title: Influence of block of NF-kappa B signaling pathway on oxidative stress in the liver homogenates.
abstract: The aim of the present study was to assess whether BAY 11-7082, a nuclear factor-kappaB (NF- κ B) inhibitor, influences the level of reactive oxygen species (ROS), tumor necrosis factor alpha (TNF- α), and NF- κ B related signaling pathways in the liver. The animals were divided into 4 groups: I: saline; II: saline + endothelin-1 (ET-1) (1.25 μg/kg b.w., i.v.); III: saline + ET-1 (12.5 μg/kg b.w., i.v.); and IV: BAY 11-7082 (10 mg/kg b.w., i.v.) + ET-1 (12.5 μg/kg b.w., i.v.). Injection of ET-1 alone at a dose of 12.5 μg/kg b.w. showed a significant (P < 0.001) increase in thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) level and decrease (P < 0.01) in GSH level (vs. control). ET-1 administration slightly downregulated gene expression of p65 of NF- κ B but potently and in a dose-dependent way downregulated p21-cip gene expression in the liver. BAY 11-7082 significantly decreased TBARS (P < 0.001), H2O2 (P < 0.01) and improved the redox status (P < 0.05), compared to ET-1 group. The concentration of TNF- α was increased in the presence of ET-1 (P < 0.05), while BAY 11-7082 decreased TNF- α concentration (P < 0.01). Inhibition of IkB α before ET-1 administration downregulated gene expression of p21-cip but had no effect on p65.
authors.affiliation: Experimental and Clinical Physiology, Department of Cardiovascular Physiology, Medical University of Lodz, Lodz, Poland. kleniewska.p@interia.pl
authors.forename: Paulina
authors.initials: P
authors.lastname: Kleniewska
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Piechota-Polanczyk
authors.forename: Lukasz
authors.initials: L
authors.lastname: Michalski
authors.forename: Marta
authors.initials: M
authors.lastname: Michalska
authors.forename: Ewa
authors.initials: E
authors.lastname: Balcerczak
authors.forename: Marta
authors.initials: M
authors.lastname: Zebrowska
authors.forename: Anna
authors.initials: A
authors.lastname: Goraca
mesh_terms: D000818:Animals; D015536:Down-Regulation; D019332:Endothelin-1 / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013450:Sulfones / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D019332:Endothelin-1; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D009570:Nitriles; D017382:Reactive Oxygen Species; D013450:Sulfones; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D005978:Glutathione