Toxic effects of zinc oxide nanoparticles combined with vitamin C and casein phosphopeptides on gastric epithelium cells and the intestinal absorption of mice

Zinc oxide nanomaterials have become common food additives in recent years. Casein phosphopeptides (CPP) and vitamin C (VC) are used as functional food additives together with ZnO nanoparticles (ZnO NPs) in many commercial foods. Our previous studies showed that VC can increase the cytotoxicity induced by ZnO NPs both in vitro and in vivo, while CPP can have a cytoprotective effect against oxidative stress induced by ZnO NPs. However, the combined toxic effect of the three additives together in food is unknown. Herein, we have investigated the combined toxicity of ZnO NPs, CPP and VC by altering the sequence of their addition to clarify their toxic mechanisms in the composite systems. When the order of addition of the three materials changes, the cytotoxicity induced by the ZnO NPs changes due to the different concentrations of dissolved Zn ions in the different groups. We have also probed the intestinal absorption of Zn ions with an everted gut sac model. The amount of Zn2+ absorbed in the intestine in different composite systems also responds differently to the sequence of addition of the additives. VC is more powerful at controlling the synergistic toxic effect induced by ZnO NPs compared to the protective role of CPP in the combined systems.