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SiO₂ nanoparticle-induced impairment of mitochondrial energy metabolism in hepatocytes directly and through a Kupffer cell-mediated pathway in vitro.

Xue Y, Chen Q, Ding T, Sun J - Int J Nanomedicine (2014)

Bottom Line: First, a buffalo rat liver (BRL) cell line was directly exposed to SiO2 nanoparticles, which induced cytotoxicity and mitochondrial damage accompanied by decreases in mitochondrial dehydrogenase activity, mitochondrial membrane potential, enzymatic expression in the Krebs cycle, and activity of the mitochondrial respiratory chain complexes I, III and IV.The supernatants from Kupffer cells treated with SiO2 nanoparticles were transferred to stimulate BRL cells.We observed that SiO2 nanoparticles had the ability to activate Kupffer cells, leading to release of tumor necrosis factor-α, nitric oxide, and reactive oxygen species from these cells and subsequently to inhibition of mitochondrial respiratory chain complex I activity in BRL cells.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Biomaterials Research and Testing Center, Shanghai Key Laboratory of Stomatology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

ABSTRACT
The liver has been shown to be a primary target organ for SiO2 nanoparticles in vivo, and may be highly susceptible to damage by these nanoparticles. However, until now, research focusing on the potential toxic effects of SiO2 nanoparticles on mitochondria-associated energy metabolism in hepatocytes has been lacking. In this work, SiO2 nanoparticles 20 nm in diameter were evaluated for their ability to induce dysfunction of mitochondrial energy metabolism. First, a buffalo rat liver (BRL) cell line was directly exposed to SiO2 nanoparticles, which induced cytotoxicity and mitochondrial damage accompanied by decreases in mitochondrial dehydrogenase activity, mitochondrial membrane potential, enzymatic expression in the Krebs cycle, and activity of the mitochondrial respiratory chain complexes I, III and IV. Second, the role of rat-derived Kupffer cells was evaluated. The supernatants from Kupffer cells treated with SiO2 nanoparticles were transferred to stimulate BRL cells. We observed that SiO2 nanoparticles had the ability to activate Kupffer cells, leading to release of tumor necrosis factor-α, nitric oxide, and reactive oxygen species from these cells and subsequently to inhibition of mitochondrial respiratory chain complex I activity in BRL cells.

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Characterization of SiO2 particles.Notes: (A) TEM analysis of SiO2 nanoparticles, (B) SEM analysis of micrometer SiO2 particles, and (C) particle size, hydrodynamic diameter, and zeta potential.Abbreviations: SEM, scanning electron microscopy; TEM, transmission electron microscopy; DMEM, Dulbecco’s Modified Eagle’s Medium; FBS, fetal bovine serum; μm-SiO2, micrometer SiO2 particles; NP, nanoparticle.
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f1-ijn-9-2891: Characterization of SiO2 particles.Notes: (A) TEM analysis of SiO2 nanoparticles, (B) SEM analysis of micrometer SiO2 particles, and (C) particle size, hydrodynamic diameter, and zeta potential.Abbreviations: SEM, scanning electron microscopy; TEM, transmission electron microscopy; DMEM, Dulbecco’s Modified Eagle’s Medium; FBS, fetal bovine serum; μm-SiO2, micrometer SiO2 particles; NP, nanoparticle.

Mentions: The primary sizes of the SiO2 particles were estimated from the TEM (Figure 1A) and SEM (Figure 1B) images, and are presented in Figure 1C. The TEM image characteristics show that the SiO2 nanoparticles were granular with a diameter of 20 nm; the SEM image characteristics show that the micrometer SiO2 particles were irregularly shaped with diameters of 0.5–6 μm. Because nanoparticles often form agglomerates in solution, the sizes of the particles and their agglomerates in suspended Dulbecco’s Modified Eagle’s Medium with 10% fetal bovine serum were estimated using dynamic light scattering. The dynamic light scattering-measured value for the SiO2 nanoparticle was larger than the particle size measured by TEM, whereas the value for the micrometer SiO2 particles was not larger than that measured by SEM (Figure 1C), indicating that the SiO2 nanoparticles formed agglomerates in the culture medium. The zeta potentials were −8.5 mV and −28.1 mV for SiO2 nanoparticles and micrometer SiO2 particles, respectively (Figure 1C).


