 11451, Saudi Arabia. mraish@ksu.edu.sa.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Raish
authors.affiliation: Clinical Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
authors.forename: Ajaz
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Clinical Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia. alkharfy@ksu.edu.sa.
authors.forename: Khalid M
authors.initials: KM
authors.lastname: Alkharfy
authors.affiliation: Research Centre, King Saud University, Riyadh, 11451, Saudi Arabia.
authors.forename: Syed Rizwan
authors.initials: SR
authors.lastname: Ahamad
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh, 11451, Saudi Arabia.
authors.forename: Kazi
authors.initials: K
authors.lastname: Mohsin
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh, 11451, Saudi Arabia.
authors.forename: Fahad I
authors.initials: FI
authors.lastname: Al-Jenoobi
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh, 11451, Saudi Arabia.
authors.forename: Abdullah M
authors.initials: AM
authors.lastname: Al-Mohizea
authors.affiliation: Pharmacology College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
authors.forename: Mushtaq Ahmad
authors.initials: MA
authors.lastname: Ansari
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D004195:Disease Models, Animal; D005688:Galactosamine; D031220:Lepidium sativum; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000517:prevention & control*; D008111:Liver Function Tests; D008297:Male; D008517:Phytotherapy; D028321:Plant Preparations / Q000627:therapeutic use*; D020011:Protective Agents / Q000494:pharmacology*; D017208:Rats, Wistar; D012639:Seeds
chemical_list: D008070:Lipopolysaccharides; D028321:Plant Preparations; D020011:Protective Agents; D005688:Galactosamine
keywords: Cytokines; D-galactosamine/lipopolysaccharide; Hepatotoxicity; Lepidium sativum