Journal of Hepatology
Volume 49, Issue 1 , Pages 25-33, July 2008

Effects of N-acetylcysteine administration in hepatic microcirculation of rats with biliary cirrhosis☆

  • Ying-Ying Yang

      Affiliations

    • Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital Taipei, Taiwan
    • Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
    • ,
  • Kuei-Chuan Lee

      Affiliations

    • Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
    • Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei 11217, Taiwan
    • ,
  • Yi-Tsau Huang

      Affiliations

    • Institute of Traditional Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
    • ,
  • Ying-Wen Wang

      Affiliations

    • Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
    • Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei 11217, Taiwan
    • ,
  • Ming-Chih Hou

      Affiliations

    • Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
    • Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei 11217, Taiwan
    • ,
  • Fa-Yauh Lee

      Affiliations

    • Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital Taipei, Taiwan
    • Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
    • ,
  • Han-Chieh Lin

      Affiliations

    • Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
    • Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei 11217, Taiwan
    • Corresponding Author InformationCorresponding author. Fax: +886 2 28739318.
    • ,
  • Shou-Dong Lee

      Affiliations

    • Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
    • Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei 11217, Taiwan

Received 19 May 2007; received in revised form 16 January 2008; accepted 6 February 2008. published online 14 March 2008.

Associate Editor: J. Bosch

Background/Aims

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 A2 (TXA2) 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 TXA2 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.

Keywords: Anti-oxidants, Intrahepatic resistance, N-Acetylcysteine, Nitrotyrosilation

Abbreviations: NAC, N-acetylcysteine, TXS, thromboxane synthase, MnSOD, manganese superoxide dismutase, TXA2, thromboxane A2, NO, nitric oxide, GSH, Glutathione, GPx, GSH peroxidase, BDL, Bile-duct-ligation

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☆ The authors who have taken part in the research of this paper declared that they do not have a relationship with the manufacturers of the materials involved either in the past or present and they did not receive funding from the manufacturers to carry out their research.

PII: S0168-8278(08)00163-3

doi:10.1016/j.jhep.2008.02.012

Journal of Hepatology
Volume 49, Issue 1 , Pages 25-33, July 2008

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