N-acetyl-cysteine protects liver from apoptotic death in an animal model of fulminant hepatic failure.
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 2x10(4) 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.


CONCLUSIONS
Our results suggest a potential hepatoprotective role of NAC in fulminant hepatic failure, mediated partially through the modulation of the intrinsic pathway of apoptosis.
San-Miguel
B
B
Department of Physiology, University of León, 24071, León, Spain.
Alvarez
M
M
Culebras
J M
JM
González-Gallego
J
J
Tuñón
M J
MJ
D000111:Acetylcysteine / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D017849:Animals, Inbred Strains; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis; D017250:Caliciviridae Infections / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D017929:Hemorrhagic Disease Virus, Rabbit / Q000502:physiology; D022781:Hepatocytes / Q000473:pathology* / Q000821:virology; D008099:Liver / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D017114:Liver Failure, Acute / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D011817:Rabbits
D000975:Antioxidants; D000111:Acetylcysteine