Biological effects of molybdenum(IV) sulfide nanoparticles and microparticles in the rat after repeated intratracheal administration.

In this study, molybdenum(IV) sulfide (MoS2 ) nanoparticles (97 ± 32 nm) and microparticles (1.92 ± 0.64 µm) stabilized with poly (vinylpolypyrrolidone) (PVP) were administered intratracheally to male and female rats (dose of 1.5 or 5 mg/kg bw), every 14 days for 90 days (seven administrations in total). Blood parameters were assessed during and at the end of the study (hematology, biochemistry including glucose, albumins, uric acid, urea, high density lipoprotein HDL, total cholesterol, triglycerides, aspartate transaminase, and alanine transaminase ALT). Bronchoalveolar lavage fluid (BALF) analyses included cell viability, biochemistry (total protein concentration, lactate dehydrogenase, and glutathione peroxidase activity), and cytokine levels (tumor necrosis factor α, TNF-α, macrophage inflammatory protein 2-alpha, MIP-2, and cytokine-induced neutrophil chemoattractant-2, CINC-2). Tissues were subjected to routine histopathological and electron microscopy (STEM) examinations. No overt signs of chronic toxicity were observed. Differential cell counts in BALF revealed no significant differences between the animal groups. An increase in MIP-2 and a decrease in TNF-α were observed in BALF in the exposed males. The histopathological changes in the lung evaluated according to a developed classification system (based on severity of inflammation, range 0-4, with 4 indicating the most severe changes) showed average histopathological score of 1.33 for animals exposed to nanoparticles and microparticles at the lower dose, 1.72 after exposure to nanoparticles at the higher dose, and 2.83 for animals exposed to microparticles at the higher dose. In summary, it was shown that nanosized and microsized MoS2 can trigger dose-dependent inflammatory reactions in the lungs of rats after multiple intratracheal instillation irrespective of the animal sex. Some evidence indicates a higher lung pro-inflammatory potential of the microform.

Comparative analysis of biological effects of molybdenum(IV) sulfide in the form of nano- and microparticles on human hepatoma HepG2 cells grown in 2D and 3D models.

Significance of MoS2 nanoparticles as a lubricant or drug carriers indicates the need to assess their safety. In the study we analyzed the effects of MoS2 nano- and microparticles and their internalization in vitro, using 2D and 3D culture models of human hepatoma HepG2 cell line. MoS2 micro- and nanoparticles were characterized with high resolution electron microscopy (HR-SEM), X-ray diffraction (XRD) and Energy Dispersive X-Ray Spectroscopy (EDS). The cells were exposed to a range of concentrations of the nano-and microparticles suspensions (maximum of 250 µg/mL) for 72 h. Cell viability was assessed using WST-1 reduction test and LDH release assay. Particle internalization was analyzed using scanning transmission electron microscopy (STEM). The nanoparticles were internalized into the 2D and 3D cultured cells, in spheroids more efficiently into the outer layer. For microparticles mainly particles of less than 1 µm in diameter underwent internalization. This process, however, did not affect cell viability as measured with the WST-1 and LDH assays. STEM observation showed well preserved integrity of the cell membrane and no apparent cytotoxic effect. Although the particles seemed to be safely sequestered in vacuoles or the cytoplasm, their fate and eventual biological effects are not certain and deserve further studies.

Assessment of acute toxicological effects of molybdenum(IV) disulfide nano- and microparticles after single intratracheal administration in rats.

Despite growing applications of molybdenum(IV) sulfide (MoS2) nano- and microparticles in their capacity as lubricants, data available on their safety are scarce. In this study the effect of MoS2 nano- and microparticles after single intratracheal instillation in rats has been analyzed. MoS2 suspensions were administered at the dose of 1.5 or 5 mg MoS2/kg body weight. The analysis after 24 h and 7 days included: blood biochemical parameters, hematological parameters, bronchoalveolar lavage fluid (BALF) parameters with selected cytokines, a comet assay and histopathological examination. In the BALF cells isolated from animals exposed to both forms, numerous macrophages loaded with particles were observed. The hematological and biochemical parameters analyzed 24 h or 7 days after the exposure to both forms did not show any biologically meaningful changes. Comet assay results showed no genotoxic effect. The histopathological analysis of the lungs revealed inflammatory changes in the respiratory system of the treated animals, slightly stronger for the microsized form. The deposits of particles observed in the lung tissue up to 7 days after the instillation indicate their easy penetration through the epithelium and prolonged clearance. Concluding, no meaningful acute systemic effects were observed, however some pathological changes were noted in the lung tissue.

Cytotoxic effects in transformed and non-transformed human breast cell lines after exposure to silver nanoparticles in combination with selected aluminium compounds, parabens or phthalates.

This study was undertaken to assess cytotoxic effects of selected aluminium compounds, parabens and phthalates in combination with silver nanoparticles (AgNP, 15 and 45 nm by STEM, Ag15 and Ag45, respectively) on cell lines of the human breast epithelium, normal (MCF-10A) and transformed (MDA-MB-231 and MCF-7). Combination indices were the most spectacular at effective concentrations (ED) inducing 25 % decrease in viability for the combinations of Ag15 with AlCl3 for MDA-MB-231 cells or aluminium zirconium tetrachlorohydrex Gly (AlZr) for MCF-10A and MCF-7 cells, where rather strong antagonism was revealed. As the ED values increased, those effects were enhanced (e.g. Ag15+AlCl3 for MDA-MB-231) or reversed into synergism (e.g. Ag15+AlZr for MCF-7). Another strong effect was observed for aluminium chloride hydroxide, which increasing ED, induced synergistic effect with both Ag15 and Ag45 on MCF-10A cells. Another interesting synergistic effect was observed for DBPh, but only in combination with Ag45 on MCF-10A and MCF-7. The results on cytotoxicity, cell cycle and oxidative stress induction indicate complex response of the cell lines to combined treatment with silver nanoparticles and the chemicals, which were influenced by diverse factors, such as physico-chemical characteristics of AgNP, method of their synthesis, concentrations used, and finally cell type.

Genotoxic effects in transformed and non-transformed human breast cell lines after exposure to silver nanoparticles in combination with aluminium chloride, butylparaben or di-n-butylphthalate.

In the present study genotoxic effects after combined exposure of human breast cell lines (MCF-10A, MCF-7 and MDB-MB-231) to silver nanoparticles (AgNP, citrate stabilized, 15 and 45nm by STEM, Ag15 and Ag45, respectively) with aluminium chloride, butylparaben, or di-n-butylphthalate were studied. In MCF-10A cells exposed for 24h to Ag15 at the concentration of 23.5µg/mL a statistically significant increase in DNA damage in comet assay (SSB) was observed. In the presence of the test chemicals the genotoxic effect was decreased to a level comparable to control values. In MCF-7 cells a significant increase in SSB level was observed after exposure to Ag15 at 16.3µg/mL. The effect was also diminished in the presence of the three test chemicals. In MDA-MB-231 cells no significant increase in SSB was observed, however increased level of oxidative DNA damage (incubation with Fpg enzyme) was observed after exposure to combinations of both AgNP with aluminium chloride. No increase in micronuclei formation was observed in neither cell line after the single nor combined treatments. Our results point to a low risk of increased genotoxic effects of AgNP when used in combination with aluminium salts, butylparaben or di-n-butylphthalate in consumer products.