Palmitate enhanced the cytotoxicity of ZnO nanomaterials possibly by promoting endoplasmic reticulum stress

Abstract

We recently synthesized ZnO nanomaterials (denoted as ZnO nanorods [NRs] and Mini‐NRs) and suggested that their cytotoxicity could be related with the activation of endoplasmic reticulum (ER) stress apoptosis. However, in a complex biological microenvironment, the ER stress‐apoptosis pathway could also be modulated by biological molecules, such as free fatty acids, leading to unpredicted biological effects. In this study, we investigated the combined toxicity of ZnO NRs/Mini‐NRs and palmitate (PA) to THP‐1 macrophages. PA influenced the zeta potential and solubility of ZnO NRs and ZnO Mini‐NRs in water, which indicated a change of colloidal stability. Exposure to ZnO NRs and Mini‐NRs dose‐dependent decreased cellular viability and release of soluble monocyte chemotactic protein 1 (sMCP‐1), and these effects were significantly promoted with the presence of PA. However, ZnO NR‐ and Mini‐NR‐induced intracellular Zn ions or reactive oxygen species were not significantly affected by PA. ZnO NRs and ZnO Mini‐NRs significantly promoted the expression of ER stress genes HSPA5, DDIT3, XBP‐1s and apoptotic gene CASP3, whereas PA also modestly promoted the expression of HSPA5, DDIT3 and CASP3. Interestingly, the ER stress inducer thapsigargin showed a similar effect as PA to promote the cytotoxicity of ZnO NRs and ZnO Mini‐NRs. It is suggested that PA might promote the cytotoxicity of ZnO NRs and ZnO Mini‐NRs possibly by promoting ER stress.

Comparison of toxicity of Ti3C2 and Nb2C Mxene quantum dots (QDs) to human umbilical vein endothelial cells

“…However, the results from this study showed that Mxene QDs induced cytotoxicity but reduced the release of inflammatory mediators (Figure 6). A recent study obtained similar data that ZnO nanorods significantly induced cytotoxicity but reduced inflammatory mediator releases in THP‐1 macrophages (Chen et al, 2019). Thus, it is unlikely that Mxene QDs led to cytotoxicity by the induction of inflammatory responses.…”

Potential roles of Kruppel‐like factors in mediating adverse vascular effects of nanomaterials: A review

“…Guo et al also showed that co‐exposure to SiO 2 NPs and oxidized low‐density lipoprotein (oxLDL) transformed macrophages into foam cells through ER stress‐mediated up‐regulation of scavenger receptors as well as inhibition of cholesterol efflux genes (Guo, Ma, et al, 2018). However, it should be noticed that the presence of lipids could influence NM‐induced macrophage foam cell formation, therefore it will be necessary to investigate the effects of NMs without additional supply of lipids (J. Chen et al, 2019; Q. Yang et al, 2019). Our group showed that MWCNTs promoted lipid accumulation in THP‐1 macrophages without the presence of lipids.…”

The cytotoxicity of zinc oxide nanoparticles to 3D brain organoids results from excessive intracellular zinc ions and defective autophagy

“…5B-D). We previously found that the same type of ZnO NPs also induced excessive intracellular Zn ions but not oxidative stress (Luo et al 2018;Chen et al 2019;Cao et al 2022). Others have shown that stabilizing ZnO NPs with oleate reduced the intracellular concentrations of Zn ions and consequently alleviated NP-induced cytotoxicity to HepG2 and Caco-2 cells (Fang et al 2017).…”