Copper oxide nanoparticles (CuO NPs) are increasingly used in various industry sectors. Moreover, medical application of CuO NPs as antimicrobials also contributes to human exposure. Their toxicity, ...including toxicity to the immune system and blood, raises concerns, while information on their immunotoxicity is still very limited. The aim of our work was to evaluate the effects of CuO NPs (number concentration 1.40×10
particles/cm
, geometric mean diameter 20.4 nm) on immune/inflammatory response and antioxidant defense in mice exposed to 32.5 µg CuO/m
continuously for 6 weeks. After six weeks of CuO NP inhalation, the content of copper in lungs and liver was significantly increased, while in kidneys, spleen, brain, and blood it was similar in exposed and control mice. Inhalation of CuO NPs caused a significant increase in proliferative response of T-lymphocytes after mitogenic stimulation and basal proliferative activity of splenocytes. CuO NPs significantly induced the production of IL-12p70, Th1-cytokine IFN-γ and Th2-cytokines IL-4, IL-5. Levels of TNF-α and IL-6 remained unchanged. Immune assays showed significantly suppressed phagocytic activity of granulocytes and slightly decreased respiratory burst. No significant differences in phagocytosis of monocytes were recorded. The percentage of CD3
, CD3
CD4
, CD3
CD8
, and CD3
CD19
cell subsets in spleen, thymus, and lymph nodes did not differ between exposed and control animals. No changes in hematological parameters were found between the CuO NP exposed and control groups. The overall antioxidant protection status of the organism was expressed by evaluation of GSH and GSSG concentrations in blood samples. The experimental group exposed to CuO NPs showed a significant decrease in GSH concentration in comparison to the control group. In summary, our results indicate that sub-chronic inhalation of CuO NPs can cause undesired modulation of the immune response. Stimulation of adaptive immunity was indicated by activation of proliferation and secretion functions of lymphocytes. CuO NPs elicited pro-activation state of Th1 and Th2 lymphocytes in exposed mice. Innate immunity was affected by impaired phagocytic activity of granulocytes. Reduced glutathione was significantly decreased in mice exposed to CuO NPs.
Titanium dioxide nanoparticles (TiO
NPs) are used in a wide range of applications. Although inhalation of NPs is one of the most important toxicologically relevant routes, experimental studies on ...potential harmful effects of TiO
NPs using a whole-body inhalation chamber model are rare. In this study, the profile of lymphocyte markers, functional immunoassays, and antioxidant defense markers were analyzed to evaluate the potential adverse effects of seven-week inhalation exposure to two different concentrations of TiO
NPs (0.00167 and 0.1308 mg TiO
/m
) in mice. A dose-dependent effect of TiO
NPs on innate immunity was evident in the form of stimulated phagocytic activity of monocytes in low-dose mice and suppressed secretory function of monocytes (IL-18) in high-dose animals. The effect of TiO
NPs on adaptive immunity, manifested in the spleen by a decrease in the percentage of T-cells, a reduction in T-helper cells, and a dose-dependent decrease in lymphocyte cytokine production, may indicate immunosuppression in exposed mice. The dose-dependent increase in GSH concentration and GSH/GSSG ratio in whole blood demonstrated stimulated antioxidant defense against oxidative stress induced by TiO
NP exposure.
Purpose
To determine the DNA protective effects of a standard coffee beverage in comparison to water consumption.
Methods
The single-blind, randomised controlled study with parallel design included ...healthy women (
n
= 50) and men (
n
= 50) recruited from the general Central European population. The subjects were randomised in a coffee and a control group, with stratification for sex and body mass index. The study comprised two periods of 4 weeks: a preconditioning period, with daily consumption of at least 500 ml water but no coffee, nor tea, nor any other caffeine-containing product. During the subsequent intervention period the coffee group consumed 500 ml of freshly brewed dark roast coffee blend per day, the control group consumed water instead. On the last day of each period, blood was drawn and analysed by comet assay (single-cell gel electrophoresis) to assess the level of DNA damage (strand breakage).
