Background Silicon dioxide nanoparticles (SiO2 NPs) are one of the most widely utilized NPs in various food sectors. However, the potential endocrine toxicity of SiO2 NPs has not been characterized. Results In the present study, mice were orally administered a series of doses of SiO2 NPs. All doses of SiO2 NPs were absorbed into the blood, liver, and pancreas of the mice. Administration of 100 mg/kg bw (body weight) of SiO2 NPs significantly increased blood glucose levels in mice. However, the same dose of SiO2 fine-particles (FPs) did not result in altered blood glucose. Whole-genome analysis showed that SiO2 NPs affected the expression of genes associated with reactive oxygen species (ROS) production and endoplasmic reticulum (ER) stress. In addition, we showed that SiO2 NPs activated xenobiotic metabolism, resulting in ER stress. Endoplasmic reticulum stress resulted in increased ROS production, which activated the NF-κB pathway leading to expression of inflammatory cytokines. Increased inflammatory cytokine expression resulted in serine phosphorylation of IRS1, which induced insulin resistance (IR). Furthermore these inflammatory cytokines activated the MAPK pathway, which further promoted the serine phosphorylation of IRS1. Insulin resistance resulted in elevated blood glucose. The ER stress inhibitor 4-phenylbutyric acid (4-PBA) inhibited SiO2 NP-induced ROS production. The ROS scavenger N-acetylcysteine (NAC) did not affect SiO2 NP-induced ER stress, but inhibited SiO2 NP-induced activation of the NF-κB and MAPK pathways, expression of inflammatory cytokines, SiO2 NP-induced serine phosphorylation of IRS1, and SiO2 NP-induced elevations of blood glucose. Conclusion Silicon dioxide NPs induced IR through ER stress and generation of ROS, but SiO2 FPs did not. Therefore, lifelong exposure of humans to SiO2 NPs may result in detrimental effects on blood glucose. The results of this study strongly suggested that non-nanoformed SiO2 should be used as food additives.

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Titanium dioxide nanoparticles (TiO2 NPs) are reported to increase plasma glucose levels in mice at specific doses. The production and accumulation of reactive oxygen species (ROS) is potentially the most important factor underlying the biological toxicity of TiO2 NPs but the underlying mechanisms are unclear at present. Data from genome‐wide analyses showed that TiO2 NPs induce endoplasmic reticulum (ER) stress and ROS generation, leading to the inference that TiO2 NP‐induced ER stress contributes to enhancement of ROS in mice. Resveratrol (Res) effectively relieved TiO2 NP‐induced ER stress and ROS generation by ameliorating expression of a common set of activated genes for both processes, signifying that ER stress and ROS are closely related. TiO2 NP‐induced ER stress occurred earlier than ROS generation. Upon treatment with 4‐phenylbutyric acid to relieve ER stress, plasma glucose levels tended toward normal and TiO2 NP increased ROS production was inhibited. These results suggest that TiO2 NP‐induced ER stress promotes the generation of ROS, in turn, triggering increased plasma glucose levels in mice. In addition, Res that displays the ability to reduce ER stress presents a dietary polyphenol antioxidant that can effectively prevent the toxicological effects of TiO2 NPs on plasma glucose metabolism.

Titanium dioxide nanoparticles (TiO2 NPs) are authorized food additives, and children have the highest exposure. Therefore, children are likely more susceptible to the adverse effects of TiO2 NPs than adults. Previous study showed that oral administration of 50 mg/kg body weight (bw) TiO2 NPs increase plasma glucose in mice. However, few studies have directly compared the adverse effects of exposure to TiO2 NPs on plasma glucose metabolism of different age groups. In this study, the developing (age 3 weeks) and adult mice (age 10 weeks) were orally administered with 50 mg/kg bw TiO2 NPs per day. The TiO2 NPs induced hyperglycemia earlier in the developing mice than in the adult mice. Then mechanisms were analyzed after mice were oral administration of TiO2 NPs for 8 weeks and 26 weeks, respectively. Results showed that the treatment with TiO2 NPs activated xenobiotic biodegradation in livers of both developing and adult mice at the early stage. However, only in the developing mice, TiO2 NPs induced endoplasmic reticulum (ER) stress in livers and increased reactive oxygen species in livers and sera in the early stage. The ER stress and ROS activated an inflammation response and mitogen‐activated protein kinase pathways, thereby inducing insulin resistance in the livers of developing mice at the early stage. The response of the adult mice was delayed, and these changes were observed in the late stage of the study. The results of this study all suggest that children are more susceptible than adults to the toxicity of orally administered TiO2 NPs.

Foodborne carbon dots (CDs), an emerging food nanocontaminant, are an increasing risk factor for metabolic toxicity in mammals. Here, we report that chronic CD exposure induced glucose metabolism disorders via disruption of the gut−liver axis in mice. 16s rRNA analysis demonstrated that CD exposure decreased the abundance of beneficial bacteria (Bacteroides, Coprococcus, and S24-7) and increased the abundance of harmful bacteria (Proteobacteria, Oscillospira, Desulfovibrionaceae, and Ruminococcaceae), as well as increased the Firmicutes/Bacteroidetes ratio. Mechanistically, the increased pro-inflammatory bacteria release the endotoxin lipopolysaccharide, which induces an intestinal inflammation and disruption of the intestinal mucus layer, activating systemic inflammation and inducing hepatic insulin resistance in mice via the TLR4/NFκB/MAPK signaling pathway. Furthermore, these changes were almost completely reversed by probiotics. Fecal microbiota transplantation from CD-exposed mice induced glucose intolerance, damaged liver function, intestinal mucus layer injury, hepatic inflammation, and insulin resistance in the recipient mice. However, microbiota-depleted mice exposed to CDs had normal levels of these biomarkers consistent with microbiota-depleted control mice, which revealed that gut microbiota dysbiosis contributes to CDinduced inflammation-mediated insulin resistance. Together, our findings revealed that gut microbiota dysbiosis contributes to CD-induced inflammation-mediated insulin resistance and attempted to elucidate the specific underlying mechanism. Furthermore, we emphasized the importance of assessing the hazards associated with foodborne CDs.