title: N-acetylcysteine attenuates lipopolysaccharide-induced apoptotic liver damage in D-galactosamine-sensitized mice.
abstract: OBJECTIVE
  To investigate the effects of N-acetylcysteine on D-galactosamine (GalN)/ lipopolysaccharide (LPS)-induced apoptotic liver injury in mice.
  
  
  METHODS
  When given together with a low dose of LPS, GalN highly sensitizes animals to produce apoptotic liver injury with severe hepatic congestion, resulting in rapid death. In the GalN/LPS model, TNF-alpha is the major mediator leading to apoptotic liver injury. Reactive oxygen species (ROS) are involved in GalN-induced sensitization to TNF-alpha-evoked hepatocyte apoptosis. N-acetylcysteine (NAC) is an antioxidant and a glutathione (GSH) precursor. In this study, we investigated the effects of NAC on LPS-induced apoptotic liver injury in GalN-sensitized mice.
  
  
  RESULTS
  Pretreatment with NAC significantly reduced GalN/LPS-induced elevation of serum alanine aminotransferase levels. In parallel, GalN/LPS-induced hepatic necrosis and congestion were obviously improved by NAC. Furthermore, NAC pretreatment significantly alleviated GalN/LPS-induced hepatic apoptosis, measured by the inhibition of hepatic caspase-3 activity and attenuation of DNA laddering. NAC pretreatment had no effect on LPS-evoked nitric oxide production in GalN-sensitized mice. Increases in serum TNF-alpha concentration, which were observed in GalN/LPS-treated mice, were not significantly reduced by NAC. Although NAC pretreatment significantly alleviated LPS-induced hepatic GSH depletion, DL-buthionine-(SR)-sulfoximine, an inhibitor of GSH synthesis, did not influence the protective effect of NAC on GalN/LPS-induced apoptotic liver injury.
  
  
  CONCLUSIONS
  NAC attenuates GalN/LPS-induced apoptotic liver injury via its strong ROS scavenging and anti-apoptotic effects.
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei 230032, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: De-xiang
authors.initials: DX
authors.lastname: Xu
authors.forename: Jin-wei
authors.initials: JW
authors.lastname: Lu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005688:Galactosamine / Q000008:administration & dosage / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000975:Antioxidants; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D005688:Galactosamine; D000111:Acetylcysteine