Nuclear factor κB inhibitor BAY 11-7082 suppresses oxidative stress induced by endothelin-1 (ET-1) in rat kidney.
OBJECTIVE
The aim of the study was to evaluate the effect of BAY 11-7082, an NF-κB inhibitor, on basal and ET-1-induced production of reactive oxygen species (ROS), TNF-α and p65 protein in rat kidney.


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 μg/kg body weight (b.w.) or 12.5 μg/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 μg/kg b.w.), respectively. In kidney homogenates the concentration of thiobarbituric acid reactive substances (TBARS), H2O2, TNF-α, 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 μg/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-α was increased (P<0.001) in the presence of ET-1, while BAY 11-7082 reduced the TNF-α level (P<0.001). The rats receiving BAY 11-7082 showed a decrease in NF-κB 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-κB signaling pathways. Inhibition of the NF-κB pathway may be a promising strategy for preventing the progression of kidney damage.
Department of Cardiovascular Physiology, Chair of Experimental and Clinical Physiology, Medical University of Lodz, Poland.
Agata
A
Kowalczyk
Chair of Applied Pharmacy, Faculty of Pharmacy, Medical University of Lodz, Poland.
Michał
M
Kołodziejczyk
Department of Cardiovascular Physiology, Chair of Experimental and Clinical Physiology, Medical University of Lodz, Poland.
Anna
A
Gorąca
D000818:Animals; D019332:Endothelin-1 / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013450:Sulfones / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D019332:Endothelin-1; D016328:NF-kappa B; D009570:Nitriles; D017382:Reactive Oxygen Species; D013450:Sulfones; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide