Silica nanoparticles induce liver fibrosis via TGF-β(1)/Smad3 pathway in ICR mice

The liver is one of the target organs of silica nanoparticles (SiO(2) NPs) but the toxic mechanism on the liver still remains unclear. This study aimed to explore the hepatic toxicity and its mechanism through repeated intravenous exposure to SiO(2) NPs in ICR mice. Results indicated that SiO(2) NPs could be distributed in hepatocytes, Kupffer cells, and hepatic stellate cells, and induce hepatic dysfunction as well as granuloma formation in the liver. The increase of lipid peroxide level and decrease of antioxidant enzyme activities in the liver indicated that SiO(2) NPs could induce hepatic oxidative damage. SiO(2) NPs induced hepatocytes’ apoptosis shown by morphological examination and TUNEL assay. The results of Masson’s trichrome staining and hydroxyproline assay showed hyperplasia of collagen fibers in the liver, suggesting SiO(2) NPs caused liver fibrosis, and it was promoted by oxidative damage and hepatocytes’ apoptosis. The results of Western blot analysis and immunohistochemical staining indicated that the activation of TGF-β(1)/Smad3 signaling pathway played an important role in this pathophysiological process. The results suggested that oxidative damage and hepatocyte apoptosis activated TGF-β(1)/Smad3 signaling pathway, and thus promoted the process of liver fibrosis induced by intravenous injection of SiO(2) NPs in mice. This study, for the first time, investigated liver fibrosis and its related mechanism induced by repeated intravenous exposure of amorphous SiO(2) NPs, and provides important experimental evidence for safety evaluation of SiO(2) NPs, especially in biomedical application.