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.
- Klíčová slova
- Cadmium oxide nanoparticles, Inhalation, Mice, Nanotoxicology,
- MeSH
- aplikace inhalační MeSH
- buněčná imunita účinky léků MeSH
- cytokiny metabolismus MeSH
- fibróza chemicky indukované MeSH
- kovové nanočástice aplikace a dávkování toxicita MeSH
- ledviny účinky léků patologie MeSH
- lymfatické uzliny účinky léků MeSH
- myši inbrední ICR MeSH
- oxidační stres účinky léků MeSH
- oxidy aplikace a dávkování toxicita MeSH
- slezina účinky léků MeSH
- sloučeniny kadmia aplikace a dávkování toxicita MeSH
- střeva účinky léků MeSH
- thymus účinky léků MeSH
- tibie účinky léků MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cadmium oxide MeSH Prohlížeč
- cytokiny MeSH
- oxidy MeSH
- sloučeniny kadmia MeSH
Innovative nanotechnology aims to develop particles that are small, monodisperse, smart, and do not cause unintentional side effects. Uniform magnetic Fe3O4 nanoparticles (12 nm in size) were prepared by thermal decomposition of iron(III) oleate. To make them colloidally stable and dispersible in water and cell culture medium, they were modified with phosphonic acid- (PA) and hydroxamic acid (HA)-terminated poly(ethylene glycol) yielding PA-PEG@Fe3O4 and HA-PEG@Fe3O4 nanoparticles; conventional γ-Fe2O3 particles were prepared as a control. Advanced techniques were used to evaluate the properties and safety of the particles. Completeness of the nanoparticle coating was tested by real-time polymerase chain reaction. Interaction of the particles with primary human peripheral blood cells, cellular uptake, cytotoxicity, and immunotoxicity were also investigated. Amount of internalized iron in peripheral blood mononuclear cells was 72, 38, and 25 pg Fe/cell for HA-PEG@Fe3O4, γ-Fe2O3, and PA-PEG@Fe3O4, respectively. Nanoparticles were localized within the cytoplasm and in the extracellular space. No cytotoxic effect of both PEGylated nanoparticles was observed (0.12-75 μg/cm2) after 24 and 72-h incubation. Moreover, no suppressive effect was found on the proliferative activity of T-lymphocytes and T-dependent B-cell response, phagocytic activity of monocytes and granulocytes, and respiratory burst of phagocytes. Similarly, no cytotoxic effect of γ-Fe2O3 particles was observed. However, they suppressed the proliferative activity of T-lymphocytes (75 μg/cm2, 72 h) and also decreased the phagocytic activity of monocytes (15 μg/cm2, 24 h; 3-75 μg/cm2, 72 h). We thus show that newly developed particles have great potential especially in cancer diagnostics and therapy.
- Klíčová slova
- Iron oxide nanoparticles, PCR inhibition, cell interaction and uptake, cytotoxicity and immunotoxicity, human peripheral blood leucocytes,
- MeSH
- cytokiny metabolismus MeSH
- fagocytóza účinky léků imunologie MeSH
- kultivované buňky MeSH
- kyseliny fosforité chemie MeSH
- kyseliny hydroxamové chemie MeSH
- leukocyty mononukleární účinky léků imunologie patologie MeSH
- lidé MeSH
- magnetické nanočástice chemie toxicita MeSH
- nanomedicína metody MeSH
- polyethylenglykoly chemie MeSH
- povrchové vlastnosti MeSH
- proliferace buněk účinky léků MeSH
- respirační vzplanutí účinky léků imunologie MeSH
- velikost částic MeSH
- viabilita buněk účinky léků imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cytokiny MeSH
- kyseliny fosforité MeSH
- kyseliny hydroxamové MeSH
- magnetické nanočástice MeSH
- phosphonic acid MeSH Prohlížeč
- polyethylenglykoly MeSH
The exceptionally high cellular uptake of gold nanorods (GNRs) bearing cationic surfactants makes them a promising tool for biomedical applications. Given the known specific toxic and stress effects of some preparations of cationic nanoparticles, the purpose of this study was to evaluate, in an in vitro and in vivo in mouse, the potential harmful effects of GNRs coated with (16-mercaptohexadecyl)trimethylammonium bromide (MTABGNRs). Interestingly, even after cellular accumulation of high amounts of MTABGNRs sufficient for induction of photothermal effect, no genotoxicity (even after longer-term accumulation), induction of autophagy, destabilization of lysosomes (dominant organelles of their cellular destination), alterations of actin cytoskeleton, or in cell migration could be detected in vitro. In vivo, after intravenous administration, the majority of GNRs accumulated in mouse spleen followed by lungs and liver. Microscopic examination of the blood and spleen showed that GNRs interacted with white blood cells (mononuclear and polymorphonuclear leukocytes) and thrombocytes, and were delivered to the spleen red pulp mainly as GNR-thrombocyte complexes. Importantly, no acute toxic effects of MTABGNRs administered as 10 or 50 μg of gold per mice, as well as no pathological changes after their high accumulation in the spleen were observed, indicating good tolerance of MTABGNRs by living systems.
