Nanotoxicology最新文献

Although copper is an indispensable trace metal for biological functions, its excess exposure causes hazardous effects on health. Copper in the form of nanoparticles (CuNPs) is widely used at present and therefore, the living organism is at continuous risk of its adverse effect. The prolonged treatment of CuNPs has not been evaluated yet on the male reproductive system. To demonstrate the combined adverse effects and the mechanism of copper nanoparticles (CuNPs), three doses of CuNPs, 10, 100 and 200 mg/kg were orally given to mice for 70 days. The present study demonstrated that CuNPs decreased the sperm quality parameters, male circulating hormones, induces testicular damages, increased oxidative stress, apoptosis, decreases antioxidant enzymes, germ cell proliferation, and increases the expression of 8-oxoguanine DNA glycosylase-1 (OGG1), apelin receptor (APJ) as well. CuNPs also down-regulated the expression of AR and Erα in the testis. These results suggest that CuNPs manifested their adverse effect on testis via modulating steroid and cytokine (apelin) receptors. The adverse effect of testis was most pronounced at the highest dose (200 mg/kg) of CuNPs, however, other doses show a less toxic effect on various parameters. In conclusion, results indicated that CuNPs may impair spermatogenesis via oxidative stress-mediated DNA damage and germ cell apoptosis at high doses.

The demand for nutrients and new technologies has increased with population growth. The agro-technological revolution with metal oxide engineered nanoparticles (MeOx ENPs) has the potential to reform the resilient agricultural system while maintaining the security of food. When utilized extensively, MeOx ENPs may have unintended toxicological effects on both target and non-targeted species. Since limited information about nanopesticides' pernicious effects is available, in silico modeling can be done to explore these issues. Hence, in the present work, we have applied computational modeling to explore the influence of metal oxide nanoparticles on the toxicity of bronchial epithelial (BEAS-2B) and murine myeloid (RAW 264.7) cells to bridge the data gap relating to the toxicity of MeOx NPs. Initially, partial least squares (PLS) regression models were developed applying the Small Dataset Modeler software (http://teqip.jdvu.ac.in/QSAR_Tools/DTCLab/) using four datasets having effective concentration (EC₅₀%) as the endpoints and employing only periodic table descriptors. To further explore the predictions, we applied a read-across approach using the descriptors selected in the QSAR models. Also, the inter-endpoint cytotoxicity relationship modeling (quantitative toxicity-toxicity relationship or QTTR) was conducted. It was found that the result obtained by nano-read-across provided a similar level of accuracy as provided by QSAR. The information derived from the PLS models of both the cell lines suggested that metal cation formation, and bond-forming capacity influence the toxicity whereas the presence of metal has an influential impact on the ecotoxicological effects. Thus, it is feasible to design safe nanopesticides that could be more effective than conventional analogs.

Multiwalled carbon nanotubes (MWCNTs) are currently widely used and are expected to be used as drug carriers and contrast agents in clinical practice. Previous studies mainly focused on their lung toxicity; therefore, their effects on the vascular endothelium are unclear. In this study, a human angiogenesis array was used to determine the effect of MWCNTs on the expression profile of angiogenic factors in endothelial cells and to clarify the role of vascular endothelial growth factor (VEGF) in MWCNT-induced endothelial cell injury at the cellular and animal levels. The results indicated that MWCNTs (20-30 nm and 30-50 nm) could enter endothelial cells and disrupt human umbilical vein endothelial cell (HUVECs) activity in a concentration-dependent manner. MWCNTs disrupted the tube formation ability and cell migration function of HUVECs. The results from a Matrigel Plug experiment in mice showed that angiogenesis in the MWCNT experimental group was significantly reduced. The results of a protein chip analysis indicated that VEGF expression in the MWCNT treatment group was decreased, a finding that was validated by ELISA results. The protein expression levels of AKT and eNOS in the MWCNT treatment group were significantly decreased; the administration of recombinant VEGF significantly alleviated the migration ability and tube formation ability of endothelial cells injured by MWCNTs, upregulated the protein expression of AKT and eNOS, and increased the number of neovascularization in mice in the MWCNT treatment group. This study demonstrated that MWCNTs affect angiogenesis via the VEGF-Akt-eNOS axis which can be rescued by VEGF endothelial treatment.

