# Pulmonary injury following exposure to amorphous silicon dioxide nanoparticles in Golden Syrian Hamsters

## TL;DR

Exposure to amorphous silicon dioxide nanoparticles in hamsters causes lung injury and inflammation, with higher concentrations leading to more severe effects.

## Contribution

This study demonstrates that high concentrations of amorphous SiO2 NPs induce pulmonary injury via the extrinsic apoptotic pathway in vivo.

## Key findings

- High concentration SiO2 NP exposure increased bronchoalveolar lavage fluid markers of inflammation and apoptosis.
- Histopathological analysis showed increased air space and TUNEL-positive cells in the high concentration group.
- Structural lung alterations and elevated caspase and inflammation markers confirm extrinsic apoptotic pathway activation.

## Abstract

Amorphous silicon dioxide nanoparticles (SiO2 NPs) are abundant within the earth’s crust and can be released into the air through industrial and manufacturing activities. Such materials are often used in industrial processes, in pharmaceutical and in the cosmetic industries. Amorphous SiO2 NPs are pulmonary toxicants; however, the mechanism of toxicity is uncertain. In the current study, toxicity of SiO2 NPs was assessed using inhalation exposure in an in vivo system to study a possible mechanism of pulmonary injury. Golden Syrian Hamsters were divided into 4 groups: 1- room air control, 2- vehicle control, 3- low concentration (6 mg/m3) and 4- high concentration (12 mg/m3). Hamsters were treated for 4 h a day for 8 days. Bronchoalveolar Lavage Fluid (BALF) analysis found increases in total cell counts (p < 0.0001), neutrophils (p < 0.0001), lymphocytes (p < 0.001), eosinophils (p < 0.01), multinucleated macrophages (p < 0.01), total protein (p < 0.0001), alkaline phosphatase (p < 0.0001), and lactate dehydrogenase (p < 0.001) in the high concentration group. Histopathological analysis found an increase in air space, quantified by Mean Linear Intercept (p < 0.0001), and a significant increase in TUNEL positive cells (p < 0.001), in the high concentration group. SEM and TEM found structural alterations to the lung tissue including increase in the number holes in the alveolar walls and in apoptotic bodies within tissue. Caspase 3 (p < 0.05), and 8 (p < 0.05), were significantly increased along with cellular inflammation markers TNF-α (p < 0.05), and HSP70 (p < 0.05) in the high concentration group. Results of the study indicate exposure to SiO2 NPs may induce extrinsic apoptotic pathway, leading to tissue damage and significant airspace enlargement.