title: Influence of nuclear factor-κB inhibition on endothelin-1 induced lung edema and oxidative stress in rats.
abstract: 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.
authors.affiliation: Chair of Experimental and Clinical Physiology, Department of Cardiovascular Physiology, Medical University of Lodz, Lodz, Poland. piechota.aleksandra@wp.pl
authors.forename: A
authors.initials: A
authors.lastname: Piechota
authors.forename: A
authors.initials: A
authors.lastname: Goraca
mesh_terms: D000818:Animals; D019332:Endothelin-1 / Q000633:toxicity*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D019332:Endothelin-1; D016328:NF-kappa B; D009570:Nitriles; D017382:Reactive Oxygen Species; D013450:Sulfones