Journal of the Chinese Medical Association
Volume 70, Issue 1 , Pages 16-23, January 2007

Role of Hepatic Nitric Oxide Synthases in Rats with Thioacetamide-induced Acute Liver Failure and Encephalopathy

  • Hui-Chun Huang

      Affiliations

    • Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
    • ,
  • Sun-Sang Wang

      Affiliations

    • Taipei Municipal Gan-Dau Hospital, Taipei, Taiwan, R.O.C.
    • National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
    • ,
  • Cho-Yu Chan

      Affiliations

    • Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
    • ,
  • Yi-Chou Chen

      Affiliations

    • Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • ,
  • Fa-Yauh Lee

      Affiliations

    • Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
    • Corresponding Author InformationCorrespondence to: Dr Fa-Yauh Lee, Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan, R.O.C.
    • ,
  • Full-Young Chang

      Affiliations

    • Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
    • ,
  • Chi-Jen Chu

      Affiliations

    • Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
    • ,
  • Han-Chieh Lin

      Affiliations

    • Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
    • ,
  • Rei-Hwa Lu

      Affiliations

    • Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • ,
  • Shou-Dong Lee

      Affiliations

    • Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.

Received 17 July 2006; received in revised form 11 October 2006

Article Outline

Background

Hepatic encephalopathy is neuropsychiatric derangement secondary to hepatic decompensation or portal-systemic shunting. Nitric oxide (NO) synthase inhibition aggravates encephalopathy and increases mortality in rats with thioacetamide (TAA)-induced acute liver failure, suggesting a protective role of NO. This study investigated the roles of endothelium-derived constitutive NO synthase (eNOS) and inducible NOS (iNOS) in the liver of rats with fulminant hepatic failure and encephalopathy.

Methods

Male Sprague-Dawley rats (300-350 g) were randomized to receive TAA 350 mg/kg/day, by intraperitoneal injection or normal saline for 3 days. Severity of encephalopathy was assessed with the Opto-Varimex animal activity meter. Plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin were measured. Hepatic iNOS and eNOS RNA and protein expressions were assessed by reverse transcription-polymerase chain reaction and Western blot analyses, respectively.

Results

The TAA group showed lower motor activity counts than the normal saline group. Hepatic eNOS, but not iNOS, mRNA and protein expressions were enhanced in the TAA group. In addition, hepatic eNOS mRNA expression was negatively correlated with total movement but positively correlated with ALT and AST. Protein expression of hepatic eNOS was positively correlated with ALT, AST and bilirubin.

Conclusion

Upregulation of hepatic eNOS was observed in rats with TAA-induced fulminant hepatic failure and encephalopa-thy, which might play a regulatory role.

Key Words:  fulminant hepatic failure , hepatic encephalopathy , nitric oxide , nitric oxide synthase , thioacetamide

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PII: S1726-4901(09)70295-3

doi:10.1016/S1726-4901(09)70295-3

Journal of the Chinese Medical Association
Volume 70, Issue 1 , Pages 16-23, January 2007

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