Currently, copper nanoparticles are used in various sectors of industry, agriculture, and medicine. To understand the effects induced by these nanoparticles, it is necessary to assess the environmental risk and safely expand their use. In this study, we evaluated the toxicity of copper oxide (nCuO) nanoparticles in Danio rerio adults, their distribution/concentration, and chemical form after exposure. This last assessment had never been performed on copper-exposed zebrafish. Such evaluation was done through the characterization of nCuO, acute exposure tests and analysis of distribution and concentration by microstructure X-ray fluorescence spectroscopy (µ-XRF) and atomic absorption spectroscopy (GF-AAS). Synchrotron X-ray absorption spectroscopy (XAS) was performed to find out the chemical form of copper in hotspots. The results show that the toxicity values of fish exposed to nCuO were 2.4 mg L^-1 (25 nm), 12.36 mg L^-1 (40 nm), 149.03 mg L^-1 (80 nm) and 0.62 mg L^-1 (CuSO₄, used as a positive control). The total copper found in the fish was in the order of mg kg^-1 and it was not directly proportional to the exposure concentration; most of the copper was concentrated in the gastric system. However, despite the existence of copper hotspots, chemical transformation of CuO into other compounds was not detected.

While the various physicochemical properties of engineered nanomaterials influence their toxicities, their understanding is still incomplete. A predictive framework is required to develop safe nanomaterials, and a Bayesian network (BN) model based on adverse outcome pathway (AOP) can be utilized for this purpose. In this study, to explore the applicability of the AOP-based BN model in the development of safe nanomaterials, a comparative study was conducted on the change in the probability of toxicity pathways in response to changes in the dimensions and surface functionalization of multi-walled carbon nanotubes (MWCNTs). Based on the results of our previous study, we developed an AOP leading to cell death, and the experimental results were collected in human liver cells (HepG2) and bronchial epithelium cells (Beas-2B). The BN model was trained on these data to identify probabilistic causal relationships between key events. The results indicated that dimensions were the main influencing factor for lung cells, whereas -OH or -COOH surface functionalization and aspect ratio were the main influencing factors for liver cells. Endoplasmic reticulum stress was found to be a more sensitive pathway for dimensional changes, and oxidative stress was a more sensitive pathway for surface functionalization. Overall, our results suggest that the AOP-based BN model can be used to provide a scientific basis for the development of safe nanomaterials.

With the wide application of nanometer materials in daily life, people pay more attention to the potential toxicity of nanoparticles to human fetal development once the nanoparticles are absorbed into the human body during pregnancy. However, there was no directly solid evidence for ZnO NPs-caused congenital heart defects. Hence, we investigated the effect of ZnO NPs exposure on early cardiogenesis using the chicken/mouse embryo models. First, we showed ZnO NPs reduced H9c2 cell viability in a dose- and time-dependent manner, while cell autophagy was significantly activated too on the same pattern. During early cardiogenesis, ZnO NPs exposure increased the chance of heart tube malformation, while precardiac cell apoptosis rises in the phenotype of closure defect and Bifida. The hypertrophy was also observed in late-stage chicken/mouse survival embryos exposed to ZnO NPs. Apart from cell apoptosis, high-dose ZnO NPs exposure led to massive programmed necrosis, and further experiments verified that ferroptosis remained primarily in ZnO NPs-induced programmed necrosis. We also revealed that the toxicology of low-dose ZnO NPs was mainly featured in the changes of expressions of key genes instead of causing precardiac cell death. MYL2 and CSRP3 could work as the downstream molecules of the above key genes in the context of ZnO NPs exposure to early cardiogenesis based on RNA sequencing. Taken together, this study for the first time revealed the potential risk of heart tube malformation induced by ZnO NPs exposure through different cellular mechanisms, which depended on low- or high-dose ZnO NPs.