SiO₂ nanoparticle-induced impairment of mitochondrial energy metabolism in hepatocytes directly and through a Kupffer cell-mediated pathway in vitro.

Xue Y, Chen Q, Ding T, Sun J - Int J Nanomedicine (2014)

Characterization of SiO2 particles.Notes: (A) TEM analysis of SiO2 nanoparticles, (B) SEM analysis of micrometer SiO2 particles, and (C) particle size, hydrodynamic diameter, and zeta potential.Abbreviations: SEM, scanning electron microscopy; TEM, transmission electron microscopy; DMEM, Dulbecco’s Modified Eagle’s Medium; FBS, fetal bovine serum; μm-SiO2, micrometer SiO2 particles; NP, nanoparticle.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061170&req=5

f1-ijn-9-2891: Characterization of SiO2 particles.Notes: (A) TEM analysis of SiO2 nanoparticles, (B) SEM analysis of micrometer SiO2 particles, and (C) particle size, hydrodynamic diameter, and zeta potential.Abbreviations: SEM, scanning electron microscopy; TEM, transmission electron microscopy; DMEM, Dulbecco’s Modified Eagle’s Medium; FBS, fetal bovine serum; μm-SiO2, micrometer SiO2 particles; NP, nanoparticle.
Mentions: The primary sizes of the SiO2 particles were estimated from the TEM (Figure 1A) and SEM (Figure 1B) images, and are presented in Figure 1C. The TEM image characteristics show that the SiO2 nanoparticles were granular with a diameter of 20 nm; the SEM image characteristics show that the micrometer SiO2 particles were irregularly shaped with diameters of 0.5–6 μm. Because nanoparticles often form agglomerates in solution, the sizes of the particles and their agglomerates in suspended Dulbecco’s Modified Eagle’s Medium with 10% fetal bovine serum were estimated using dynamic light scattering. The dynamic light scattering-measured value for the SiO2 nanoparticle was larger than the particle size measured by TEM, whereas the value for the micrometer SiO2 particles was not larger than that measured by SEM (Figure 1C), indicating that the SiO2 nanoparticles formed agglomerates in the culture medium. The zeta potentials were −8.5 mV and −28.1 mV for SiO2 nanoparticles and micrometer SiO2 particles, respectively (Figure 1C).

Bottom Line: First, a buffalo rat liver (BRL) cell line was directly exposed to SiO2 nanoparticles, which induced cytotoxicity and mitochondrial damage accompanied by decreases in mitochondrial dehydrogenase activity, mitochondrial membrane potential, enzymatic expression in the Krebs cycle, and activity of the mitochondrial respiratory chain complexes I, III and IV.The supernatants from Kupffer cells treated with SiO2 nanoparticles were transferred to stimulate BRL cells.We observed that SiO2 nanoparticles had the ability to activate Kupffer cells, leading to release of tumor necrosis factor-α, nitric oxide, and reactive oxygen species from these cells and subsequently to inhibition of mitochondrial respiratory chain complex I activity in BRL cells.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Biomaterials Research and Testing Center, Shanghai Key Laboratory of Stomatology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

ABSTRACT
The liver has been shown to be a primary target organ for SiO2 nanoparticles in vivo, and may be highly susceptible to damage by these nanoparticles. However, until now, research focusing on the potential toxic effects of SiO2 nanoparticles on mitochondria-associated energy metabolism in hepatocytes has been lacking. In this work, SiO2 nanoparticles 20 nm in diameter were evaluated for their ability to induce dysfunction of mitochondrial energy metabolism. First, a buffalo rat liver (BRL) cell line was directly exposed to SiO2 nanoparticles, which induced cytotoxicity and mitochondrial damage accompanied by decreases in mitochondrial dehydrogenase activity, mitochondrial membrane potential, enzymatic expression in the Krebs cycle, and activity of the mitochondrial respiratory chain complexes I, III and IV. Second, the role of rat-derived Kupffer cells was evaluated. The supernatants from Kupffer cells treated with SiO2 nanoparticles were transferred to stimulate BRL cells. We observed that SiO2 nanoparticles had the ability to activate Kupffer cells, leading to release of tumor necrosis factor-α, nitric oxide, and reactive oxygen species from these cells and subsequently to inhibition of mitochondrial respiratory chain complex I activity in BRL cells.

Show MeSH
Related in: MedlinePlus