International Journal of Nanomedicine (Aug 2017)

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

  • Yu Y,
  • Duan J,
  • Li Y,
  • Li Y,
  • Jing L,
  • Yang M,
  • Wang J,
  • Sun Z

Journal volume & issue
Vol. Volume 12
pp. 6045 – 6057

Abstract

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Yang Yu,1,2 Junchao Duan,1,2 Yang Li,1,2 Yanbo Li,1,2 Li Jing,1,2 Man Yang,1,2 Ji Wang,1,2 Zhiwei Sun1,2 1School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, People’s Republic of China Abstract: The liver is one of the target organs of silica nanoparticles (SiO2 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 SiO2 NPs in ICR mice. Results indicated that SiO2 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 SiO2 NPs could induce hepatic oxidative damage. SiO2 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 SiO2 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-β1/Smad3 signaling pathway played an important role in this pathophysiological process. The results suggested that oxidative damage and hepatocyte apoptosis activated TGF-β1/Smad3 signaling pathway, and thus promoted the process of liver fibrosis induced by intravenous injection of SiO2 NPs in mice. This study, for the first time, investigated liver fibrosis and its related mechanism induced by repeated intravenous exposure of amorphous SiO2 NPs, and provides important experimental evidence for safety evaluation of SiO2 NPs, especially in biomedical application. Keywords: silica nanoparticles, oxidative stress, hepatocyte apoptosis, fibrosis, TGF-β1/Smad3 signaling pathway

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