Silica nanoparticles induce liver fibrosis via TGF-β₁/Smad3 pathway in ICR mice

Abstract

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.

Effects of different sizes silica nanoparticle on the liver, kidney and brain in rats: Biochemical and histopathological evaluation

“…Chatteria et al investigated the mechanisms involved in amorphous silica nanoparticles mediated hepatotoxicity and suggested that the depletion of glutathione metabolism and increase of oxidative stress are among the principal causes of a silicamediated hepatotoxicity [38]. Yu et al [39] reported that intravenous injection of SiO2 NPs induced hepatic granuloma formation, oxidative damage, and apoptosis. Sadek et al [40] found that administration of SiNPs, for 15 consecutive days, caused changes in oxidative stress parameters such as malondialdehyde, glutathione reduced, catalase, superoxide dismutase, glutathione reductase, and glutathione peroxidase.…”

Silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro

“…Mice in control groups were injected with the same volume of saline intravenously. 12 There were ten male mice in each group. Mortality and clinical manifestations of the mice were recorded.…”

“…9,10 Our research has demonstrated that acute exposure to SiNPs can induce liver injury via macrophage infiltration and granuloma formation, 11 whereas repeated exposure to SiNPs led to liver fibrosis in vivo. 12 However, biological effects and molecular mechanisms of SiNPs on liver are still largely unknown, especially with regard to the signal-network interaction between liver and blood.…”

Targeting of Hepatic Macrophages by Therapeutic Nanoparticles

“…They produce oxidative stress that in turn modulates the autophagic process in the liver, disrupting liver metabolism and homeostasis (65). This hepatic oxidative damage has been reported in both in vitro and in vivo models for AuNPs, SiO 2 NPs, and AgNPs, with differences among the NP compositions (130)(131)(132)(133)(134). However, long-term effects need to be further characterized (65).…”