Exiperimental Study Of N-acetylcysteine On Endotoxin-induced Liver Injury

Objective: Oxidative stress through Kupffer cells activation is one of an importantmechanisms that endotoxin induces liver injury. And Kupffer cells activation andits oxidative stress is closely relevant to the redox state of GSH. UsingN-acetylcysteine(NAC) as a glutathione-increasing agent, we manipulate theredox state of Kupffer's cells GSH in order to clarify the role of it in the liverinjury induced by LPS.Methods: Kunming rats, male, 25g, were randomized to live injurygroup(Galn/LPS,6mg/2 g, i.p.), to NAC group(pretreatment with NAC,700mg/Kg, i.g.) and control group. Six hours after Galn/LPS was administered,the parameters of serum ALT activity,MDA and GSH measured and historicalstaining of hepatic tissue was evaluated At the same time we determined theexpression of NF-кBp65 and CD68.Results: The animals,which were reated with Galn/LPS,develop liver injury, asevidenced by ALT activity, morphogical chages, the excent of Kupffer cells andoxidative stress. Compared with other groups, pretreatment with NAC abrogatethis injury and modulate nuclear factor-кB activity. Our study show: NAC candown-regulation of the NF-кB translocation.Concusion: Through producing amounts of the cellular GSH withN-acetylcysteine(NAC), we conclude that redox manipulation of Kupffer cellmay represent a new approach to preventing LPS induced liver injury bymodulating Kupffer's cells activity and NF-KB transduction pathway.