Nuclear factor kappa B inhibitor BAY 11-7082 suppresses oxidative stress induced by endothelin-1 (ET-1) in rat kidney

作者：Kowalczyk Agata^*; Kolodziejczyk Michal; Goraca Anna

来源：Postepy Higieny i Medycyny Doswiadczalnej, 2015, 69: 1512-1518.

• oxidative stress
• endothelin-1
• NF-kappa B
• p65 protein
• BAY 11-7082

Aim: The aim of the study was to evaluate the effect of BAY 11-7082, an NF-kappa B inhibitor, on basal and ET-1-induced production of reactive oxygen species (ROS), TNF-alpha and p65 protein in rat kidney.
Material/Methods: The experimental animals were divided into five groups (n=7) receiving: 1) saline (control); 2 and 3) ET-1 in a dose of 3 mu g/kg body weight (b.w.) or 12.5 mu g/kg b.w.; 4) BAY 11-7082 (10 mg/kg b.w.); 5) BAY 11-7082 (10 mg/kg b.w.) and ET-1 (12.5 mu g/kg b.w.), respectively. In kidney homogenates the concentration of thiobarbituric acid reactive substances (TBARS), H2O2, TNF-alpha, p65 protein and GSH/GSSG ratio were determined.
Results: ET-1 resulted in a dose-dependent increase in TBARS and hydrogen peroxide (H2O2) levels, and a decrease in GSH/GSSG ratio when compared to the controls. BAY 11-7082 administered 1 h before ET-1 administration at a dose of 12.5 mu g/kg resulted in a decrease (P<0.001) in TBARS and H2O2 levels and an increase (P<0.001) in GSH/GSSG ratio compared to the ET-1 groups. The level of TNF-alpha was increased (P<0.001) in the presence of ET-1, while BAY 11-7082 reduced the TNF-alpha level (P<0.001). The rats receiving BAY 11-7082 showed a decrease in NF-kappa B p65 protein level in the nuclear fraction and an increase in the cytoplasmic fraction.
Conclusions: The results suggest that BAY 11-7082 plays a protective role against ET-1 induced oxidative stress in kidney tissue. These actions of BAY 11-7082 may result from reduced activity of NF-kappa B signaling pathways. Inhibition of the NF-kappa B pathway may be a promising strategy for preventing the progression of kidney damage.

• 出版日期2015-12-31