Inhibition of airway inflammation and hyperreactivity by an antioxidant mimetic.
A catalytic antioxidant, AEOL 10113, was used in a murine model of asthma to test the hypothesis that oxidants contribute to the pathogenesis of asthma. Balb/c mice were immunized and challenged with ovalbumin. AEOL 10113 was administered to the mice by intratracheal instillation during ovalbumin challenges. Enhanced pause as an indicator of airway reactivity and differential cell count of lavage cells as an indicator of airway inflammation were assessed. Lung expressions of the adhesion molecules VCAM-1 and ICAM-1 were measured. We found that treatment of ovalbumin-challenged mice with AEOL 10113 drastically reduced the severity of airway inflammation as evidenced by the reduced numbers of eosinophils, neutrophils, and lymphocytes found in bronchoalveolar lavage fluid. Inhibition of ovalbumin-induced airway inflammation is associated with inhibited expression of VCAM-1, which is a key adhesion molecule responsible for the recruitment of inflammatory cells into the lungs of ovalbumin-challenged mice. In addition, treatment with AEOL 10113 reduced the magnitude of ovalbumin-induced airway hyperreactivity to methacholine. These results suggest that oxidative stress is an important factor in the pathogenesis of asthma and that a synthetic catalytic antioxidant could be effective in the treatment of asthma.
Division of Environmental and Occupational Health Sciences, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA. changl@njc.org
Ling-Yi
LY
Chang
James D
JD
Crapo
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000166:cytology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D008665:Metalloporphyrins / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000166:cytology; D010047:Ovalbumin / Q000633:toxicity; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000975:Antioxidants; D008665:Metalloporphyrins; D019010:Vascular Cell Adhesion Molecule-1; C431023:manganese (III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin; D018799:Intercellular Adhesion Molecule-1; D010047:Ovalbumin