Toxicity of combined exposure of ZnO nanoparticles (NPs) and myricetin to Caco-2 cells: changes of NP colloidal aspects, NP internalization and the apoptosis-endoplasmic reticulum stress pathway

Abstract

Phytochemicals as typical food components may significantly influence the toxicity of nanoparticles (NPs) in intestinal cells, indicating a need to evaluate the toxicological effects of NPs in a complex situation. Previous studies suggested that the anti-oxidative properties of phytochemicals were important to elicit cytoprotective effects against NP exposure. However, we recently found that the changes of signaling pathways may be more important for cytoprotective effects of phytochemicals. In this study, we investigated the influence of myricetin (MY) on the cytotoxicity of ZnO NPs in Caco-2 cells and the possible mechanism. MY at 50 μM showed minimal impact on the solubility and colloidal aspects of ZnO NPs, but protected Caco-2 cells from NP exposure as it increased the EC50 value. For comparison, dihydromyricetin (DMY; chemical analog of MY) increased the EC50 value to a much lesser extent. Exposure to ZnO NPs significantly induced intracellular Zn ions, whereas MY or DMY did not significantly influence the internalization of NPs. However, ZnO NPs significantly promoted the ratio of caspase-3/pro-caspase-3, which was inhibited by the presence of MY. Exposure to ZnO NPs did not significantly promote the biomarkers of endoplasmic reticulum (ER) stress, but co-exposure to ZnO NPs and MY significantly lowered the levels of a panel of ER stress biomarkers. In conclusion, these results suggested that MY could protect Caco-2 cells from ZnO NP exposure, which may not be related to the changes of colloidal stability or internalization of NPs but could be alternatively related to the reduction of ER stress leading to lower cleaved caspase-3.

Comparison Study of Cytotoxicity of Bare and Functionalized Zinc Oxide Nanoparticles

“…In addition, this type of cell line is commonly used in the pharmaceutical industry as an in vitro model of the human small intestine mucosa to predict the absorption of orally administered drugs [50,51]. Moreover, Caco-2 cells were used as model to assess the toxicity of ZnO NPs in many studies [52][53][54][55]. The application of mouse fibroblast L929 cells is most frequently undertaken to evaluate cytotoxicity and may represent a sufficient in vitro screening model for skin formulations [56][57][58].…”

Comparison of cytotoxicity of Ag/ZnO and Ag@ZnO nanocomplexes to human umbilical vein endothelial cells in vitro

“…Exposure to NPs may perturb the normal functions of ER leading to a condition termed as ER stress, which can ultimately lead to the toxic effects of NPs (Cao, Long, et al, 2017; N. Liu & Tang, 2020). Previous studies showed that ZnO NPs induced ER stress leading to the apoptosis of cells (T. Liu et al, 2019; Wang et al, 2019; Wu, Luo, Liu, Xie, & Cao, 2019). Hereby, we also found that ZnO NPs at cytotoxic concentration significantly induced the expression of ER stress genes (Figure 4) as well as apoptotic caspase 3 gene (Figure S5).…”

Antimicrobial Properties of Food Nanopackaging: A New Focus on Foodborne Pathogens

“…Caco-2 cells could be protected from ZnONP exposure by myricetin through modulating the apoptosis-ER stress pathway. In fact, co-exposure to myricetin and ZnONPs led to a significantly reduced ratio of cleaved caspase-3/pro-caspase-3 compared with the exposure to ZnONPs ( Wu et al, 2019 ).…”