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

Yang Xue, Qingqing Chen, Tingting Ding, Jiao Sun

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.

Keywords: SiO₂ nanoparticles, mitochondria-associated energy metabolism, buffalo rat liver cells, Kupffer cells

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