Protective Effects of Nintedanib against Polyhexamethylene Guanidine Phosphate-Induced Lung Fibrosis in Mice
Nintedanib (NDN), a tyrosine kinase inhibitor, has been shown to have anti-tumor, anti-inflammatory, and anti-fibrotic effects in several reports. We investigated the protective effects of NDN against polyhexamethylene guanidine phosphate (PHMG)-induced lung fibrosis in mice. The following three exp...
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MDPI AG
2018-08-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/23/8/1974 |
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| author | Hyeon-Young Kim Min-Seok Kim Sung-Hwan Kim Doin Joen Kyuhong Lee |
| author_facet | Hyeon-Young Kim Min-Seok Kim Sung-Hwan Kim Doin Joen Kyuhong Lee |
| author_sort | Hyeon-Young Kim |
| collection | DOAJ |
| description | Nintedanib (NDN), a tyrosine kinase inhibitor, has been shown to have anti-tumor, anti-inflammatory, and anti-fibrotic effects in several reports. We investigated the protective effects of NDN against polyhexamethylene guanidine phosphate (PHMG)-induced lung fibrosis in mice. The following three experimental groups were evaluated: (1) vehicle control; (2) PHMG (1.1 mg/kg); and (3) PHMG & NDN (60 mg/kg). PHMG induced pulmonary inflammation and fibrosis by intratracheal instillation in mice. In contrast, NDN treatment effectively alleviated the PHMG induced lung injury, and attenuated the number of total cells and inflammatory cells in the bronchoalveolar lavage fluid, including the fibrotic histopathological changes, and also reduced the hydroxyproline content. NDN also significantly decreased the expression of inflammatory cytokines and fibrotic factors, and the activation of the NLRP3 inflammasome in lung tissues. These results suggest that NDN may mitigate the inflammatory response and development of pulmonary fibrosis in the lungs of mice treated with PHMG. |
| first_indexed | 2024-12-21T21:54:55Z |
| format | Article |
| id | doaj.art-f91af74939974a02918b79458cc686fc |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-21T21:54:55Z |
| publishDate | 2018-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-f91af74939974a02918b79458cc686fc2022-12-21T18:48:59ZengMDPI AGMolecules1420-30492018-08-01238197410.3390/molecules23081974molecules23081974Protective Effects of Nintedanib against Polyhexamethylene Guanidine Phosphate-Induced Lung Fibrosis in MiceHyeon-Young Kim0Min-Seok Kim1Sung-Hwan Kim2Doin Joen3Kyuhong Lee4National Center for Efficacy Evaluation of Respiratory Disease Product, Korea Institute of Toxicology, 30, Baekhak 1-gil, Jeongeup-si 56212, KoreaLaboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 360-4, KoreaNational Center for Efficacy Evaluation of Respiratory Disease Product, Korea Institute of Toxicology, 30, Baekhak 1-gil, Jeongeup-si 56212, KoreaNational Center for Efficacy Evaluation of Respiratory Disease Product, Korea Institute of Toxicology, 30, Baekhak 1-gil, Jeongeup-si 56212, KoreaNational Center for Efficacy Evaluation of Respiratory Disease Product, Korea Institute of Toxicology, 30, Baekhak 1-gil, Jeongeup-si 56212, KoreaNintedanib (NDN), a tyrosine kinase inhibitor, has been shown to have anti-tumor, anti-inflammatory, and anti-fibrotic effects in several reports. We investigated the protective effects of NDN against polyhexamethylene guanidine phosphate (PHMG)-induced lung fibrosis in mice. The following three experimental groups were evaluated: (1) vehicle control; (2) PHMG (1.1 mg/kg); and (3) PHMG & NDN (60 mg/kg). PHMG induced pulmonary inflammation and fibrosis by intratracheal instillation in mice. In contrast, NDN treatment effectively alleviated the PHMG induced lung injury, and attenuated the number of total cells and inflammatory cells in the bronchoalveolar lavage fluid, including the fibrotic histopathological changes, and also reduced the hydroxyproline content. NDN also significantly decreased the expression of inflammatory cytokines and fibrotic factors, and the activation of the NLRP3 inflammasome in lung tissues. These results suggest that NDN may mitigate the inflammatory response and development of pulmonary fibrosis in the lungs of mice treated with PHMG.http://www.mdpi.com/1420-3049/23/8/1974nintedanibpolyhexamethylene guanidine phosphatepulmonary fibrosisanti-fibrosisinflammasome |
| spellingShingle | Hyeon-Young Kim Min-Seok Kim Sung-Hwan Kim Doin Joen Kyuhong Lee Protective Effects of Nintedanib against Polyhexamethylene Guanidine Phosphate-Induced Lung Fibrosis in Mice Molecules nintedanib polyhexamethylene guanidine phosphate pulmonary fibrosis anti-fibrosis inflammasome |
| title | Protective Effects of Nintedanib against Polyhexamethylene Guanidine Phosphate-Induced Lung Fibrosis in Mice |
| title_full | Protective Effects of Nintedanib against Polyhexamethylene Guanidine Phosphate-Induced Lung Fibrosis in Mice |
| title_fullStr | Protective Effects of Nintedanib against Polyhexamethylene Guanidine Phosphate-Induced Lung Fibrosis in Mice |
| title_full_unstemmed | Protective Effects of Nintedanib against Polyhexamethylene Guanidine Phosphate-Induced Lung Fibrosis in Mice |
| title_short | Protective Effects of Nintedanib against Polyhexamethylene Guanidine Phosphate-Induced Lung Fibrosis in Mice |
| title_sort | protective effects of nintedanib against polyhexamethylene guanidine phosphate induced lung fibrosis in mice |
| topic | nintedanib polyhexamethylene guanidine phosphate pulmonary fibrosis anti-fibrosis inflammasome |
| url | http://www.mdpi.com/1420-3049/23/8/1974 |
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