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Molecules 2018, 23(8), 1974; https://doi.org/10.3390/molecules23081974

Protective Effects of Nintedanib against Polyhexamethylene Guanidine Phosphate-Induced Lung Fibrosis in Mice

1
National Center for Efficacy Evaluation of Respiratory Disease Product, Korea Institute of Toxicology, 30, Baekhak 1-gil, Jeongeup-si 56212, Korea
2
Department of Toxicology Evaluation, Graduate School of Pre-Clinical Laboratory Science, Konyang University, Daejeon 35365, Korea
3
Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 360-4, Korea
4
Department of Human and Environmental Toxicology, University of Science & Technology, Daejeon 34113, Korea
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Wai Shiu Fred Wong
Received: 26 June 2018 / Revised: 19 July 2018 / Accepted: 6 August 2018 / Published: 7 August 2018
(This article belongs to the Section Medicinal Chemistry)
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Abstract

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. View Full-Text
Keywords: nintedanib; polyhexamethylene guanidine phosphate; pulmonary fibrosis; anti-fibrosis; inflammasome nintedanib; polyhexamethylene guanidine phosphate; pulmonary fibrosis; anti-fibrosis; inflammasome
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Kim, H.-Y.; Kim, M.-S.; Kim, S.-H.; Joen, D.; Lee, K. Protective Effects of Nintedanib against Polyhexamethylene Guanidine Phosphate-Induced Lung Fibrosis in Mice. Molecules 2018, 23, 1974.

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