Potential mitigation of titanium dioxide nanoparticles against 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis through inhibiting the canonical NF-κB pathway.

Titanium dioxide nanoparticles (TiO2 NPs) have been widely employed in various industry fields, which makes consumers concerned about their health impact. Our previous work displayed that TiO2 NPs participated in the mitigation of TNBS-induced colitis, but the mechanism is still unknown. This work aimed to explore the role of oxidative stress and NF-κB pathway in the effect of TiO2 NPs on TNBS-induced colitis. The results showed that TiO2 NPs administration reduced the DAI score of colitis mice after TNBS enema. TiO2 NPs did not alter oxidative stress status (GSH/GSSG), but repaired the gut dysbacteriosis and inhibited the canonical NF-κB pathway activation in TNBS-induced colitis mice, manifested as a decrease in pathogenic bacteria and an increase in beneficial bacteria, as well as down-regulation of toll-like receptors (TLRs), IKKα, IKKß, p65 and pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α and IFN-γ) in mRNA level, and the increased transcription of anti-inflammatory cytokines (IL-10, TGF-ß, and IL-12), along with the declined protein level of TNF-α in TiO2 NPs treated colitis mice. The present study suggested that oral TiO2 NPs administration inhibited the canonical NF-κB pathway activation by repairing gut dysbacteriosis, which made a predominant role in alleviating colitis. These findings provided a new perspective for exploring the safety of TiO2 NPs.

Oral intake of titanium dioxide nanoparticles affect the course and prognosis of ulcerative colitis in mice: involvement of the ROS-TXNIP-NLRP3 inflammasome pathway.

BACKGROUND: Titanium dioxide (TiO2), no matter in nanoscale or micron sizes, has been widely used in food industry as additives for decades. Given the potential impact of TiO2 on the gastrointestinal epithelial and parenchymal cells, including goblet cells, the public consumers may suffer the risk of diseases caused by its widespread dissemination in food products. We therefore set out to investigate the impact of TiO2 NPs on the course and prognosis of ulcerative colitis by oral gavaging TiO2 NPs at the doses levels of 0, 30, 100, and 300 mg/kg during the induction (7 days, from day 1 to day 7) and recovery (10 days, from day 8 to day 17) phases of colitis in mice. RESULTS: The ulcerative colitis (UC) disease model was established by administrating of 2.5% dextran sulfate sodium (DSS) solution. Our results show that TiO2 NPs significantly enhanced the severity of DSS-induced colitis, decreased the body weight, increased the disease activity index (DAI) and colonic mucosa damage index (CMDI) scores, shortened the colonic length, increased the inflammatory infiltration in the colon. The most significant changes occurred in the low dose (30 mg/kg) group of TiO2 NPs exposure during the development phase of UC and the high dose (300 mg/kg) group of TiO2 NPs during UC self-healing phase. Increased reactive oxygen species (ROS) level and upregulation of anti-oxidant enzymes including total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-PX) and catalase (CAT), demonstrate that the TiO2 NP exposure has triggered oxidative stress in mice. Moreover, the upregulation of caspase-1 mRNA and increased expression of thioredoxin interacting protein (TXNIP) further demonstrate the involvement of the ROS-TXNIP-NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway in aggravating the development of UC. CONCLUSION: Oral intake of TiO2 NPs could affect the course of acute colitis in exacerbating the development of UC, prolonging the UC course and inhibiting UC recovery.

A case study on occupational exposure assessment and characterization of particles in a printing shop in China.

Printers can release numerous particles to contaminate indoor environments and pose health risks. Clarifying the exposure level and physicochemical properties of printer-emitted particles (PEPs) will help to evaluate the health risks of printer operator. In our study, the particles concentration in the printing shop was monitored in real time for a long time (12 h/day, total 6 days), and the PEPs were collected to characterize their physicochemical properties including shape, size and compositions. The result showed that the concentration of PEPs is closely related to the printing workload and the highest particle mass concentration of PM10 and PM2.5 was 212.73 µg m-3 and 91.48 µg m-3, respectively. The concentration of PM1 in the printing shop was in the range of 11.88-80.59 µg m-3 for mass value, and 174.83-1348.84 P cm-3 for count value which changed with the printing volume. The particle sizes of PEPs were less than 900 nm, 47.99% of PEPs was less than 200 nm, and 14.21% of the particles were at the nanoscale. PEPs contained 68.92% organic carbon (OC), 5.31% elemental carbon (EC), 3.17% metal elements, and 22.60% other inorganic additives, which contained more OC and metal elements than toners. Total polycyclic aromatic hydrocarbons (PAHs) levels were 18.95 ng/mg in toner and 120.70 ng/mg in PEPs. The carcinogenic risk of PAHs in PEPs was 1.40 × 10-7. These findings suggested future studies should pay more attention to the health effects of printing workers exposed to nanoparticles.

