Given that the effects of ultrafine fractions (<0.1 ?m) on ischemic heart diseases (IHD) and other cardiovascular diseases are gaining attention, this study is aimed to explore the influence of silica nanoparticles (SiNPs)-induced autophagy on endothelial cell homeostasis and angiogenesis.
Quantum dots (QDs) have been used as novel fluorescent nanoprobes for various bioapplications. The degradation of QDs, and consequent release of free cadmium ions, have been suggested to be the causes of their overall toxicity. However, in contrast to sufficient investigations regarding the biological fate of QDs, a paucity of studies have reported their chemical fate in vivo. Therefore, the overall aim of our study was to understand the chemical fate of QDs in vivo and explore analytical techniques or methods that could be used to define the chemical fate of QDs in vivo.
Silica nanoparticles (SNPs) are one of the most important nanomaterials, and have been widely used in a variety of fields. Therefore, their effects on human health and the environment have been addressed in a number of studies. In this work, the effects of amorphous SNPs were investigated with regard to multinucleation in L-02 human hepatic cells. Our results show that L-02 cells had an abnormally high incidence of multinucleation upon exposure to silica, that increased in a dose-dependent manner. Propidium iodide staining showed that multinucleated cells were arrested in G2/M phase of the cell cycle. Increased multinucleation in L-02 cells was associated with increased generation of cellular reactive oxygen species and mitochondrial damage on flow cytometry and confocal microscopy, which might have led to failure of cytokinesis in these cells. Further, SNPs inhibited cell growth and induced apoptosis in exposed cells. Taken together, our findings demonstrate that multinucleation in L-02 human hepatic cells might be a failure to undergo cytokinesis or cell fusion in response to SNPs, and the increase in cellular reactive oxygen species could be responsible for the apoptosis seen in both mononuclear cells and multinucleated cells.
Silica nanoparticles (SiNPs) have been widely used in biomedical and biotechnological applications. Environmental exposure to nanomaterials is inevitable as they become part of our daily life. Therefore, it is necessary to investigate the possible toxic effects of SiNPs exposure. In this study, zebrafish embryos were treated with SiNPs (25, 50, 100, 200 µg/mL) during 4-96 hours post fertilization (hpf). Mortality, hatching rate, malformation and whole-embryo cellular death were detected. We also measured the larval behavior to analyze whether SiNPs had adverse effects on larvae locomotor activity. The results showed that as the exposure dosages increasing, the hatching rate of zebrafish embryos was decreased while the mortality and cell death were increased. Exposure to SiNPs caused embryonic malformations, including pericardial edema, yolk sac edema, tail and head malformation. The larval behavior testing showed that the total swimming distance was decreased in a dose-dependent manner. The lower dose (25 and 50 µg/mL SiNPs) produced substantial hyperactivity while the higher doses (100 and 200 µg/mL SiNPs) elicited remarkably hypoactivity in dark periods. In summary, our data indicated that SiNPs caused embryonic developmental toxicity, resulted in persistent effects on larval behavior.
Silica nanoparticles have become promising carriers for drug delivery or gene therapy. Endothelial cells could be directly exposed to silica nanoparticles by intravenous administration. However, the underlying toxic effect mechanisms of silica nanoparticles on endothelial cells are still poorly understood. In order to clarify the cytotoxicity of endothelial cells induced by silica nanoparticles and its mechanisms, cellular morphology, cell viability and lactate dehydrogenase (LDH) release were observed in human umbilical vein endothelial cells (HUVECs) as assessing cytotoxicity, resulted in a dose- and time- dependent manner. Silica nanoparticles-induced reactive oxygen species (ROS) generation caused oxidative damage followed by the production of malondialdehyde (MDA) as well as the inhibition of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Both necrosis and apoptosis were increased significantly after 24 h exposure. The mitochondrial membrane potential (MMP) decreased obviously in a dose-dependent manner. The degree of DNA damage including the percentage of tail DNA, tail length and Olive tail moment (OTM) were markedly aggravated. Silica nanoparticles also induced G2/M arrest through the upregulation of Chk1 and the downregulation of Cdc25C, cyclin B1/Cdc2. In summary, our data indicated that the toxic effect mechanisms of silica nanoparticles on endothelial cells was through DNA damage response (DDR) via Chk1-dependent G2/M checkpoint signaling pathway, suggesting that exposure to silica nanoparticles could be a potential hazards for the development of cardiovascular diseases.
