A comparative study of intratracheal and aerosolization instillations of bleomycin inducing experimental lung fibrosis in rat

Abstract

We aimed to investigate in the present work, using metabonomics approaches, the scalability of lung fibrosis-biomarkers, in bleomycin (BLM) model of pulmonary fibrosis in rats. Sixty male Wistar rats, weighing 250 ± 10 g, were randomly divided into three groups: a negative control group receiving normal saline treatment (G₁), an intratracheal BLM instilled group (G₂), and an aerosol BLM instilled group (G₃). Rats were investigated at various times after BLM instillation. Metabolic changes observed in different biofluids have been integrated into the results of the histological examination (increase in inflammation, fibrosis score, and TGF-β immunostaining) which provide a novel pathway of biomarkers in pulmonary fibrosis. These two BLM-models showed an efficacy in the production of pulmonary fibrosis in rats, accompanied by an oxidative stress in lung tissue as assessed by the increase of lipid peroxidation and the depletion in the level of antioxidant enzymes such as superoxide dismutase and catalase. The aerosol model was more advantageous showing fibrotic foci occupying the majority of the lung in contrast to intratracheal instillation characterized by a non-homogeneous distribution of the fibroblastic foci.

Keywords:

• Experimental pulmonary fibrosis
• evolution
• metabonomic
• 1H-RMN
• aerosol
• bleomycin

Acknowledgments

The authors are grateful to all persons who helped to conduct this study especially Alexandre ROOBE.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The present study was funded by the Tunisian Ministry of Higher Education (Tunis, Tunisia) and the Faculty of Medicine of Mons (Mons, Belgium).