Acute Pulmonary Toxicity Caused by Single Intratracheal Instillation of Various Doses of Colloidal Silver Nanoparticles in Mice: Pathological Changes, Particle Bioaccumulation and Metallothionien Protein Expression

To study acute lung toxicity of various doses of colloidal silver nanoparticles (Ag-NPs), mice were intratracheally instilled with 0, 10, 100, 1000 or 10,000 ppm of Ag-NPs. Histopathology, autometallography (AMG) and immunohistochemistry were determined at 1, 3, 7 and 15 days post-exposure.Instillation of 100, 1,000 and 10,000 ppm Ag-NPs produced moderate to severe necrotizing bronchitis and alveolitis with hypertrophy and hyperplasia of alveolar epithelial cells. The severity of the pulmonary inflammation and damage increased in a dose-dependent manner. Concomitant lamininimmunohistochemical findings generally correlated with pulmonary lesions. Interleukin 1-beta (IL-1 beta) and tumor necrotic factor-alpha (TNF-alpha) positive immunostaining were found in the inflammatory lesions in lungs of treated animals. Superoxide dismutase (SOD) and metallothionine (MT) expression occurred in particle laden AMs and lung epithelial cells, which correlated with inflammatory sites and particle aggregated areas. AMG gains were found inparticle laden AMs, alveolar epithelial cells and macrophages in hilarlymph nodes. These findings suggest that instillation of AgNPs causes acute lung inflammation and tissue damage in a concentration-dependent manner. IL-1 beta and TNF-alpha may involve in the pathogenesis of the acute lung toxicity. Oxidative stress may underlie the lung tissue injury. Moreover, the expression of MT in tissues responded to AgNPs accumulation.