Effect Of Thiol On LPS-induced Liver Injury

The intracellular reduction/oxidation(redox) state has been shown to affect signal transduction,regulate cellular function,such as viability, activation, immunity, inflammation. As the most abundant intracellular thio!,glutathione(GSH) plays a critical role as an intracellular redox buffer. Diethyl maleate(DEM),a thiol oxidant,can deplete intracellular GSH manipulate the intracellular redox state. LPS activate kupffer cells releasing excess reactive oxygen species result in oxidative stress which is the most important mechanism of liver injury induced by LPS.And oxidative stress can alter gene expression through activation nuclear factor B transduction pathway,leading to up-regulation of cytokines, cheinokines, adhesion molecules, FasL, or can induce permeability transition in mitochondria with cell apoptosis. However, much less is known about the effect of redox imbalance on LPS-induced liver injury in vivo. Using diethylmaleate(DEM) as a glutathione-depleting agent,we manipulate the intracellular redox state and clarify the role of redox state in the liver injury induced by LPS.Male mice were treated with LPS plus D-galactosamine(GaIn) develop liver injury,as evidenced by liver enzyme release,morphological changes, the exccnt of kupffer cells and oxidative stress.Pretreatment with DEMabrogate this injury and modulate nuclear factor-кB activity.Further work show DEM can affect the I K B degradation and nuclear factor- K B activity. We conclude that redox manipulation through thiol oxidation DEM may represent a novel approach to preventing LPS-induced liver injury by modulating kupffer'cells activity ,NF-к B transduction pathway .