title: Antifibrotic and antioxidant effects of N-acetylcysteine in an experimental cholestatic model.
abstract: OBJECTIVE
  Several studies have suggested that oxidative stress may play an important role in the pathogenesis of hepatic injury during cholestasis in rats and humans. The aim of this study was to evaluate the ability of N-acetylcysteine (NAC) to prevent the damage induced by bile duct ligation (BDL) for 28 days in male Wistar rats.
  
  
  METHODS
  NAC was administered daily (300 mg/kg, orally) for 28 days. Alanine aminotransferase was quantified in the serum; lipid peroxidation, glutathione, and catalase activity were measured in the liver. Fibrosis was assessed by measuring the liver hydroxyproline content; transforming growth factor-β (TGF-β), interleukin (IL)-6, and IL-10 were determined in the liver by a western blot and quantified densitometrically.
  
  
  RESULTS
  The induction of cholestatic damage by BDL was associated with an increase in alanine aminotransferase. Oxidative stress was also evaluated; lipid peroxidation increased, whereas the liver glutathione content and catalase activity decreased by BDL. NAC treatment prevented these alterations. Hydroxyproline was increased by chronic BDL, but NAC preserved the normal hydroxyproline levels. Cytokines TGF-β, IL-6, and IL-10 increased after 28 days of BDL. NAC was effectively significant in preventing TGF-β and IL-6 expression and further augmented the IL-10 expression.
  
  
  CONCLUSIONS
  Our data indicate that in the development to cholestatic liver damage, oxidative stress plays an important role and this in turn leads to fibrosis. This study shows that the beneficial effects of NAC are because of its antioxidant and immunomodulatory properties.
authors.affiliation: Department of Pharmacology, CINVESTAV-IPN, Mexico, DF Mexico.
authors.forename: Marina
authors.initials: M
authors.lastname: Galicia-Moreno
authors.forename: Liliana
authors.initials: L
authors.lastname: Favari
authors.forename: Pablo
authors.initials: P
authors.lastname: Muriel
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002374:Catalase / Q000378:metabolism; D002779:Cholestasis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005355:Fibrosis / Q000517:prevention & control; D005978:Glutathione / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D016207:Cytokines; D018836:Inflammation Mediators; D002374:Catalase; D000410:Alanine Transaminase; D005978:Glutathione; D000111:Acetylcysteine