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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Anti-Asthmatic Agents, Asthma, Bronchial Hyperreactivity, Bronchoalveolar Lavage Fluid, Disease Models, Animal, Female, Glutathione, Glutathione Disulfide, Imidazoles, Lung, Mice, Mice, Inbred C57BL, Nitriles, Oligopeptides, Pyrimidines, Reactive Oxygen Species, Sulfhydryl Compounds, Sulfones, p38 Mitogen-Activated Protein Kinases.
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Does a novel dithiol amide CB3 attenuate allergic airway disease through negative regulation of p38 mitogen-activated protein kinase? Context: Cellular redox homeostasis altered by excessive production of reactive oxygen species (ROS) and weakening of the antioxidant defense leads to oxidative stress. Oxidative stress is characterized as a decrease in glutathione/glutathione disulfide (GSH/GSSG) and the triggering of a number of the redox-sensitive signaling cascades. Recent studies have demonstrated that ROS play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Here we characterized for the first time the protective properties of a new hydrophobic thiol compound, N-acetyl cysteine proline cysteine amide (CB3), in allergic airway diseases. We used ovalbumin (OVA)-inhaled mice to evaluate the role of CB3 as an antiinflammatory reagent and to determine its molecular signaling activity in allergic airways. The administration of CB3 (1-50 mg/kg) to OVA-inhaled mice restored the decreased GSH levels, enhanced IL-10 expression, and significantly reduced the increase of Th2 cytokines and OVA-specific IgE. CB3 decreased the number of inflammatory cells and airway hyperresponsiveness in the lungs. We also found that the administration of CB3 dramatically decreased the nuclear translocation of the nuclear factor-κB (NF-κB) and the phosphorylation of p38 mitogen-activated protein kinases (MAPKs) in lungs after OVA inhalation. In addition, allergen-induced airway inflammation and hyperresponsiveness were substantially reduced by the administration of inhibitors of NF-κB and p38 MAPK, BAY 11-7085, and SB 239063, respectively.
assistant
These results suggest that CB3 attenuates allergic airway disease by up-regulation of GSH levels as well as inhibition of NF-κB and p38 MAPK activity. Final Decision: yes