Influence of nuclear factor-κB inhibition on endothelin-1 induced lung edemaand 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 2o 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 2o 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.