Abstract
Activation of Kupffer cells, the resident macrophage population of the liver, has been implicated in the pathogenesis of several types of liver injury. The aim of this study was to investigate whether the antioxidants N-acetylcysteine (NAC) and α-tocopherol succinate (α-TOC) suppress lipopolysaccharide (LPS)-induced activation of rat Kupffer cells. LPS activated NF-κB in Kupffer cells, and this response was inhibited by NAC and α-TOC. NAC and α-TOC also markedly suppressed LPSinduced tumor necrosis factor-α (TNF-α) mRNA levels and secretion. We further show that LPS was unable to increase TNF-α mRNA in drug-treated cells even when stimulation occurred after NAC or α-TOC were removed. These results indicate that antioxidants persistently suppress LPS activation in Kupffer cells, and suggest that the mechanism responsible for this involves more than mere quenching of free radical production. The demonstration that NAC and α-TOC have inhibitory effects on LPS-mediated Kupffer cell activation suggests that these compounds may have a beneficial effect in liver injury involving oxidative stress and endotoxemia.
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