Silver nanoparticles (AgNPs) are one of the most investigated metal-based nanomaterials. Their biocidal activity boosted their application in both diagnostic and therapeutic medical systems. It is therefore crucial to provide sound evidences for human-related safety of AgNPs. This study aimed to enhance scientific knowledge with regard to biomedical safety of AgNPs by investigating how their different surface properties affect human immune system. Methods: preparation, characterization and stability evaluation was performed for four differently coated AgNPs encompassing neutral, positive and negative agents used for their surface stabilization. Safety aspects were evaluated by testing interaction of AgNPs with fresh human peripheral blood mononuclear cells (hPBMC) by means of particle cellular uptake and their ability to trigger cell death, apoptosis and DNA damages through induction of oxidative stress and damages of mitochondrial membrane. Results: all tested AgNPs altered morphology of freshly isolated hPBMC inducing apoptosis and cell death in a dose- and time-dependent manner. Highest toxicity was observed for positively-charged and protein-coated AgNPs. Cellular uptake of AgNPs was also dose-dependently increased and highest for positively charged AgNPs. Intracellularly, AgNPs induced production of reactive oxygen species (ROS) and damaged mitochondrial membrane. Depending on the dose, all AgNPs exhibited genotoxic potential. Conclusions: this study provides systematic and comprehensive data showing how differently functionalized AgNPs may affect the human immune system. Presented results are a valuable scientific contribution to safety assessment of nanosilver-based blood-contacting medical products.
1 April 2019 in Pulmonary Pharmacology & Therapeutics
A freely available “in vitro dosimetry” web application is presented enabling users to predict the concentration of nanomaterials reaching the cell surface, and therefore available for attachment and internalization, from initial dispersion concentrations. The web application is based on the distorted grid (DG) model for the dispersion of engineered nanoparticles (NPs) in culture medium used for in vitro cellular experiments, in accordance with previously published protocols for cellular dosimetry determination. A series of in vitro experiments for six different NPs, with Ag and Au cores, are performed to demonstrate the convenience of the web application for calculation of exposure concentrations of NPs. Our results show that the exposure concentrations at the cell surface can be more than 30 times higher compared to the nominal or dispersed concentrations, depending on the NPs’ properties and their behavior in the cell culture medium. Therefore, the importance of calculating the exposure concentration at the bottom of the cell culture wells used for in vitro arrays, i.e., the particle concentration at the cell surface, is clearly presented, and the tool introduced here allows users easy access to such calculations. Widespread application of this web tool will increase the reliability of subsequent toxicity data, allowing improved correlation of the real exposure concentration with the observed toxicity, enabling the hazard potentials of different NPs to be compared on a more robust basis.
Olive leaves are the richest source of phenolic compounds, particularly oleuropein, which has many beneficial effects on human health. This study compares the effect of three extraction techniques: ultrasonic-solvent extraction, microwave-assisted extraction, and supercritical CO2 extraction of freeze-dried wild olive leaves (Olea europea subps. oleaster, Hoffmanns. & Link) on oleuropein concentration in obtained extracts. The extract with the highest concentration of oleuropein was obtained after low-frequency ultrasound solvent extraction (WOLE-S) (71.97 µg/mL). Oleuropein from that extract showed low stability after simulated gastric digestion with human gastric juices (35.66%) and high stability after 60 min of intestinal phase (65.97%). The highest antiproliferative activity of WOLE-S and pure oleuropein was detected against T24 cancer cells. The antiproliferative activity of WOLE-S against MD-MBA-123, A549, and A1235 cells was moderate, while the activity of oleuropein was high. WOLE-S significantly down-regulated the expression of IL-6 in A549 cells, indicating a possible anti-inflammatory effect in lung cancer cells. The expression of IL-8 was slightly reduced by treating the cells with WOLE-S, while the expression of IL-10 was not altered by the treatment with WOLE-S or oleuropein.
Inorganic pollutants released into aquatic habitats by human activity, such as metals and radionuclides, present a serious threat to biodiversity and ecosystem health. Various biomonitoring efforts were established to track their release and environmental concentrations, including sampling of bioindicator species, which can accumulate these pollutants and facilitate their detection. Dragonflies (order Odonata) are considered valuable bioindicator organisms due to their relative longevity and predatory lifestyle, and have been used to assess environmental concentrations of a wide variety of pollutants. However, there is a lack of systematic effort to determine which elements are likely to be accumulated in dragonfly tissue from surrounding water, and how the concentrations of accumulated materials correlate to their environmental concentrations. In this review, studies that used dragonflies as bioindicators for metals and radionuclides in aquatic environments were analyzed, and bioaccumulation factors for each element were calculated. The highest bioaccumulation factors were obtained for U and Cs, elements with the highest numbers of bioaccumulation studies were Hg and Cu, and Se was the most consistently accumulated element in analyzed studies. The results have shown that dragonflies are suitable bioindicator organisms for a variety of different radioactive and non-radioactive elements, and calculated bioaccumulation factors provide a link between their presence in dragonfly tissue and the environmental concentrations in their habitats.