N-acetylcysteine attenuates lipopolysaccharide-induced apoptotic liver damage in D-galactosamine-sensitized mice.
Acta Pharmacol Sin
; 28(11): 1803-9, 2007 Nov.
Article
en En
| MEDLINE
| ID: mdl-17959032
ABSTRACT
AIM:
To investigate the effects of N-acetylcysteine on D-galactosamine (GalN)/ lipopolysaccharide (LPS)-induced apoptotic liver injury in mice.METHODS:
When given together with a low dose of LPS, GalN highly sensitizes animals to produce apoptotic liver injury with severe hepatic congestion, resulting in rapid death. In the GalN/LPS model, TNF-alpha is the major mediator leading to apoptotic liver injury. Reactive oxygen species (ROS) are involved in GalN-induced sensitization to TNF-alpha-evoked hepatocyte apoptosis. N-acetylcysteine (NAC) is an antioxidant and a glutathione (GSH) precursor. In this study, we investigated the effects of NAC on LPS-induced apoptotic liver injury in GalN-sensitized mice.RESULTS:
Pretreatment with NAC significantly reduced GalN/LPS-induced elevation of serum alanine aminotransferase levels. In parallel, GalN/LPS-induced hepatic necrosis and congestion were obviously improved by NAC. Furthermore, NAC pretreatment significantly alleviated GalN/LPS-induced hepatic apoptosis, measured by the inhibition of hepatic caspase-3 activity and attenuation of DNA laddering. NAC pretreatment had no effect on LPS-evoked nitric oxide production in GalN-sensitized mice. Increases in serum TNF-alpha concentration, which were observed in GalN/LPS-treated mice, were not significantly reduced by NAC. Although NAC pretreatment significantly alleviated LPS-induced hepatic GSH depletion, DL-buthionine-(SR)-sulfoximine, an inhibitor of GSH synthesis, did not influence the protective effect of NAC on GalN/LPS-induced apoptotic liver injury.CONCLUSION:
NAC attenuates GalN/LPS-induced apoptotic liver injury via its strong ROS scavenging and anti-apoptotic effects.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Acetilcisteína
/
Apoptosis
/
Enfermedad Hepática Inducida por Sustancias y Drogas
/
Galactosamina
/
Antioxidantes
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Acta Pharmacol Sin
Asunto de la revista:
FARMACOLOGIA
Año:
2007
Tipo del documento:
Article
País de afiliación:
China