N-acetylcysteine attenuates lipopolysaccharide-induced apoptotic liver damage in d-galactosamine-sensitized mice

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-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

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Oxide_ 2001; 5: 349–60. Article  CAS  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Toxicology, Anhui Medical University, Hefei, 230032,

China Hua Wang, De-xiang Xu, Jin-wei Lu, Lei Zhao & Cheng Zhang * Institute of Clinical Pharmacology, Anhui Medical University, Hefei, 230032, China De-xiang Xu & Wei Wei Authors *

Hua Wang View author publications You can also search for this author inPubMed Google Scholar * De-xiang Xu View author publications You can also search for this author inPubMed Google

Scholar * Jin-wei Lu View author publications You can also search for this author inPubMed Google Scholar * Lei Zhao View author publications You can also search for this author inPubMed 

Google Scholar * Cheng Zhang View author publications You can also search for this author inPubMed Google Scholar * Wei Wei View author publications You can also search for this author

inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to De-xiang Xu. ADDITIONAL INFORMATION This project was supported by grants from the National Natural Science Foundation of China

(No 30371667, 30572223, and 30671786). RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Wang, H., Xu, Dx., Lu, Jw. _et al._ _N_-Acetylcysteine attenuates

lipopolysaccharide-induced apoptotic liver damage in _D_-galactosamine-sensitized mice. _Acta Pharmacol Sin_ 28, 1803–1809 (2007). https://doi.org/10.1111/j.1745-7254.2007.00657.x Download

citation * Received: 08 February 2007 * Accepted: 10 May 2007 * Issue Date: 01 November 2007 * DOI: https://doi.org/10.1111/j.1745-7254.2007.00657.x SHARE THIS ARTICLE Anyone you share the

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Nature SharedIt content-sharing initiative KEYWORDS * _N_-acetylcysteine * lipopolysaccharide * apoptosis * liver injury * antioxidant