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

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.

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.

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.

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.