N-Acetylcysteine attenuates lipopolysaccharide-induced apoptotic liver damage in D-galactosamine-sensitized mice  

作　　者：Hua WANG De-xiang XU Jin-wei LU Lei ZHAO Cheng ZHANG Wei WEI 

机构地区：[1]Department of Toxicology and Anhui Medical University, Hefei 230032, China [2]Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, China

出　　处：《Acta Pharmacologica Sinica》2007年第11期1803-1809,共7页中国药理学报（英文版）

基　　金：grants from the National Natural Science Foundation of China(№ 30371667,30572223,and 30671786)

摘　　要：Aim： To investigate the effects of N-acetylcysteine on D-galactosamine （GAIN）/ lipopolysaccharide （LPS）-induced apoptotic liver injury in mice. Methods： When given together with a low dose of LPS, GaIN 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 GaiN-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 GaiN-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 GaiN-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.Aim： To investigate the effects of N-acetylcysteine on D-galactosamine （GAIN）/ lipopolysaccharide （LPS）-induced apoptotic liver injury in mice. Methods： When given together with a low dose of LPS, GaIN 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 GaiN-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 GaiN-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 GaiN-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.

关 键 词：N-ACETYLCYSTEINE LIPOPOLYSACCHARIDE APOPTOSIS liver injury ANTIOXIDANT 

分 类 号：R575[医药卫生—消化系统]