The study concerns the influence of graphene monolayer, as a 2 D platform, on cell viability, cytoskeleton, adhesions sites andmorphology of mitochondria of keratinocytes (HaCaT) under static conditions. Based on quantitative and immunofluorescent analysis, it could be stated that graphene substrate does not cause any damage to membrane or disruption of other monitored parameters. Spindle poles and cytokinesis bridges indicating proliferation of cells on this graphene substrate were detected. Moreover, the keratinocyte migration rate on the graphene substrate was comparable to control glass substrate when the created wound was completely closed after 38 hours. HaCaT morphology and viability were also assessed under dynamic conditions (lab on a chip - micro scale). For this purpose, microfluidic graphene system was designed and constructed. No differences as well as no anomalies were observed during cultivation of these cells on the graphene or glass substrates in relation to cultivation conditions: static (macro scale) and dynamic (micro scale). Only natural percentage of dead cells was determined using different methods, which proved that the graphene as the 2 D platform is cytocompatible with keratinocytes. The obtained results encourage the use of the designed lab on a chip system in toxicity testing of graphene also on other cells and further research on the use of graphene monolayers to produce bio-bandages for skin wounds in animal tests.

Metal oxide nanoparticles (MONPs) are commonly found in the aquatic and terrestrial systems as chemical mixtures. Assessment of cytotoxicity associated with single and combination of MONPs can truly identify the concerned environmental risk. Thus, using Escherichia coli as a test model, in vitro cytotoxicity of 6 single MONPs, 15 binary and 20 tertiary mixtures with equitoxic ratios was evaluated following standard bioassay protocols. Assessment of oxidative stress suggested that the production of reactive oxygen species (ROS) was negligible, and the release of metal zinc ions played an important role in the toxicity of MONP mixtures. From our experimental data points, seven quantitative structure-activity relationships (QSARs) models were developed to model the cytotoxicity of these MONPs, based on our created periodic table-based descriptors and experimentally analyzed Zeta-potential. Two strategic approaches i.e. pharmacological and mathematical hypotheses were considered to identify the mixture descriptors pool for modeling purposes. The stringent validation criteria suggested that the model (Model M4) developed with mixture descriptors generated by square-root mole contribution outperformed the other six models considering validation criteria. While considering the pharmacological approach, the 'independent action' generated descriptor pool offered the best model (Model M2), which firmly confirmed that each MONP in the mixture acts through 'independent action' to induce cytotoxicity to E. coli instead of fostering an additive, antagonistic or synergistic effect among MONPs. The total metal electronegativity in a specific metal oxide relative to the number of oxygen atoms and metal valence was associated with a positive contribution to cytotoxicity. At the same time, the core count, which gives a measure of molecular bulk and Zeta potential, had a negative contribution to cytotoxicity.

Climate change events, such as drought, are increasing and soil bacteria can be severely affected. Moreover, the accumulation of emerging pollutants is expected to rapidly increase, and their impact on soil organisms, their interactions, and the services they provide is poorly known. The use of graphene oxide (GO) has been increasing due to its enormous potential for application in several areas and it is expected that concentration in soil will increase in the future, potentially causing disturbances in soil microorganisms not yet identified.Here we show the effects that GO nanosheets can cause on soil bacteria, in particular those that promote plant growth, in control and 10% polyethylene glycol (PEG) conditions. Low concentrations of GO nanosheets did not affect the growth of Rhizobium strain E20-8, but under osmotic stress (PEG) GO decreased bacterial growth even at lower concentrations. GO caused oxidative stress, with antioxidant mechanisms being induced to restrain damage, effectively at lower concentrations, but less effective at higher concentrations, and oxidative damage overcame. Under osmotic stress, alginate and glycine betaine osmoregulated the bacteria. Simultaneous exposure to PEG and GO induced oxidative damage. Plant growth promotion traits (indole acetic acid and siderophores production) were increased by osmotic stress and GO did not disturb these abilities. In the context of climate change, our findings might be relevant as they can form the premises for the implementation of crop production methodologies adapted to the new prevailing conditions, which include the presence of nanoparticles in the soil and more frequent and severe drought.