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 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.