Pharmacological studies on pulmonary fibrosis model induced by intratracheal instillation of bleomycin in mice

Abstract

Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive interstitial lung diseases characterized by a chronic and progressive course leading to respiratory failure. The effects of nintedanib (NTB) and pirfenidone (PIR) on the changes in respiratory function, lung hydroxyproline (Hyp) levels, and lung tissue were examined with the pulmonary fibrosis model induced by bleomycin (BLM) in mice.

   BLM was intratracheally instilled once (Day 0), and NTB and PIR were orally administered daily from Day 7 to 20. In the pulmonary fibrosis model, increased specific airway resistances (sRaw) and decreased tidal volumes (TV) and peak expiratory flows (PEF) were observed from Day 6 to 21, and increased Hyp levels and infiltration of mononuclear cells and foamy macrophages (inflammation) and collagen fibers hyperplasia (fibrosis) in the lung were observed on Day 21. NTB and PIR suppressed the increase in sRaw and the decreases in TV and PEF on Days 14 and 21, and NTB also showed a tendency to inhibit histopathological changes such as inflammation and fibrosis in the lung.

   As described above, NTB and PIR improved respiratory failure induced by BLM, and NTB also showed a tendency to inhibit inflammation and fibrosis in the lung.

   This research was supported by AMED under Grant Number JP18nk0101402.