Pathological Comparison of Rat Pulmonary Models Induced by Silica Nanoparticles and Indium-Tin Oxide Nanoparticles

Int J Nanomedicine. 2022 Sep 15:17:4277-4292. doi: 10.2147/IJN.S380259. eCollection 2022.

Abstract

Purpose: The objective of this study was to evaluate and compare the histopathological implications of silica nanoparticles (Nano-SiO2) and indium-tin oxide nanoparticles (Nano-ITO), in vivo.

Methods: Male Sprague-Dawley rats were exposed to Nano-SiO2 (50 mg/kg) and Nano-ITO (6 mg/kg) by a single intratracheal instillation, respectively. Broncho-alveolar lavage fluid (BALF) and lung tissue were obtained at 7, 14, 28, and 56 days post exposure for analysis of BALF inflammatory factors, total protein, and for lung tissue pathology. Histopathological and ultrastructural change in lungs were investigated by hematoxylin and eosin, Masson's trichrome, sirius red staining, periodic acid Schiff stain, and transmission electron microscopy. The expression of SP-A, collagen type I and III in lung tissue was determined by immunohistochemistry and ELISA.

Results: The rats in both models exhibited obvious collagen fibrosis and the severity of the lung injury increased with time after exposure to respective dosage increased. Several parameters of pulmonary inflammation and fibrosis significantly increased in both groups, which was reflected by increased LDH activity, total proteins, TNF-α, and IL-6 levels in BALF, and confirmed by histopathological examination. The results also showed that the two models exhibited different features. Exposure to Nano-ITO caused persistent chronic lung inflammation, illustrated by the infiltration of a large amount of enlarged and foamy macrophages and neutrophils into the lung parenchyma. In Nano-SiO2 exposed rat lung tissue, granulomatous inflammation was most prominent followed by progressive and massive fibrotic nodules. Compared with the Nano-SiO2 rats, Nano-ITO exposed rats exhibited significantly severe pulmonary alveolar proteinosis (PAP) pathological changes, lower fibrosis, and higher levels of inflammatory biomarkers. However, Nano-SiO2 exposed rats had greater fibrosis pathological changes and more severe granulomas than Nano-ITO exposed rats.

Conclusion: This study suggests that the Nano-SiO2-induced model has greater value in research into granulomas and fibrosis, while the Nano-ITO-induced model has greater repeatability in area of PAP.

Keywords: indium lung disease; indium-tin oxide nanoparticles; pulmonary alveolar proteinosis; silica nanoparticles; silicosis.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid
  • Collagen Type I / metabolism
  • Eosine Yellowish-(YS) / metabolism
  • Fibrosis
  • Hematoxylin / metabolism
  • Indium
  • Interleukin-6 / metabolism
  • Lung / pathology
  • Male
  • Metal Nanoparticles
  • Nanoparticles* / toxicity
  • Periodic Acid / metabolism
  • Pneumonia* / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Silicon Dioxide / toxicity
  • Tin Compounds
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Collagen Type I
  • Interleukin-6
  • Tin Compounds
  • Tumor Necrosis Factor-alpha
  • Indium
  • Periodic Acid
  • indium tin oxide
  • Silicon Dioxide
  • stannic oxide
  • Eosine Yellowish-(YS)
  • Hematoxylin

Grants and funding

This research was funded by the Basic Scientific Research Funds for Provincial Universities of North China University of Science and Technology [JQN2020013], grants from the National Natural Science Foundation of China ([U21A20334], and Graduate Innovation Project (No. 2019B17).