Search

It was recently shown that exposure to ZnO nanoparticles (NPs) could induce endoplasmic reticulum (ER) stress both in vivo and in vitro, but the role of ER stress in ZnO NP induced toxicity remains unclear. Because macrophages are sensitive to ER stress, we hypothesized that stressing macrophages with ER stress inducer could enhance the toxicity of ZnO NPs. In this study, the effects of ER stress inducer thapsigargin (TG) on the toxicity of ZnO NPs to THP-1 macrophages were investigated. The results showed that TG enhanced ZnO NP induced cytotoxicity as revealed by water soluble tetrazolium-1 (WST-1) and neutral red uptake assays, but not lactate dehydrogenase (LDH) assay. ZnO NPs dose-dependently enhanced the accumulation of intracellular Zn ions without the induction of reactive oxygen species (ROS), and the presence of TG did not significantly affect these effects. In the co-culture, exposure of THP-1 macrophages in the upper chamber to ZnO NPs and TG significantly reduced the viability of human umbilical vein endothelial cells (HUVECs) in the lower chamber, but the release of tumor necrosis factor α (TNFα) was not induced. In summary, our data showed that stressing THP-1 macrophages with TG enhanced the cytotoxicity of ZnO NPs to macrophages and macrophage-endothelial co-cultures., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We have recently proposed that the interaction between food components and nanoparticles (NPs) should be considered when evaluating the toxicity of NPs. In the present study, we used THP-1 differentiated macrophages as a model for immune cells and investigated the combined toxicity of low levels of palmitate (PA; 10 or 50μM) and ZnO NPs. The results showed that PA especially at 50μM changed the size, Zeta potential and UV-vis spectra of ZnO NPs, indicating a possible coating effect. Up to 32μg/mL ZnO NPs did not significantly affect mitochondrial activity, intracellular reactive oxygen species (ROS) or release of interleukin 6 (IL-6), but significantly impaired lysosomal function as assessed by neutral red uptake assay and acridine orange staining. The presence of 50μM PA, but not 10μM PA, further promoted the toxic effects of ZnO NPs to lysosomes but did not significantly affect other endpoints. In addition, ZnO NPs dose-dependently increased intracellular Zn ions in THP-1 macrophages, which was not significantly affected by PA. Taken together, the results of the present study showed a combined toxicity of low levels of PA and ZnO NPs especially to lysosomes in THP-1 macrophages., (Copyright © 2016 Elsevier B.V. All rights reserved.)