A detoxikáló, immunológiai és nem immunológiai tényezők szerepe környezeti fizikai és kémiai faktorok által előidézett tüdőbetegségek pathomechanizmusában = The role of detoxifying, immunological and non-immunological factors in the pathomechanism of pulmonary diseases inducing by environmental physical and chemical agents

Egyszeri expozíció:Az azbesztpótló anyagok - kőgyapot, kerámiarost - előnytelenül befolyásolják a tüdő redox kapacitását, immunszupresszívek, amely alveoláris makrofágok és pneumocyták memebránjainak sérülésére vezethetők vissza. A nikkeloxid döntően az alveoláris pneumocytákat károsítja,amely összefüggésben áll a tüdő immunrendszerének szupressziójával, redox rendszerének károsításával, és a folyamatot károsan befolyásoló chemokinek termelődésével. A Stachybotris chartarum endo- és exotoxinjainak hatására a tüdő makrofágjaiban és alveoláris hámsejtjeiben csökkent a marker enzimek (sf, af) aktivitása, sérültek a sejtmembránok, amely miatt chemokinek szabadultak fel. Kombinált expozíciók:genotoxikus hatások:az azbesztpótló rostok: a kőgyapot, kerámiarost és alfa sugárzás megnövelte a DNS száltörések számát a kontrollhoz képest. Az NiO és a CdCl2 + alfa sugárzás hatására megnőtt a DNS lánc-töredezettség, különösen a II.pneumocytákban. Az apoptózis index az első napon 18%-ra emelkedett, majd a 6. hónap végére kontroll szintre csökkent. A CdCl2 a fokozott DNS száltöredezettségen kívül, megnövelte a mikronukleált sejtek számát. | Single exposure: the asbestos substituents - stone-wool, ceramic fibres - in consequence of toxic effects on cellular membranes, disadvantageously influenced the pulmonary redox capacity and showed immunosuppressive effects. NiO primarily damaged the alveolar pneumocytes which is connection with the suppression of pulmonary immune system, injuries of redox system and expression of chemokines. On the effect of endo-and exotoxins of Stachybotris chartarum, the activity of marker enzymes (acidic-,alkaline phosphatases) decreased, they gave rise to membrane damage causing expression of chemokines. Combined exposures:genotoxic effects: asbestos substituents+alpha radiation increased the number of DNA breaks. NiO and CdCl2 +alpha radiation increased the DNA breaks, especially in type II pneumocytes. Apotosis index increased to 18% by the first day, by the end of .6. month reduced to the control level. CdCl2 increased also the number of micronucleated cells and led to bystander effect. Biological effects: NiO+ceramic fibres: NiO did not influence the effect of ceramic fibres. Preliminary changes of malignancies did not develop(metaplasia)

Pharmacokinetics, biodistribution, and biosafety of PEGylated gold nanoparticles in vivo

Despite the obvious advantages of gold nanoparticles for biomedical applications, controversial and incomplete toxicological data hamper their widespread use. Here, we present the results from an in vivo toxicity study using gold nanoparticles coated with polyethylene glycol (PEG-AuNPs). The pharmacokinetics and biodistribution of PEG-AuNPs were examined in the rat's liver, lung, spleen, and kidney after a single i.v. injection (0.7 mg/kg) at different time intervals. PEG-AuNPs had a relatively long blood circulation time and accumulated primarily in the liver and spleen, where they remained for up to 28 days after administration. Increased cytoplasmic vacuolation in hepatocytes 24 h and 7 days after PEG-AuNPs exposure and apoptotic-like cells in white splenic pulp 24 h after administration has been detected, however, 28 days post-exposure were no longer observed. In contrast, at this time point, we identified significant changes in lipid metabolism, altered levels of liver injury markers, and elevated monocyte count, but without marked biological relevance. In blood cells, no DNA damage was present in any of the studied time intervals, with the exception of DNA breakage transiently detected in primary kidney cells 4 h post-injection. Our results indicate that the tissue accumulation of PEG-AuNPs might result in late toxic effects

