Pathological mechanisms of liver injury caused by continuous intraperitoneal injection of silica nanoparticles

Crystalline silica is well known to induce chronic lung inflammation by inhalation that can progress to silicosis. Recently, we reported that silica nanoparticles (SN) cause more damage to liver instead of lung when they enter the body by intravenous injection. However, this mechanism is still unclear. In the present study, liver damages caused by mesoporous hollow silica nanoparticles (MHSNs) were demonstrated after continuous intraperitoneal injection into mice twice a week for 6 weeks. The administration of MHSNs at 50 mg/kg increased liver injury markers in serum, such as alanine aminotransferase (ALT), inflammatory cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). Histological analysis revealed lymphocytic infiltration and silicotic nodular like lesions in liver. Collagen fibers were observed around the silicotic nodular like lesion, and hydroxyproline level in liver was also increased dramatically. We also found that activated kupffer cells (KCs) played a key role in the liver damage caused by SNs similar to alveolar macrophage in the process of silicosis. These suggest that the mechanism of liver damage caused by SNs is in consonance with the occurrence of silicosis. These findings may provide useful information for the further toxicity and bioapplication research of nanoparticles. (C) 2011 Elsevier Ltd. All rights reserved.