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

Toxicol Mech Methods. 2019 Feb;29(2):75-85. doi: 10.1080/15376516.2018.1512181. Epub 2018 Nov 29.

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: 1H-RMN; Experimental pulmonary fibrosis; aerosol; bleomycin; evolution; metabonomic.

Publication types

  • Comparative Study

MeSH terms

  • Aerosols
  • Animals
  • Antioxidants / metabolism
  • Biomarkers / metabolism
  • Bleomycin*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Disease Models, Animal
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Inhalation Exposure*
  • Lipid Peroxidation
  • Lung / metabolism*
  • Lung / pathology
  • Male
  • Metabolomics / methods
  • Oxidative Stress*
  • Proton Magnetic Resonance Spectroscopy
  • Pulmonary Fibrosis / chemically induced*
  • Pulmonary Fibrosis / metabolism
  • Pulmonary Fibrosis / pathology
  • Pulmonary Fibrosis / urine
  • Rats, Wistar
  • Time Factors
  • Transforming Growth Factor beta / metabolism

Substances

  • Aerosols
  • Antioxidants
  • Biomarkers
  • Transforming Growth Factor beta
  • Bleomycin