Immune System and Environmental Xenobiotics - The Effect of Selected Mineral Fibers and Particles on the Immune Response

Medical genetic

Chapter Immune System and Environmental Xenobiotics - The Effect of Selected Mineral Fibers and Particles on the Immune Response

Medical genetic

Gold and titania nanoparticles accumulated in the body induce late toxic effects and alterations in transcriptional and miRNA landscape

The growing production of nanomaterials and their presence in consumer products raises fear about their impact on human health and the environment. Of particular concern are those nanomaterials that exhibit poor excretion and tend to accumulate in living organisms. Our study investigated the potential adverse biological effects of residual gold and titania nanoparticles (PEG-AuNPs and TiONPs) 28 days after a single intravenous administration in rats. To comprehensively assess the potential health hazard of these metal nanoparticles (MNP), toxicological and transcriptomic analyses were employed. The liver was the primary organ of the MNP deposition, causing a reduction in the relative liver weight compared to unexposed animals. Concurrently, changes in serum biomarkers indicative of hepatic dysfunction and hematological and immunological alternations were determined. Integrated transcriptomic analysis unveiled exposure-induced effects on the rats' lungs, liver, and kidneys. The hepatic tissue, particularly in PEG-AuNPs-exposed rats, exhibited a noteworthy prevalence of deregulated genes, with functional classification spanning lipid metabolism, cell cycle, and cell proliferation pathways. Although the number of deregulated miRNAs was relatively modest compared to mRNA expression changes, both types of MNPs deregulated miR-203a, associated with liver injury, and miR-18a-5p and miR-32-5p linked to kidney damage. This study underscores the imperative for a more exhaustive biosafety assessment of poorly soluble MNPs that tend to deposit in the body. Such investigations are crucial for delineating the potential risks of these nanomaterials and guiding the development of adequate safety measures in their production and usage

Immunotoxicity and genotoxicity testing of PLGA-PEO nanoparticles in human blood cell model

A human blood cell model for immunotoxicity and genotoxicity testing was used to measure the response to polylactic-co-glycolic acid (PLGA-PEO) nanoparticle (NP) (0.12, 3, 15 and 75 μg/cm² exposure in fresh peripheral whole blood cultures/isolated peripheral blood mononuclear cell cultures from human volunteers (n = 9-13). PLGA-PEO NPs were not toxic up to dose 3 μg/cm²; dose of 75 μg/cm² displays significant decrease in [³H]-thymidine incorporation into DNA of proliferating cells after 4 h (70% of control) and 48 h (84%) exposure to NPs. In non-cytotoxic concentrations, in vitro assessment of the immunotoxic effects displayed moderate but significant suppression of proliferative activity of T-lymphocytes and T-dependent B-cell response in cultures stimulated with PWM > CON A, and no changes in PHA cultures. Decrease in proliferative function was the most significant in T-cells stimulated with CD3 antigen (up to 84%). Cytotoxicity of natural killer cells was suppressed moderately (92%) but significantly in middle-dosed cultures (4 h exposure). On the other hand, in low PLGA-PEO NPs dosed cultures, significant stimulation of phagocytic activity of granulocytes (119%) > monocytes (117%) and respiratory burst of phagocytes (122%) was recorded. Genotoxicity assessment revealed no increase in the number of micronucleated binucleated cells and no induction of SBs or oxidised DNA bases in PLGA-PEO-treated cells. To conclude on immuno- and genotoxicity of PLGA-PEO NPs, more experiments with various particle size, charge and composition need to be done

Copper Oxide Nanoparticles Stimulate the Immune Response and Decrease Antioxidant Defense in Mice After Six-Week Inhalation

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 1.40×106 particles/cm3, geometric mean diameter 20.4 nm) on immune/inflammatory response and antioxidant defense in mice exposed to 32.5 µg CuO/m3 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