Solvay/GBU Silica, 69003 Lyon, France.
Chemistry and Biology of Metals, University Grenoble Alpes, CNRS UMR5249, CEA, IRIG-LCBM, 38054 Grenoble, France.
Int J Mol Sci. 2022 Dec 22;24(1):220. doi: 10.3390/ijms24010220.
Silica (either crystalline or amorphous) is widely used for different applications and its toxicological assessment depends on its characteristics and intended use. As sustained inflammation induced by crystalline silica is at the root of silicosis, investigating the inflammatory effects induced by amorphous silicas and their persistence is needed. For the development of new grades of synthetic amorphous silicas, it is also desirable to be able to understand better the factors underlying potential adverse effects. Therefore, we used an optimized in vitro macrophage system to investigate the effects of amorphous silicas, and their persistence. By using different amorphous silicas, we demonstrated that the main driver for the adverse effects is a low size of the overall particle/agglomerate; the second driver being a low size of the primary particle. We also demonstrated that the effects were transient. By using silicon dosage in cells, we showed that the transient effects are coupled with a decrease of intracellular silicon levels over time after exposure. To further investigate this phenomenon, a mild enzymatic cell lysis allowed us to show that amorphous silicas are degraded in macrophages over time, explaining the decrease in silicon content and thus the transiency of the effects of amorphous silicas on macrophages.
硅（无论是结晶态还是无定形态）被广泛应用于不同的领域，其毒理学评估取决于其特性和预期用途。由于结晶二氧化硅引起的持续炎症是矽肺的根源，因此需要研究无定形二氧化硅引起的炎症反应及其持久性。对于新型合成无定形硅的开发，也需要更好地了解潜在不良反应的潜在因素。因此，我们使用优化的体外巨噬细胞系统来研究无定形硅及其持久性的影响。通过使用不同的无定形硅，我们证明了引起不良反应的主要驱动因素是整体颗粒/团聚体的小尺寸；其次是初级颗粒的小尺寸。我们还证明了这些影响是短暂的。通过在细胞中使用硅剂量，我们表明短暂的影响与暴露后细胞内硅水平随时间的下降有关。为了进一步研究这一现象，温和的酶细胞裂解使我们能够证明无定形硅在巨噬细胞中随时间降解，这解释了硅含量的下降，从而解释了无定形硅对巨噬细胞的影响是短暂的。
