Effect of cellular growth factors on hepatocytes in experimental infection--regulation of NF-kappa B and glutathione homeostasis]

Infections, sepsis and trauma lead to cellular damage of different degrees. The formation of nitrogen and reactive oxygen intermediates (NOI and ROI) play a central role in cellular damage. In addition, it is well established that the intracellular GSH content can control both radical species whereas GSH levels are controlled by the presence of cellular growth factors. The aim of the following study was to investigate the ROI and nitric oxide formation depending on the GSH levels and the presence or absence of hepatocellular growth factors. In addition, we investigated their effects on hepatocellular injury and the status of activation of the nuclear transcriptional factor NF-kappa B which is influenced by various radical forms and the cellular GSH contents. Our data clearly demonstrate that hepatocellular growth factors such as EGF and TGF alpha can increase the GSH contents and the NOx production. In addition, we found a reduction of cellular injury and NF-kappa B expression when hepatocytes were preincubated with growth factors. Taken together, we conclude that growth factors are able to protect against hepatocellular injury in experimental sepsis by increasing the cellular GSH contents either to reduce superoxide anion formation or to induce increased NO synthesis activity with subsequent increased NO production.