Influence of Block of NF-Kappa B Signaling Pathway on Oxidative Stress in the Liver Homogenates

The aim of the present study was to assess whether BAY 11-7082, a nuclear factor-kappaB (NF-kappa B) inhibitor, influences the level of reactive oxygen species (ROS), tumor necrosis factor alpha (TNF-alpha),and NF-kappa B related signaling pathways in the liver. The animals were divided into 4 groups: I: saline; II: saline + endothelin-1 (ET-1) (1.25.. g/kg b.w., i.v.); III: saline + ET-1 (12.5 mu g/kg b.w., i.v.); and IV: BAY 11-7082 (10 mg/kg b.w., i.v.) + ET-1 (12.5 mu g/kg b.w., i.v.). Injection of ET-1 alone at a dose of 12.5 mu g/kg b.w. showed a significant (P < 0.001) increase in thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) level and decrease (P < 0.01) in GSH level (vs. control). ET-1 administration slightly downregulated gene expression of p65 of NF-kappa B but potently and in a dose-dependent way downregulated p21-cip gene expression in the liver. BAY 11-7082 significantly decreased TBARS (P < 0.001), H2O2 (P < 0.01) and improved the redox status (P < 0.05), compared to ET-1 group. The concentration of TNF-.. was increased in the presence of ET-1 (P < 0.05), while BAY 11-7082 decreased TNF-alpha concentration (P < 0.01). Inhibition of IkB..before ET-1 administration downregulated gene expression of p21-cip but had no effect on p65.