Characterization of titanium dioxide nanoparticles in confectionary products and estimation of dietary exposure level among the Chinese population.

Titanium dioxide (TiO2) is widely used in the food industry. Recently, European Commission has banned TiO2 as a food additive, raising public concern about its health risk, especially the nanoparticles (NPs) contained therein. This study aimed to reveal the existence of TiO2 NPs in food and further estimate the dietary exposure level among Chinese population by characterizing particle size distribution, determining Ti content and micro-distribution in food products, and calculating food consumption from the China Health and Nutrition Survey (CHNS). The results showed that TiO2 particle size in food additives and chewing gums was 53.5-230.3 nm and 56.8-267.7 nm respectively, where NPs accounted for 34.7% and 55.6% respectively. TiO2 was firstly in situ presented on the surface of confectionary products with hard shells. The content of TiO2 ranged from 3.2 to 3409.3 µg/g product. Besides, the mean dietary intake was 71.31 µg/kgbw/day for TiO2 and 7.75 µg/kgbw/day for TiO2 NPs among Chinese population, affected by people's dietary habits of different regions. Children's exposure levels was the highest due to their love of sweets. More attention should be paid to risk assessment and management of TiO2 NPs for children in China.

Changes in heart rate variability of healthy subjects shortly exposed to printing shop particles and the effect of air purifier intervention.

Particulate matter (PM) released by printers may cause airway inflammation and cardiac electrophysiological changes. We conducted a two-stage crossover study to examine the association between short-term exposure to printing shop particles (PSPs) and the heart rate variability (HRV) among healthy volunteers, as well as to evaluate the effect of air purifier intervention. The on-site assessments of PSPs and individual HRV parameters of the volunteers were used to analyze the influence of size-fractionated PSPs and air purifier intervention on HRV at different lag times after PSPs exposure (0 min, 5 min, 15 min, and 30 min) by using the linear mixed-effects models. We observed that changes in 6 HRV parameters were associated with particle mass concentration (PMC) of PSPs, and changes in 8 HRV parameters were associated with particle number concentration (PNC) of PSPs. The sensitive HRV parameters were the square root of the mean of the sum of the squares of differences between adjacent NN intervals (rMSSD), NN50 count divided by the total number of all NN intervals (pNN50), normalized high frequency power (nHF), very high frequency power (VHF), normalized low frequency power (nLF), and the ratio of low frequency power to high frequency power (LF/HF). Most HRV parameters exhibited the strongest effect associated with PMC and PNC at a lag time of 30 min. The air purifier intervention markedly reduced the PNC and PMC of size-fractionated PSPs, enhanced 5 HRV parameters, and decreased the nLF and LF/HF. Our study suggests that short-term exposure to PSPs can affect HRV parameters, reflecting changes in cardiac autonomic nervous activity, and the use of an air purifier can reduce the concentration of PSPs and improve the autonomic nervous system activity of the exposed individuals.

The Influence of Long-Term Dietary Intake of Titanium Dioxide Particles on Elemental Homeostasis and Tissue Structure of Mouse Organs.