Results
At the end of the intervention period the mean level of DNA strand breaks in the coffee group has decreased in comparison to the control group difference in means 0.23% TI (tail intensity),
p
= 0.028. The mean change from baseline (delta value) was − 23% in the coffee group (
p
= 0.0012). Effects of coffee intake were similar for men and women. During intervention, neither group showed any significant change in body weight or calorie intake.
Conclusions
Our results indicate that regular consumption of a dark roast coffee blend has a beneficial protective effect on human DNA integrity in both, men and women.
This study aims to investigate the in vitro effects of nanoparticles (NPs) produced during the selective laser melting (SLM) of 316 L stainless steel metal powder on the immune response in a human ...blood model. Experimental data did not reveal effect on viability of 316 L NPs for the tested doses. Functional immune assays showed a significant immunosuppressive effect of NPs. There was moderate stimulation (117%) of monocyte phagocytic activity without significant changes in phagocytic activity and respiratory burst of granulocytes. A significant dose-dependent increase in the levels of the pro-inflammatory cytokine TNF-a was found in blood cultures treated with NPs. On the contrary, IL-8 chemokine levels were significantly suppressed. The levels of the pro-inflammatory cytokine IL-6 were reduced by only a single concentration of NPs. These new findings can minimise potential health risks and indicate the need for more research in this area.
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•Laser melting of stainless steel emits nanoparticles.•Detailed observation and characterization of nanoparticle contamination.•In vitro evaluation of immunotoxicity of nanoparticles using human blood cells..
In 2012, a controversial study on the long-term toxicity of a Roundup herbicide and the glyphosate-tolerant genetically modified (GM) maize NK603 was published. The EC-funded G-TwYST research ...consortium tested the potential subchronic and chronic toxicity as well as the carcinogenicity of the glyphosate-resistant genetically modified maize NK603 by performing two 90-day feeding trials, one with GM maize inclusion rates of 11 and 33% and one with inclusion rates of up to 50%, as well as a 2-year feeding trial with inclusion rates of 11 and 33% in male and female Wistar Han RCC rats by taking into account OECD Guidelines for the testing of chemicals and EFSA recommendations on the safety testing of whole-food/feed in laboratory animals. In all three trials, the NK603 maize, untreated and treated once with Roundup during its cultivation, and the conventional counterpart were tested. Differences between each test group and the control group were evaluated. Equivalence was assessed by comparing the observed difference to differences between non-GM reference groups in previous studies. In case of significant differences, whether the effects were dose-related and/or accompanied by changes in related parameters including histopathological findings was evaluated. It is concluded that no adverse effects related to the feeding of the NK603 maize cultivated with or without Roundup for up to 2 years were observed. Based on the outcome of the subchronic and combined chronic toxicity/carcinogenicity studies, recommendations on the scientific justification and added value of long-term feeding trials in the GM plant risk assessment process are presented.
Oxidative stress and sterile inflammation play roles in the induction and maintenance of metabolic syndrome (MetS). This study cohort included 170 females aged 40 to 45 years who were categorized ...according to the presentation of MetS components (e.g., central obesity, insulin resistance, atherogenic dyslipidemia, and elevated systolic blood pressure) as controls not presenting a single component (n = 43), those with pre-MetS displaying one to two components (n = 70), and females manifesting MetS, e.g., ≥3 components (n = 53). We analyzed the trends of seventeen oxidative and nine inflammatory status markers across three clinical categories. A multivariate regression of selected oxidative status and inflammatory markers on the components of MetS was performed. Markers of oxidative damage (malondialdehyde and advanced-glycation-end-products-associated fluorescence of plasma) were similar across the groups. Healthy controls displayed lower uricemia and higher bilirubinemia than females with MetS; and lower leukocyte counts, concentrations of C-reactive protein, interleukine-6, and higher levels of carotenoids/lipids and soluble receptors for advanced glycation end-products than those with pre-MetS and MetS. In multivariate regression models, levels of C-reactive protein, uric acid, and interleukine-6 were consistently associated with MetS components, although the impacts of single markers differed. Our data suggest that a proinflammatory imbalance precedes the manifestation of MetS, while an imbalance of oxidative status accompanies overt MetS. Further studies are needed to elucidate whether determining markers beyond traditional ones could help improve the prognosis of subjects at an early stage of MetS.
