Open AccessN ‐Acetylcysteine attenuates lipopolysaccharide‐induced apoptotic liver damage in D ‐galactosamine‐sensitized mice 1
Author(s) -
WANG Hua,
XU Dexiang,
LU Jinwei,
ZHAO Lei,
ZHANG Cheng,
WEI Wei
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2007.00657.x
Subject(s) - acetylcysteine , pharmacology , glutathione , apoptosis , liver injury , chemistry , galactosamine , lipopolysaccharide , reactive oxygen species , nitric oxide , oxidative stress , buthionine sulfoximine , antioxidant , biochemistry , endocrinology , biology , enzyme , organic chemistry , glucosamine
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‐α is the major mediator leading to apoptotic liver injury. Reactive oxygen species (ROS) are involved in GalN‐induced sensitization to TNF‐α‐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‐α 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.