Polybrominated diphenyl ethers (PBDEs) and dechlorane plus (DP) are two kinds of widely used organic flame retardants, and PBDE and DP residues have been found in both environment and biota. A method for the determination of 8 PBDEs and 2 DPs in fish and fish oil supplements was developed using auto gel permeation chromatography (GPC) coupled with gas chromatography-negative chemical ionization/mass spectrometry (GC-NCI/MS) in the selected ion-monitoring (SIM) mode on a 15 m capillary column. The sample added with BDE-77 and 13C12-BDE-209 as the internal standards was extracted using a Soxhlet extractor, and further purified by auto GPC and a multilayer silica gel column. The sample preparation procedure was optimized, and the characteristic ions and fragmentations of the analytes in NCI/MS were studied. The limits of detection (LODs, S/N = 3) ranged from 2.2 to 39.8 ng/kg. The average recoveries were between 71.1% and 121.4% at two spiked levels of 2 and 20 ng/g for both BDE-209 and DP and 0.2 and 2 ng/g for others with the relative standard deviations between 2.96% and 13.31%. The developed method has been successfully applied in the determination of PBDEs and DPs in several fish and fish oil supplements samples. The total PBDEs found ranged from 2.18 to 15.93 ng/g, and DP was not found. This method was validated to be accurate and sensitive for the trace analysis of PBDEs and DPs in the samples with fat.
A novel block ionomer complex micelles as drug carrier is developed utilizing self-assemble of poly(ethylene glycol)-block-poly(acrylic acid) (PEG-b-PAA) and cadmium chloride. This micelles are characterized to be have good bio-compatibility, hydrophilicity, passive targeting and sustained slow release property which shows great potential for liver cancer therapy. Block ionomer complex micelles based on PEG-b-PAA and cadmium chloride can self-assemble in distilled water, and Cd(²+) agent is entrapped into the core stabilized by PEG shells. Results showed the block ionomer complex micelles to be spherically shaped. Cadmium was incorporated easily into the ionic core with remarkably high efficiency (34.25% weight (wt)/wt). The cadmium-loaded polymeric micelles exhibited sustained and slow release behavior of cadmium and a potent cytotoxicity against SMMC-7721 in vitro. This novel block ionomer complex micelles with cores of metal antitumor drug indicates to be potential carriers for effective drug delivery.
The purpose of this study is to compare the potential cytotoxicity induced by amorphous silica particles with different sizes. The effects of one fine particle (498 nm) and three nanoparticles (68, 43, and 19 nm) on cultured human hepatoma (HepG2) cells were investigated by detecting morphological changes, cell viability, cytomembrane integrity, DNA damage, cell cycle distribution, and apoptosis after the cells were treated with 100 ?g/mL of four silica particles for 24h. The results indicated that in HepG2 cells, the cytotoxicity generated by silica particles strongly depended on the particle size, and smaller silica particle possessed higher toxic effect. In order to further elucidate the possible mechanisms of cell injuries, intracellular reactive oxygen species (ROS) was measured. Increased ROS level was also observed in a size dependent way. However, the result showed the fine particle did not promote intracellular ROS level significantly, while cell injuries were detected in this treated group. Thus, our data demonstrated that exposure to different sizes of silica particles resulted in a size dependent cytotoxicity in cultured HepG2 cells, and ROS generation should be one possible damage pathway but might not be completely responsible for the toxic effect produced by silica particles.
