Abstract | BACKGROUND: METHODS: Wild-type, single NOS knockout and triple NOS knockout (n/i/eNOS-/-) mice were administered bleomycin (BLM) intraperitoneally at a dose of 8.0 mg/kg/day for 10 consecutive days. Two weeks after the end of the procedure, the fibrotic and inflammatory changes of the lung were evaluated. In addition, we evaluated the effects of long-term treatment with isosorbide dinitrate, a NO donor, on the n/i/eNOS-/- mice with BLM-induced pulmonary fibrosis. RESULTS: The histopathological findings, collagen content and the total cell number in bronchoalveolar lavage fluid were the most severe/highest in the n/i/eNOS-/- mice. Long-term treatment with the supplemental NO donor in n/i/eNOS-/- mice significantly prevented the progression of the histopathological findings and the increase of the collagen content in the lungs. CONCLUSIONS: These results provide the first direct evidence that a lack of all three NOS isoforms led to a deterioration of pulmonary fibrosis in a BLM-treated murine model. We speculate that the entire endogenous NO and NOS system plays an important protective role in the pathogenesis of pulmonary fibrosis.
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Authors | Shingo Noguchi, Kazuhiro Yatera, Ke-Yong Wang, Keishi Oda, Kentarou Akata, Kei Yamasaki, Toshinori Kawanami, Hiroshi Ishimoto, Yumiko Toyohira, Hiroaki Shimokawa, Nobuyuki Yanagihara, Masato Tsutsui, Hiroshi Mukae |
Journal | Respiratory research
(Respir Res)
Vol. 15
Pg. 92
(Aug 05 2014)
ISSN: 1465-993X [Electronic] England |
PMID | 25092105
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Animals
- Bleomycin
(toxicity)
- Male
- Mice
- Mice, Knockout
- Nitric Oxide
(therapeutic use)
- Pulmonary Fibrosis
(chemically induced, pathology, prevention & control)
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