Background: Titanium dioxide (TiO2), consisting of nanoparticles and sub-microparticles, were widely used as food additive and consumed by people every day, which has aroused a public safety concern. Some studies showed TiO2 can be absorbed by intestine and then distributed to different tissues after oral intake, which is supposed to affect the content of various elements in the body whereas led to tissue damage. However, knowledge gaps still exist in the impact of TiO2 on the disorder of elemental homeostasis. Thus, this study aimed to explore the oral toxicity of TiO2 by assessing its influence on elemental homeostasis and tissues injury. Method: ICR mice were fed with normal feed, TiO2 nanoparticles (NPs)-mixed feed or TiO2 submicron particles (MPs)-mixed feed (1% mass fraction TiO2 NPs or MPs were mixed in commercial pellet diet) for 1, 3, and 6 months. Particles used in this study were characterized. The distribution of Ti and other 23 elements, the correlation among elements, and pathological change in the liver, kidney, spleen and blood cells of the mice was determined. Result: Ti accumulation only appeared in blood cells of mice treated with TiO2 MPs-mixed feed for 6 months, but TiO2 cause 12 kinds of elements (boron, vanadium, iron, cobalt, copper, zinc, selenium, sodium, calcium, magnesium, silicon, phosphorus) content changed in organ tissue. The changed kinds of elements in blood cells (6 elements), liver (7 elements) or kidney (6 elements) were more than in the spleen (1 element). The TiO2 NPs induced more elements changed in blood cells and liver, and the TiO2 MPs induced more elements changed in kidney. Significantly positive correlation between Ti and other elements was found in different organs except the liver. Organ injuries caused by TiO2 NPs were severer than TiO2 MPs. Liver exhibited obvious pathological damage which became more serious with the increase of exposure time, while kidney and spleen had slight damages. Conclusion: These results indicated long-time dietary intake of TiO2 particles could induce element imbalance and organ injury. The liver displayed more serious change than other organs, especially under the treatment with TiO2 NPs. Further research on the oral toxicity of TiO2 NPs should pay more attention to the health effects of element imbalances using realistic exposure methods.

Impact of titanium dioxide nanoparticles on intestinal community in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis mice and the intervention effect of vitamin E.

Titanium dioxide nanoparticles (TiO2-NPs) are widely applied as additives in foods due to their excellent whitening and brightening capability. Although the toxicity and antibacterial activity of TiO2-NPs have been extensively studied, their impact on the gut microbiota in vivo still remains unclear, especially in animals with gastrointestinal disorders. In the present study, healthy mice and TNBS-induced colitis mice were administered with TiO2-NPs (38.3 ± 9.3 nm) orally at a dose of 100 mg per kg bw daily for 10 days to study the impact of TiO2-NPs on the gut microbiota and colitis development. Moreover, the mechanism of TiO2-NPs on the gut microbiota was also discussed when the colitis mice were additionally administered with vitamin E to remove ROS. Changes in the microbiota community structure and gut-associated function prediction were analyzed through bioinformatics. The result showed that the oral administration of TiO2-NPs mitigated colitis symptoms by reducing the DAI and CMDI scores and TNF-α level. Furthermore, 16S rDNA sequencing analysis showed that the structure and function prediction of gut microbiota could be modified in healthy mice and colitis mice after exposure to TiO2-NPs, but the opposite physiological effect occurred since the dominant flora varied in these two groups. Moreover, vitamin E intervention did not change the effects of TiO2-NPs on the microbiota community structure and gut-associated function, which indicates that the mechanism of the biological effects of TiO2-NPs on the gut microbiota may not be associated with their ability to induce the generation of ROS. In summary, our work firstly found that TiO2-NPs could regulate the gut microbiota of colitis mice and participate in the mitigation of TNBS-induced acute colitis, and the capability of TiO2-NPs to induce the generation of ROS inducement did not contribute to this process.

Health effects of occupational exposure to printer emissions on workers in China: Cardiopulmonary function change.

Printers emitted nanoparticles (NPs), ozone (O3) and volatile organic chemicals (VOCs) during operation that elicited adverse effects on indoor air quality of the printing room, which may affect the health of exposed workers. The aim of this work was to explore the health effects of occupational exposure to printer emissions on workers, especially cardiovascular and lung function. We sampled particles in the print shop for characterization, including particle size distribution and elemental composition, and measured PM1 number concentrations in print shops and other workplaces. We assessed blood pressure, heart rate and pulmonary function in 53 printing room workers and 54 controls in Beijing, China. Multiple linear regression analysis were used to examine health effects of exposure to printer emissions. The PM1 number concentration in the print shop was more than 2 times that of the control group. Compared with controls, the exposed workers with lower education and income had heavier workload with a median of 7 days per week and 12 h per day on working days, and presented cardiopulmonary function injury with increased the diastolic blood pressure (DBP), systolic blood pressure (SBP), and mean arterial pressure (MAP). The most significant changes of cardiopulmonary function were found in exposed workers with more than 10 years of working age. Multiple linear regression also showed printer emissions exposure was associated with increased SBP and MAP, while decreased lung function indices. This study found changes in the cardiopulmonary function of staff members exposed to printer emissions, which prompted the necessity and urgency of improving the environment of printing rooms and protecting the health of exposed workers.