Influence of nuclear factor-κB inhibition on endothelin-1 induced lung edema and oxidative stress in rats.

The aim of the present study is to determine the effects of the BAY 11-7082, a nuclear factor-kappaB (NF-κB) inhibitor, on endothelin-1 (ET-1) induced lung edema, the level of reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-α) in the lungs. Experiments were carried out on adult male Wistar-Kyoto rats. The animals were divided into 4 groups: Group I: saline-treated control; Group II: saline followed by ET-1 (12.5 μg/kg b.w., i.v.); Group III: BAY 11-7082 (10 mg/kg b.w., i.v.) administered one hour before saline; Group IV: BAY 11-7082 (10 mg/kg b.w., i.v.) administered 1 hour before ET-1 (12.5 μg/kg b.w., i.v.). Injection of ET-1 alone showed a significant (P<0.001) increase in thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H(2)O(2)) level as well as a decrease (P<0.01) in GSH level and GSH/GSSG ratio (P<0.02). BAY 11-7082 significantly decreased TBARS (P<0.01) and H(2)O(2) (P<0.05) level as well as improved the redox status (P<0.02) in the lungs. BAY 11-7082 also prevented ET-1 induced lung edema (P<0.05). The concentration of TNF-α (P<0.02) and p65 subunit of NF-κB signaling compound (P<0.001) was increased in the presence of ET-1, while BAY 11-7082 decreased both TNF-α level (P<0.05) and p65 subunit concentration (P<0.01). Our results indicate that BAY 11-7082 plays a protective role in ET-1 induced oxidative lung injury. It successfully prevents lung edema as well as ROS and TNF-α overproduction. Our results also highlight the important role of the NF-κB pathway in ET-1 induced lung injury and ROS overproduction.