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1.
J Appl Toxicol ; 44(4): 595-608, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37968889

RESUMO

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.


Assuntos
Nanopartículas , Pneumonia , Feminino , Ratos , Masculino , Animais , Molibdênio/toxicidade , Molibdênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Pulmão , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Pneumonia/induzido quimicamente , Nanopartículas/toxicidade , Inflamação/patologia , Sulfetos/toxicidade
2.
Toxicol In Vitro ; 68: 104931, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32640262

RESUMO

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.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Dissulfetos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Molibdênio/administração & dosagem , Nanopartículas/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Modelos Biológicos , Tamanho da Partícula
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