Inefficacy of dexamethasone and pirfenidone as comparators in the bleomycin-induced pulmonary fibrosis model in SD rats.

BACKGROUND

Pulmonary fibrosis (PF) is a severe disease leading to disability and death. It is important to search for novel therapeutic agents, for which a model of bleomycin-induced PF is used and pirfenidone and dexamethasone are used as comparators. The aim of the study was to establish the effect of comparators on model PF.

METHODS

We induced PF in male SD rats by intratracheal administration of 2.5 mg/kg bleomycin (BLM). Dexamethasone was administered intravenously (0.5 mg/kg, 7 days,), and pirfenidone was administered orally (50 mg/kg, 21 day). Clinical signs of health deviations, body weight, weight gain, food consumption and spirometry were monitored. The lung condition, cellular composition of the bronchoalveolar fluid (BALF), the lung concentration of hydroxyproline, blood biochemistry and the severity of fibrosis were analyzed 8 and 22 days post PF induction.

RESULTS

All animals administered BLM intratracheally developed pronounced signs of PF, including weight loss leading to pulmonary cachexia, deterioration in general condition, increased respiratory rate and decreased vital capacity, increased hydroxyproline levels in lung tissue, elevated level of neutrophils, lymphocytes, and pulmonary macrophages in the BALF. All of these features developed over time and were evident on day 8 and 22 of the study. Histological analysis revealed a pronounced inflammatory response on day 8 and a generalized fibrotic process on day 22. Dexamethasone and pirfenidone not only failed to improve clinical condition of animals, but even worsened it; one animal receiving pirfenidone died.

CONCLUSION

Animals with PF treated with dexamethasone and pirfenidone showed no improvement compared to untreated animals. Although dexamethasone reduced hydroxyproline levels, this did not improve either the animals' general condition or lung damage.