title: Effect of a peroxynitrite scavenger, a manganese-porphyrin compound on airway remodeling in a murine asthma.
abstract: Airway remodeling, pathological changes in the lung structure, is a characteristic feature of chronic asthma. The changes include bronchial epithelial hyperplasia and hypertrophy, excess production of mucus, and fibroblast proliferation in the lung. On the other hand, it has been known that both nitric oxide and superoxide anion are increased in exhaled air of asthmatic patients. These molecules react with each other forming a powerful oxidant, peroxynitrite. In this study, effect of a peroxynitrite scavenger, a metalloporphyrin compound, [tetrakis(4-carboxylatophenyl)porphyrinato]manganese(III) (MnTBAP) on multiple antigen challenge-induced airway remodeling was evaluated in mice. When sensitized BALB/c mice were intratracheally challenged with an antigen, ovalbumin, for 3 times, bronchial epithelial thickening and mucus accumulation in the epithelium were histologically observed. Daily treatment with MnTBAP (3, 10 mg/kg/time/twice a day, intraperitoneally (i.p.)) dose-dependently suppressed both the epithelial thickening and mucus accumulation in the epithelium. On the other hand, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining revealed that the multiple antigen challenges increased the number of apoptotic cells in the bronchial epithelium. The increase in apoptotic cells was also effectively suppressed by the treatment with MnTBAP. Taken together, it was suggested that peroxynitrite could be involved in the formation of epithelial hyperplasia associated with the mucus accumulation through induction of apoptosis of the epithelial cells. Thus, peroxynitrite can be a target molecule for development of new pharmacotherapy for asthma.
authors: Department of Pharmacology, Kyoto Pharmaceutical University,Sakado, Saitama 350–0295, Japan.
authors: Yang
authors: Y
authors: Cao
authors: Masanori
authors: M
authors: Fujii
authors: Keiichi
authors: K
authors: Ishihara
authors: Satoshi
authors: S
authors: Akiba
authors: Hiroyuki
authors: H
authors: Yasui
authors: Takeshi
authors: T
authors: Nabe
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects* / Q000502:physiology; D000485:Allergens; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D007958:Leukocyte Count; D008665:Metalloporphyrins / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D030421:Peroxynitrous Acid / Q000378:metabolism*
chemical_list: D000485:Allergens; D016166:Free Radical Scavengers; D008665:Metalloporphyrins; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D030421:Peroxynitrous Acid; D010047:Ovalbumin