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

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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.

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Authors and Affiliations

  1. Department of Physiology, University of León, 24071, León, Spain

    B. San-Miguel, J. González-Gallego & M. J. Tuñón

  2. Department of Animal Health, University of León, León, Spain

    M. Alvarez

  3. Hospital of León, León, Spain

    J. M. Culebras

Authors
  1. B. San-Miguel
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  2. M. Alvarez
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  3. J. M. Culebras
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  4. J. González-Gallego
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  5. M. J. Tuñón
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Correspondence to M. J. Tuñón.

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San-Miguel, B., Alvarez, M., Culebras, J.M. et al. N-acetyl-cysteine protects liver from apoptotic death in an animal model of fulminant hepatic failure. Apoptosis 11, 1945–1957 (2006). https://doi.org/10.1007/s10495-006-0090-0

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