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Apoptosis

, Volume 11, Issue 11, pp 1945–1957 | Cite as

N-acetyl-cysteine protects liver from apoptotic death in an animal model of fulminant hepatic failure

  • B. San-Miguel
  • M. Alvarez
  • J. M. Culebras
  • J. González-Gallego
  • M. J. TuñónEmail author
Article

Abstract

Background: This work was undertaken to investigate whether treatment with N-acetyl-cysteine (NAC) prevents oxidative stress and inhibits the apoptotic pathways in an animal model of fulminant hepatic failure. Methods: Rabbits were experimentally infected with 2×104 hemagglutination units of a rabbit hemorrhagic disease virus isolate. Results: The spontaneous mortality rate of infected animals was 67% at 36 h post infection (pi) and 90% at 48 h pi. This percentage decreased significantly in animals receiving an i.p. injection of NAC (150 mg/kg body way/daily), for 7 days prior to infection. From 36 h pi marked increases were detected in blood levels of transaminases, lactate dehydrogenase, bilirubin and the oxidised/reduced glutathione ratio. All these effects were significantly prevented by NAC treatment. The Bax to Bcl-2 relative expression, the expression of FasL, cytochrome c and PARP-1, and the activity of caspase 3 were significantly increased at 36 and 48 h pi in infected animals. These changes were markedly reduced in animals treated with NAC, with the exception of FasL. Conclusion: Our results suggest a potential hepatoprotective role of NAC in fulminant hepatic failure, mediated partially through the modulation of the intrinsic pathway of apoptosis.

Keywords

Fulminant hepatic failure N-acetyl-cysteine Oxidative stress 

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Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • B. San-Miguel
    • 1
  • M. Alvarez
    • 2
  • J. M. Culebras
    • 3
  • J. González-Gallego
    • 1
  • M. J. Tuñón
    • 1
    Email author
  1. 1.Department of PhysiologyUniversity of LeónLeónSpain
  2. 2.Department of Animal HealthUniversity of LeónLeónSpain
  3. 3.Hospital of LeónLeónSpain

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