Effect of a Peroxynitrite Scavenger, a Manganese-Porphyrin Compound on Airway Remodeling in a Murine Asthma
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- Cao Yang
- Department of Pharmacology, Kyoto Pharmaceutical University
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- Fujii Masanori
- Department of Pharmacology, Kyoto Pharmaceutical University
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- Ishihara Keiichi
- Department of Pathological Biochemistry, Kyoto Pharmaceutical University
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- Akiba Satoshi
- Department of Pathological Biochemistry, Kyoto Pharmaceutical University
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- Yasui Hiroyuki
- Department of Analytical and Bioorganic Chemistry, Kyoto Pharmaceutical University
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- Nabe Takeshi
- Department of Pharmacology, Kyoto Pharmaceutical University
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抄録
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.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 36 (5), 850-855, 2013
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204634167680
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- NII論文ID
- 130003361429
- 40019637536
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC3svhtFKiug%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 024437052
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- PubMed
- 23439584
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- 抄録ライセンスフラグ
- 使用不可