Titanium Dioxide Nanoparticle (TiO2 NP) Induces Toxic Effects on LA-9 Mouse Fibroblast Cell Line.

BACKGROUND/AIMS: Titanium dioxide nanoparticles (TiO2 NPs) are extensively applied in the industry due to their photocatalytic potential, low cost, and considerably low toxicity. However, new unrelated physicochemical properties and the wide use of nanoparticles brought concern about their toxic effects. Thereby, we evaluated the cytotoxicity of a TiO2 NP composed of anatase and functionalized with sodium carboxylate ligands in a murine fibroblast cell line (LA-9). METHODS: Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS), and ATR-FTIR spectroscopy were applied to determine nanoparticle physicochemical properties. The cell viability (MTT assay) and clonogenic survival were analyzed in fibroblasts exposed to TiO2 NP (50, 150, and 250 µg/mL) after 24h. Moreover, oxidative stress, proinflammatory state, and apoptosis were evaluated after 24h. RESULTS: TiO2 NP characterization showed an increased hydrodynamic size (3.57 to 7.62 nm) due to solvent composition and a heterogeneity dispersion in water and cell culture media. Also, we observed a zeta potential increased from -20 to -11 mV in function of protein adsorption. TiO2 NP reduced fibroblast cell viability and induced ROS production at the highest concentrations (150 and 250 µg/mL). Moreover, TiO2 NP reduced the fibroblasts clonogenic survival at the highest concentration (250 µg/mL) on the 7th day after the 24h exposure. Nevertheless, TiO2 NP did not affect the fibroblast proinflammatory cytokines (IL-6 and TNF) secretion at any condition. Early and late apoptotic fibroblast cells were detected only at 150 µg/mL TiO2 NP after 24h. CONCLUSION: Probably, TiO2 NP photocatalytic activity unbalanced ROS production which induced apoptosis and consequently reduced cell viability and metabolic activity at higher concentrations.

IL-6 and IL-10 are associated with disease severity and higher comorbidity in adults with COVID-19.

AIM: COVID-19 pandemic has caused extensive burden on public life and health care worldwide. This study aimed to assess circulating levels of inflammatory cytokines in adult patients who were hospitalized with COVID-19 and stratified according to age (older or younger than 65 years) aiming to explore associations between these markers of inflammation and comorbidities. METHODS: This was a cross-sectional study of 142 COVID-19 patients consecutively admitted to the University Hospital of the Federal University of São Carlos, from July to October 2020. Sociodemographic data, chronic comorbidities, and baseline NEWS2 and SOFA for clinical deterioration were obtained at hospital admission. Serum levels of inflammatory cytokines were determined by flow cytometry. RESULTS: Older adults with COVID-19 had higher serum levels of IL-6 and IL-10 as compared to those under 65 years of age (p < 0.001 and p = 0.003, respectively). IL-10 was independently associated with age (p = 0.04) and severity of the disease (p = 0.05), whereas serum levels of IL-6 were not directly associated with age (p = 0.5). The comorbidity index seems to be the main responsible for this, being significantly associated with IL-6 levels among those aged 65 and over (p = 0.007), in addition to the severity of the disease. CONCLUSIONS: Higher serum levels of IL-6 and IL-10 are associated with the severity of the disease and a higher comorbidity index among adults aged 65 and over with COVID-19. This should raise awareness of the importance of comorbidity index, rather than age, during risk stratification.