title: Effects of N-acetylcysteine administration in hepatic microcirculation of rats with biliary cirrhosis.
abstract: OBJECTIVE
  Increased intrahepatic resistance (IHR) in cirrhosis is due to fibrosis and hepatic endothelial dysfunction (HED). Besides producing fibrosis, increased reactive oxygen species (ROS) promotes ROS-related nitration of anti-oxidative enzymes in cirrhotic livers. Tyrosine nitration (nitrotyrosilation)-related inactivation of anti-oxidative enzymes is increased in cirrhotic livers. This study investigates effects of N-acetylcysteine (NAC) administrations in bile-duct-ligation (BDL) rats.
  
  
  METHODS
  This study measured portal venous pressure (PVP), IHR, hepatic endothelial function, hepatic levels of anti-oxidants and oxidants, type III procollagen (PIIIP), proteins expression of thromboxane synthase (TXS), nitrotyrosine, manganese superoxide dismutase (MnSOD), and hepatic NOx and thromboxane A(2) (TXA(2)) production in perfusates.
  
  
  RESULTS
  The improvement of HED was associated with decreased PVP and IHR, hepatic protein and mRNA levels of PIIIP, protein expression of TXS and nitrotyrosine, oxidants and production of TXA(2) in NAC-treated BDL rat livers. Conversely, hepatic NOx production, anti-oxidants, and protein expression of MnSOD were increased in NAC-treated BDL rat livers.
  
  
  CONCLUSIONS
  In NAC-treated cirrhotic rats, the decrease in IHR was mainly caused by its anti-oxidative effect-related prevention of hepatic fibrogenesis associated with the decrease of oxidants-related nitrotyrosilation and improvement of HED.
authors.affiliation: Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital Taipei, Taiwan.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Yang
authors.forename: Kuei-Chuan
authors.initials: KC
authors.lastname: Lee
authors.forename: Yi-Tsau
authors.initials: YT
authors.lastname: Huang
authors.forename: Ying-Wen
authors.initials: YW
authors.lastname: Wang
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Hou
authors.forename: Fa-Yauh
authors.initials: FY
authors.lastname: Lee
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Lin
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001652:Bile Ducts; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008026:Ligation; D008102:Liver Circulation / Q000187:drug effects*; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D016877:Oxidants / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011347:Procollagen / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D016877:Oxidants; D010446:Peptide Fragments; D011347:Procollagen; D012333:RNA, Messenger; C041876:procollagen Type III-N-terminal peptide; C002744:3-nitrotyrosine; D014443:Tyrosine; D013482:Superoxide Dismutase; D013930:Thromboxane-A Synthase; D000111:Acetylcysteine