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

Hyeon-Young Kim,Kyuhong Lee,Doin Joen,Min-Seok Kim,Sung-Hwan Kim

doi:10.3390/molecules23081974

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.

Highlights

Idiopathic pulmonary fibrosis (IPF) is a severely debilitating and fatal lung disease, with median survival ranging from two to three years after diagnosis [1,2,3]
The results of this study showed that NDN inhibits the inflammatory response and the NLRP3 inflammasome activation of lung fibrosis induced by PHMG
We evaluated the effects of NDN on PHMG-induced pulmonary injury in mice

Summary

Introduction

Idiopathic pulmonary fibrosis (IPF) is a severely debilitating and fatal lung disease, with median survival ranging from two to three years after diagnosis [1,2,3]. It is characterized by lung damage with a loss of alveolar epithelial cells and abnormal tissue repair, accumulation of abnormal fibroblasts and myofibroblasts, deposition of extracellular matrix, and distortion of pulmonary architecture, which result in respiratory failure [4,5]. In 2011, the Korea Centers for Disease Control and Prevention reported that fatal pulmonary disease may be caused by household humidifier disinfectants.

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