Effect of titanium dioxide nanoparticles on glucose homeostasis after oral administration.

As food additives, titanium dioxide nanoparticles (TiO2 NPs) have been widely used in various products that are usually simultaneously consumed with a high content of sugar, thus necessitating research on the effect of TiO2 NPs on glucose homeostasis. We conducted an animal study to explore the effect of orally administrated TiO2 NPs on glucose absorption and metabolism in rats at 0, 2, 10 and 50 mg kg-1 body weight day-1 for 30 and 90 days. The results showed that oral exposure to TiO2 NPs caused a slight and temporary hypoglycemic effect in rats at 30 days post-exposure but recovered at 90 days post-exposure. Decreased levels of intestinal glucose absorption and increased levels of hepatic glucose metabolism may be responsible for the hypoglycemic effect. Remodeling of the villi in the small intestine that decreased the surface area available for glucose absorption and increased levels of hepatic glucose uptake, utilization and storage related to hepatocellular injury are supposed to be the mechanisms. Our results demonstrated that dietary intake of TiO2 NPs as food additives could affect the absorption and metabolism of glucose.

Ozonized carbon black induces mitochondrial dysfunction and DNA damage.

Black carbon and tropospheric ozone (O3 ), which are major air pollutants in China, are hazardous to humans following inhalation. Black carbon can be oxidized by O3 forming secondary particles of which the health effects are unknown. The present study utilized carbon black as a representative of black carbon to characterize the cytotoxicity induced by secondary particles in bronchial epithelial cells (16HBE) and C57BL/6J mice, and to investigate the implicated molecular pathways. Two types of carbon black including untreated carbon black (UCB) and ozonized carbon black (OCB) were presented. The effects of carbon black on cell viability, intracellular reactive oxygen species (ROS), oxidized/reduced glutathione ratio, mitochondrial membrane potential (MMP), intracellular ATP, and mitochondrial cytochrome c to cytoplasmic cytochrome c ratio were assessed in 16HBE. In addition, an alkaline comet assay and a cytokinesis-block micronucleus (CBMN) test with 16HBE cells in vitro and ELISA method for serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) and a bone marrow micronucleus (BMN) test with C57BL/6J mice in vivo were performed to detect the genotoxicity. When compared with UCB exposed cells, OCB exposed cells had decreased cell viability, increased cell death rate, increased comet length and decreased MMP at 24 h exposure. UCB induced higher level of intracellular ROS than OCB from 4 to 23 h. No changes were observed for both OCB and UCB in serum 8-OHdG, intracellular ATP and mitochondrial cytochrome c to cytoplasmic cytochrome c ratio. The results of CBMN and BMN tests are negative. Intracellular ROS induced by OCB was lower than that of UCB. In summary, ozonization enhances the mitochondrial toxicity and genotoxicity of carbon black. Oxidative stress may not dominate in toxic effects of OCB. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 944-955, 2017.

[Effect of 1,4-naphthoquinone aged black carbon on reactive oxygen species and DNA strand breaks in human bronchial epithelial cells].

OBJECTIVE: To study the effect of 1,4-naphthoquinone aged black carbon (BC/1,4-NQ) on reactive oxygen species and DNA strand breaks in human bronchial epithelial cells (16HBE). METHODS: In the study, 16HBE cells were exposed to BC/1,4-NQ, BC and 1,4-NQ at the concentrations of BC/1,4-NQ (10.0/0.2, 20.0/0.4, 40.0/0.8, 80.0/1.6, 160.0/3.2 mg/L), BC (10.0, 20.0, 40.0, 80.0, 160.0 mg/L), 1,4-NQ (0.2, 0.4, 0.8, 1.6, 3.2 mg/L) for 24, 48, and 72 h, respectively. Cytotoxicity was detected by cell count kit 8 (CCK-8) at the end point. Then the 16HBE cells were exposed to BC/1,4-NQ (20.0/0.4, 40.0/0.8, 80.0/1.6 mg/L), BC (20.0, 40.0, 80.0 mg/L), 1,4-NQ (0.4, 0.8, 1.6 mg/L) for 24 h. The reactive oxygen species (ROS) generation was determined via flow cytometry with DCFH-DA probe. Single cell gel electrophoresis (SCGE) assay was performed to evaluate genotoxicity by Olive tail moment (OTM) value. RESULTS: Except for the concentration of 10.0/0.2 mg/L within the exposure time 24 h, the cell viabilities of BC/1,4-NQ were significantly lower than the control (P<0.05) within the exposure time 24-72 h, showing a dose-dependent cytotoxicity. Especially, BC/1,4-NQ showed greater cytotoxicity than BC single exposure, lower than 1,4-NQ at the concentration of BC/1,4-NQ≥80.0/1.6 mg/L. BC/1,4-NQ also showed greater ROS generation and OTM value than the control within the exposure time 24 h at each concentration (P<0.05). Especially, the ROS generation and OTM value of BC/1,4-NQ were greater than BC single exposure, lower than 1,4-NQ at the concentration of 80.0/1.6 mg/L (P<0.05). CONCLUSION: BC/1,4-NQ can induce intracellular ROS generation, cytotoxicity and genotoxicity in 16HBE cells. And at high concentration, the intracellular ROS level, cytotoxicity and genotoxicity induced by BC/1,4-NQ were greater than those by BC single exposure, but lower than those by 1,4-NQ.