As part of a large human biomonitoring study, we conducted occupational monitoring in a glass fibre factory in Slovakia. Shopfloor workers (n = 80), with a matched group of administrators in the same ...factory (n = 36), were monitored for exposure to glass fibres and to polycyclic aromatic hydrocarbons (PAHs). The impact of occupational exposure on chromosomal aberrations, DNA damage and DNA repair, immunomodulatory markers, and the role of nutritional and lifestyle factors, as well as the effect of polymorphisms in metabolic and DNA repair genes on genetic stability, were investigated.
The (enzyme-modified) comet assay was employed to measure DNA strand breaks (SBs) and apurinic sites, oxidised and alkylated bases. Antioxidant status was estimated by resistance to H2O2-induced DNA damage. Base excision repair capacity was measured with an in vitro assay (based on the comet assay).
Exposure of workers to fibres was low, but still was associated with higher levels of SBs, and SBs plus oxidised bases, and higher sensitivity to H2O2. Multivariate analysis showed that exposure increased the risk of high levels of SBs by 20%. DNA damage was influenced by antioxidant enzymes catalase and glutathione S-transferase (measured in blood). DNA repair capacity was inversely correlated with DNA damage and positively with antioxidant status. An inverse correlation was found between DNA base oxidation and the percentage of eosinophils (involved in the inflammatory response) in peripheral blood of both exposed and reference groups. Genotypes of XRCC1 variants rs3213245 and rs25487 significantly decreased the risk of high levels of base oxidation, to 0.50 (p = 0.001) and 0.59 (p = 0.001), respectively.
Increases in DNA damage owing to glass fibre exposure were significant but modest, and no increases were seen in chromosome aberrations or micronuclei. However, it is of concern that even low levels of exposure to these fibres can cause significant genetic damage.
•Exposure of workers to glass fibres was associated with increased levels of DNA damage and higher sensitivity to H2O2.•DNA damage was influenced by catalase activity and glutathione S-transferase levels measured in peripheral blood.•XRCC1 variants rs3213245 and rs25487 were associated with a decrease in the risk of high DNA oxidation damage.•Glass fibre exposure did not affect the levels of chromosome aberrations or micronuclei in exposed workers.
Due to the growing number of applications of cadmium oxide nanoparticles (CdO NPs), there is a concern about their potential deleterious effects. The objective of our study was to investigate the ...effect of CdO NPs on the immune response, renal and intestine oxidative stress, blood antioxidant defence, renal fibrotic response, bone density and mineral content. Six-week-old female ICR mice were exposed to CdO NPs for 6 weeks by inhalation (particle size: 9.82 nm, mass concentration: 31.7 μg CdO/m3, total deposited dose: 0.195 μg CdO/g body weight). CdO NPs increased percentage of thymus CD3e+CD8a+ cells and moderately enhanced splenocyte proliferation and production of cytokines and chemokines. CdO NPs elevated pro-fibrotic factors (TGF-β2, α-SMA and collagen I) in the kidney, and concentrations of AGEs in the intestine. The ratio of GSH and GSSG in blood was slightly reduced. Exposure to CdO NPs resulted in 10-fold higher Cd concentration in tibia bones. No differences were found in bone mass density, mineral content, bone area values, bone concentrations of Ca, P, Mg and Ca/P ratio. Our findings indicate stimulation of immune/inflammatory response, oxidative stress in the intestine, starting fibrotic response in kidneys and accumulation of CdO NPs in bones of mice.
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•Six-week inhalation of CdO NPs resulted in significantly increased percentage of thymus CD3+CD8+ cells in mice.•Significantly higher concentrations of advanced glycation end-products were found in the intestine, but not in the kidney.•Moderate blood reduction of the ratio of reduced glutathione and oxidized glutathione was observed in CdO exposed mice.•Significant increase was found in kidney pro-fibrotic factors: TGF-β2, α-smooth muscle actin and collagen I.•In tibia, ten-fold higher Cd level was found, while Ca, P, Mg and other bone parameters (BMD, BMC, BA) were not changed.
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