Acute and Subacute Pulmonary Toxicity of Low Dose of Ultrafine Colloidal Silica Particles in Mice after Intratracheal Instillation

Abstract

To study the acute and subacute lung toxicity of low dose of ultrafine colloidal silica particles (UFCSs), mice were intratracheally instilled with 0, 0.3, 3, 10, 30 or 100 microg of UFCSs. Cellular and biochemical parameters in bronchoalveolar lavage fluid (BALF), histological alteration and the body weight were determined at 3 days after instillation. Exposure to 30 or 100 microg of UFCSs produced moderate to severe pulmonary inflammation and tissue injury. To investigate the time response, mice were instilled with 30 microg of UFCSs and sacrificed at intervals from 1 to 30 days post-exposure. UFCSs induced moderate pulmonary inflammation and injury on BALF indices at acute period; however, these changes gradually regressed until recovery during the experiment. Concomitant histopathological and laminin immunohistochemical findings generally correlated to BALF data. TUNEL analyses in UFCSs-treated animals showed a significant increase of the apoptotic index in lung parenchyma at all observation times. 8-OHdG expression occurred in lung epithelial cells and activated macrophages, which correlated to lung lesions in UFCSs-treated mice. These findings suggest that instillation of a small dose of UFCSs causes transient acute moderate lung inflammation and tissue damage. Oxidative stress and apoptosis may underlie the lung tissue injury induction.