Effects of silver nanoparticles-polysaccharide on bleomycin-induced pulmonary fibrosis in rats

J Pharm Pharmacol. 2021 Oct 7;73(11):1503-1512. doi: 10.1093/jpp/rgab037.

Abstract

Objectives: The first goal of this study was to synthesize the silver nanoparticles Alcaligenes xylosoxidans exopolysaccharide (Ag-AXEPS). The second objective was to analyse the role of Ag-AXEPS nanoparticles (NPS) in treating bleomycin (BLM)-induced lung fibrosis.

Methods: Intratracheal bleomycin (2.5 U/kg) was administered to prompt pulmonary fibrosis in rats, and pulmonary fibrosis was treated with Ag-AXEPS nanoparticles (100 ppm/twice a week for four weeks).

Key findings: Ag-AXEPS nanoparticles significantly decreased the diversity of pulmonary inflammatory agents in rats with BLM-induced fibrosis. Reduced levels of respiratory tumor necrosis factor-alpha, monocyte chemotactic protein-1, matrix metalloproteinases (MMP-2 and MMP-9) were observed on treatment with synthesized Ag-AXEPS. Similarly, the treatment decreased IL-12, mRNA levels of BAX and plasma fibrosis markers like N-terminal procollagen III propeptide and transforming growth factor-β1. On the other hand, the treatment increased mRNA BCL2 and total antioxidant capacity. It also lowered the level of fibrosis, as was shown by a quantified pathologic study of hematoxylin-eosin-stained lung parts. The treatment, however, ensured that lung collagen was restored, as assessed by Masson's trichrome stain, and that overall survival was increased and enhanced.

Conclusions: Our work showed that nanoparticles could be obtained at 37°C and may be a possible pulmonary fibrosis therapeutic agent.

Keywords: Masson’s trichrome; apoptosis; exopolysaccharides; matrix metalloproteinases; pulmonary fibrosis.

MeSH terms

  • Alcaligenes
  • Animals
  • Antibiotics, Antineoplastic / adverse effects*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Apoptosis
  • Bleomycin / adverse effects*
  • Collagen / metabolism
  • Fibrosis
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / prevention & control
  • Lung / drug effects*
  • Lung / pathology
  • Male
  • Matrix Metalloproteinases / metabolism
  • Metal Nanoparticles / therapeutic use
  • Nanoconjugates / therapeutic use
  • Nanoparticles / therapeutic use*
  • Pneumonia / chemically induced
  • Pneumonia / metabolism
  • Pneumonia / prevention & control
  • Polysaccharides / pharmacology
  • Polysaccharides / therapeutic use
  • Polysaccharides, Bacterial / pharmacology
  • Polysaccharides, Bacterial / therapeutic use*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / drug therapy*
  • Pulmonary Fibrosis / metabolism
  • Pulmonary Fibrosis / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Silver / pharmacology
  • Silver / therapeutic use*
  • Transforming Growth Factor beta1 / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antibiotics, Antineoplastic
  • Antioxidants
  • Nanoconjugates
  • Polysaccharides
  • Polysaccharides, Bacterial
  • Proto-Oncogene Proteins c-bcl-2
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • bcl-2-Associated X Protein
  • Bleomycin
  • Silver
  • Collagen
  • Matrix Metalloproteinases