Majano Pedro Lorenzo, Medina Jesús, Zubía Itxaso, Sunyer Lourdes, Lara-Pezzi Enrique, Maldonado-Rodríguez Alejandra, López-Cabrera Manuel, Moreno-Otero Ricardo
Unidad de Hepatología (planta 3), Hospital Universitario de la Princesa, Universidad Autónoma, Diego de León 62, E-28006 Madrid, Spain.
J Hepatol. 2004 Apr;40(4):632-7. doi: 10.1016/j.jhep.2003.12.009.
BACKGROUND/AIMS: A major role has been described for inducible nitric oxide (NO) synthase in several chronic inflammatory liver diseases. N-Acetyl-cysteine (NAC) is a sulfhydryl donor molecule with antioxidant and antiinflammatory effects. It attenuates NO generation following lipopolysaccharide injection in rats. Our goal was to study the effect of NAC on NO synthase induction in hepatocytes in response to proinflammatory cytokines.
The effect of NAC on NO synthase induction was studied in the human hepatocyte cell lines HepG2 and 2.2.15 treated with a mixture of proinflammatory cytokines. Interactions between NAC and cytokines on nuclear factor-kappaB (NF-kappaB) activation and NO synthase promoter transactivation were investigated.
NAC dose-dependently modulated the induction of NO synthase mRNA expression, the release of nitrites and the formation of NF-kappaB binding complexes in cytokine-treated hepatocytes. NAC also reduced the transactivation of the NO synthase promoter.
Our data show that exposure of hepatocytes to NAC modulated NO synthase expression and NF-kappaB activity, the key responses of the hepatocyte to inflammatory mediators. These data constitute preliminary evidence that NAC might have hepatoprotective actions of potential relevance in chronic inflammatory liver diseases, mediated partially through the modulation of NO production.
背景/目的：诱导型一氧化氮合酶在几种慢性炎症性肝病中发挥了主要作用。N-乙酰半胱氨酸（NAC）是一种具有抗氧化和抗炎作用的巯基供体分子。它能减轻大鼠注射脂多糖后一氧化氮的生成。我们的目标是研究NAC对肝细胞中促炎细胞因子诱导的一氧化氮合酶的影响。
在用人促炎细胞因子混合物处理的人肝细胞系HepG2和2.2.15中研究NAC对一氧化氮合酶诱导的影响。研究了NAC与细胞因子之间对核因子-κB（NF-κB）激活和一氧化氮合酶启动子反式激活的相互作用。
NAC剂量依赖性地调节细胞因子处理的肝细胞中一氧化氮合酶mRNA表达的诱导、亚硝酸盐的释放以及NF-κB结合复合物的形成。NAC还降低了一氧化氮合酶启动子的反式激活。
我们的数据表明，肝细胞暴露于NAC可调节一氧化氮合酶表达和NF-κB活性，这是肝细胞对炎症介质的关键反应。这些数据构成了初步证据，表明NAC可能在慢性炎症性肝病中具有潜在的肝保护作用，部分是通过调节一氧化氮的产生介导的。