- Klíčová slova
- Autophagy, Genotoxicity, Lysosomal stress, Plasmonic photothermal effect, Spleen, Thrombocytes,
- MeSH
- autofagie účinky léků MeSH
- kvartérní amoniové sloučeniny metabolismus MeSH
- lidé MeSH
- lyzozomy účinky léků metabolismus MeSH
- mezenchymální kmenové buňky cytologie účinky léků MeSH
- mikrofilamenta účinky léků metabolismus MeSH
- mutageny toxicita MeSH
- myši inbrední C57BL MeSH
- nádorové buněčné linie MeSH
- nanotrubičky chemie toxicita ultrastruktura MeSH
- podocyty účinky léků metabolismus MeSH
- pohyb buněk účinky léků MeSH
- poškození DNA MeSH
- slezina účinky léků patologie MeSH
- sulfhydrylové sloučeniny metabolismus MeSH
- tkáňová distribuce MeSH
- trombocyty účinky léků patologie ultrastruktura MeSH
- zlato metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- (16-mercaptohexadecyl)trimethylammonium bromide MeSH Prohlížeč
- kvartérní amoniové sloučeniny MeSH
- mutageny MeSH
- sulfhydrylové sloučeniny MeSH
- zlato MeSH
Slovakia is characterised by an unusually high number of patients affected by genetic Creutzfeldt-Jakob disease (CJD) with E200K mutation at the PRNP gene. Penetrance of the mutation is incomplete (59%). Therefore, for the onset of the clinical manifestation, an influence of other endo- or exogenous factors could not be excluded. Experimental data suggest that copper and manganese levels may play an important role in the pathogenesis of prion diseases. The highest number of Slovak genetic CJD patients originates from Orava - the northern region of central Slovakia. Manganese is a dominant pollutant in Orava. The objective of this study was to clarify a possible exogenous influence of environmental Mn/Cu imbalance on the CJD clustering. Mn and Cu levels were analysed in the brain tissue of genetic CJD cases (from Orava and from control regions of Slovakia), as well as of sporadic CJD patients and controls. Analyses demonstrate i) significantly higher Mn level in focally accumulated, "clustering" genetic CJD cases in comparison to all other groups, ii) Cu status differences between compared groups were without statistical significance; decreased concentrations were found in genetic cases from extrafocal genetic CJD areas, iii) Mn/Cu ratios were increased in all CJD groups in comparison to controls. Metal ratios in clustering gCJD cases were significantly higher in comparison to sporadic cases and also to controls, but not to the extrafocal genetic CJD subgroup. These results indicate that more important than increasing Mn level in pathogenesis of CJD appears to be the role of the Mn/Cu imbalance in the CNS. The imbalance observed in the cluster of genetic CJD cases is probably a result of both: the excessive environmental Mn level and the disturbance of Mn/Cu ratios in the Orava region. Presented findings indicate an environmental Mn/Cu imbalance as a possible exogenous CJD risk co-factor which may, in coincidence with endogenous (genetic) CJD risk, contribute to the focal accumulation (cluster) of genetic CJD in Slovakia.
- MeSH
- Creutzfeldtova-Jakobova nemoc epidemiologie etiologie genetika MeSH
- lidé MeSH
- mangan škodlivé účinky analýza MeSH
- měď škodlivé účinky analýza MeSH
- mozek - chemie MeSH
- polymerázová řetězová reakce MeSH
- polymorfismus genetický MeSH
- prionová bílkovina MeSH
- priony genetika MeSH
- rizikové faktory MeSH
- shluková analýza MeSH
- studie případů a kontrol MeSH
- vystavení vlivu životního prostředí škodlivé účinky MeSH
- zeměpis MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Slovenská republika epidemiologie MeSH
- Názvy látek
- mangan MeSH
- měď MeSH
- prionová bílkovina MeSH
- priony MeSH
- PRNP protein, human MeSH Prohlížeč
Cadmium is a toxic element ubiquitous in the environment, which damages biological systems in various ways. The major source of cadmium exposure is food. High cadmium content in the soil leads to high cadmium concentrations in certain plants such as grains (above all surface layers and germs), oil or non-oil seeds, fruit and vegetables. These food commodities are the crucial components of a vegetarian nutrition. Blood cadmium concentrations were measured in two non-smoking population groups: the vegetarian group (n = 80) and the non-vegetarian (control) group of general population on traditional mixed diet (n = 84). The significantly higher blood cadmium content (1.78 +/- 0.22 vs. 0.45 +/- 0.04 microg/l) was measured in vegetarian group. Healthy risk values > 5 microg/l were found in 6 vegetarians vs. no non-vegetarian. The highest cadmium concentration (3.15 +/- 0.77 microg/l) was measured in vegan subgroup (plant food only, n = 10) and that value decreased with increasing animal food consumption (1.75 +/- 0.36 microg/l, lactovegetarian and lactoovovegetarian subgroup/added dairy products and eggs, n = 41/, 1.34 +/- 0.21 microg/I, semivegetarian subgroup /as a previous subgroup and added white meat, n = 291). Risk vegetarians vs. non-risk vegetarians consume significantly higher amounts of whole grain products, grain sprouts and oil seeds. Blood cadmium content is directly influenced by age (r = 0.32, p < 0.001), by whole grain product intake (r = 0.66, p < 0.001) and by duration of vegetarianism (r = 0.5, p < 0.001). Oxidative stress plays a major role in chronic cadmium induced hepatic and renal toxicity as well as in other consequences of cadmium injuries. Vegetarians have significantly higher plasma concentrations of natural antioxidants. The sufficient antioxidative protection against cadmium induced free radical formation in vegetarians may inhibit the harmful effects of greater cadmium intake from plant food.
- MeSH
- dieta vegetariánská škodlivé účinky MeSH
- dospělí MeSH
- jedlá semena MeSH
- kadmium krev MeSH
- kontaminace potravin * MeSH
- lidé středního věku MeSH
- lidé MeSH
- oleje rostlin MeSH
- semena rostlinná MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- kadmium MeSH
- oleje rostlin MeSH
