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

• Published in: Journal of applied toxicology Vol. 44; no. 4; pp. 595 - 608
• Main Authors: Sobańska, Z., Sitarek, K., Gromadzińska, J., Świercz, R., Szparaga, M., Domeradzka‐Gajda, K., Kowalczyk, K., Zapór, L., Wąsowicz, W., Grobelny, J., Ranoszek‐Soliwoda, K., Tomaszewska, E., Celichowski, G., Roszak, J., Stępnik, M.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.04.2024
• Subjects: Alanine; Alanine transaminase; Animals; Aspartate transaminase; Biochemistry; Biological effects; Bronchoalveolar Lavage Fluid; Bronchus; Cell viability; Cholesterol; Chronic toxicity; Cytokines; Cytokines - metabolism; Electron microscopy; Exposure; Female; Glutathione; Glutathione peroxidase; Hematology; High density lipoprotein; Inflammation; Inflammation - pathology; intratracheal instillation; L-Lactate dehydrogenase; Lactate dehydrogenase; Lavage; Leukocytes (neutrophilic); Lung; Lungs; Macrophage inflammatory protein; Macrophage inflammatory protein 2; Male; Microparticles; Molybdenum; Molybdenum - metabolism; Molybdenum - toxicity; Molybdenum disulfide; molybdenum(IV) sulfide; Nanoparticles; Nanoparticles - toxicity; Peroxidase; Pneumonia - chemically induced; Proteins; rat; Rats; Sulfides; Sulfides - toxicity; Trachea; Triglycerides; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Urea; Uric acid; molybdenum(IV) sulfide; microparticles; intratracheal instillation; nanoparticles; rat
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.4563

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. Molybdenum(IV) sulfide (MoS2) nanoparticles and microparticles administered intratracheally to rats (1.5 or 5 mg/kg bw), every 14 days for 90 days, induced no overt signs of systemic chronic toxicity. An increase in MIP‐2 and a decrease in TNF‐α were observed in BALF in the exposed males. Based on histopathological examination, nanosized and microsized MoS2 can trigger dose‐dependent inflammatory reactions in the lungs of rats after multiple intratracheal instillations, with a slightly higher lung pro‐inflammatory potential of the microform.