[Comparison of genetic damage in mice exposed to black carbon and ozone-oxidized black carbon].

OBJECTIVE: To make an assessment on the genotoxicity caused by black carbon (BC) and ozonized black carbon (O3-BC). METHODS: In this study, 74 healthy male ICR mice [weighed (28 ± 1.5) g] were randomly divided into 7 groups, including one phosphate buffer solution (PBS) control group and six particles exposed groups by intratracheal instillation with either BC or O3-BC at the doses of 50, 100, 200 µg/mouse, respectively. There were 12 mice in the groups of 200 µg/mouse and 10 mice in others. The mice were sacrificed 24 h after four intratrachealinstillations. The activities of catalase (CAT) in serum and the levels of malondialdehyde (MDA) in lung tissue homogenate were measured. As the DNA damage mark, 8-hydroxyguanosine (8-OHdG) in urine and serum were quantified with ELISA method. Micronucleus test was used for potential genotoxicity of BC and O3-BC. Hematoxylin and eosin staining was used to stain lung paraffin section. RESULTS: The mice were in good condition during instillation, and the liver coefficient of the test groups was significantly lower than that of the control group (P<0.05). The activities of CAT in serum significantly increased in the 100 µg/mouse and 200 µg/mouse groups after being exposed to these two kinds of particles. The micronucleus rate in allthe BC and O3-BC exposed groups increased (P<0.05), but there was no statistically significant difference among the groups in the levels of 8-OHdG in serum and urine and MDA in lung tissue homogenate. Inflammatory response was found in the lung tissue under the microscope after exposure to BC and O3-BC. CONCLUSION: Intratracheal instillation of BC and O3-BC induced increasing of oxidative stress and genetic damage in mice. But there was no significant difference between these two particles in toxicity. Whether the genotoxicity of O3-BC is higher than that of BC or not is uncertain. Further research is needed.

Effect of titanium dioxide nanoparticles on the cardiovascular system after oral administration.

Titanium dioxide nanoparticles (TiO2 NPs) have been widely used in various consumer products, especially food and personal care products. Compared to the well-characterized adverse cardiovascular effect of inhaled ambient ultrafine particles, research on the health response to orally administrated TiO2 NPs is still limited. In our study, we performed an in vivo study in Sprague-Dawley rats to understand the cardiovascular effect of TiO2 NPs after oral intake. After daily gastrointestinal administration of TiO2 NPs at 0, 2, 10, 50 mg/kg for 30 and 90 days, heart rate (HR), blood pressure, blood biochemical parameters and histopathology of cardiac tissues was assessed to quantify cardiovascular damage. Mild and temporary reduction of HR and systolic blood pressure as well as an increase of diastolic blood pressure was observed after daily oral administration of TiO2 NPs for 30 days. Injury of cardiac function was observed after daily oral administration of TiO2 NPs for 90 days as reflected in decreased activities of lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH) and creatine kinase (CK). Increased white blood cells count (WBC) and granulocytes (GRN) in blood as well as increased concentrations of tumor necrosis factor α (TNF α) and interleukin 6 (IL-6) in the serum indicated inflammatory response initiated by TiO2 NPs exposure. It was hypothesize that cardiac damage and inflammatory response are the possible mechanisms of the adverse cardiovascular effects induced by orally administrated TiO2 NPs. Data from our study suggested that even at low dose of TiO2 NPs can induce adverse cardiovascular effects after 30 days or 90 days of oral exposure, thus warranting concern for the dietary intake of TiO2 NPs for consumers.