Amorphous silica nanoparticles are widely applied in many fields. But the adverse effects of silica nanoparticle exposure were unclear. The present study investigated the cytotoxicity and mitochondrial damage of silica nanoparticles exposure in hepatocellular carcinoma cell line (HepG2). The cells were treated with 43 nm non-modified amorphous silica nanoparticles which dispersed in serum-free DMEM at concentrations of 0, 25, 50, 100 and 200 ?g/mL for 3 and 24 h. The results showed that the silica nanoparticles could lead to increasing cellular reactive oxygen species (ROS) production for 3 and 24 h exposure. Moreover, the oxidative stress induced by the particles could play an important role of the mitochondrial membrane damage and the cell apoptosis. It indicated that apoptosis through mitochondrial pathway mediated by oxidative stress was a potential mechanism of cytotoxicity induced by silica nanoparticles. The particles could enter the cells through different pathways and dispersed in cytoplasm and deposited inside mitochondria. Mitochondria were the major organelles for the cytotoxicity of silica nanoparticles exposure. Mitochondrial damage was related to the oxidative stress and the direct injurious effect of nanoparticles. It can be considered as the potential mechanism for the cytotoxic effects of amorphous silica nanoparticles.
Manganese (Mn) toxicity is most often found in mining and welding industry workers. Accumulation of manganese in the brain can result in a syndrome similar to that of Parkinsons disease. Observations on former Mn-alloy workers suggested that residual effects could last for years after exposure. The objective of this study was to assess effects of Mn in the liver of rats following subacute or subchronic exposure and after recovery. Male Sprague-Dawley rats were exposed to manganese chloride (MnCl(2)) for 30 days, 90 days, or for 90 days followed by a 30-day post-exposure recovery period. Results showed that MnCl(2) exposure resulted in liver injury in rats and the extent of injury correlated positively with exposure time. The effect in mitochondria was stronger than in the membrane or nucleus. Most of the changes in these biomarkers recovered when manganese exposure ceased.
Toxicity due to overexposure to manganese (Mn) is becoming increasingly prevalent. Mn-induced neurodegenerative toxicity has been demonstrated, but little is known concerning the adverse effects of the element on the liver. Under physiological conditions, manganese primarily exists as divalent manganese (Mn(2+)) and trivalent manganese (Mn(3+)). The present study was designed to evaluate and compare the effects of Mn(2+) and Mn(3+) on oxidative hepatic damage, membrane fluidity and histopathological changes in rats. Rats exposed to Mn(2+) or Mn(3+) (2.0mg Mn/kg body weight) showed significant inhibition of superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, as well as decreased levels of glutathione (GSH) and increased levels of malondialdehyde (MDA) in liver tissues. We also showed a significant inhibition of SOD activity and increased MDA levels in hepatocyte nuclei. We also observed reduced Na(+),K(+)-ATPase activity, increased MDA levels and decreased plasma membrane fluidity, which was accompanied by an increase of fluorescence anisotropy (r) values, in hepatic plasma membranes. In addition, Mn(2+) and Mn(3+) both caused histopathological changes, such as mononuclear cell infiltration, congestion, enlargement of the veins and sinusoids, hepatocellular damage, necrotic changes, mitochondrial hyperplasia, swelling and vacuolization, as determined by light and electron microscopy. Taken together, these data suggest that both Mn(2+) and Mn(3+) inhibit the normal physiological functioning of the liver. Under the experimental conditions used, the adverse effects of Mn(2+) were more severe than those of Mn(3+).
The aim of this study was to investigate the contents of lanthanum (La), cerium (Ce), and neodymium (Nd) that accumulate in nuclei and mitochondria isolated from the liver and their corresponding potential oxidative damage effects on nuclei and mitochondria. Five-week-old male imprinting control region (ICR) mice were exposed to chlorides of La, Ce, or Nd by oral gavage with one of three doses: 10, 20, or 40 mg/kgBW/day for 6 weeks. The concentrations of administered elements in hepatocyte nuclei and mitochondria were determined with inductively coupled plasma-mass (ICP-MS) spectrometry. The accumulation of La, Ce, and Nd in hepatocyte nuclei and mitochondria gradually increased in a dose-dependent manner with exposure to the elements, although the concentrations of La, Ce, and Nd in hepatocyte mitochondria were lower than those in their counterpart nuclei. In hepatocyte nuclei, superoxide dismutase (SOD) and catalase (CAT) activities decreased, whereas glutathione peroxidase (GPx) activity, glutathione (GSH) and malondialdehyde (MDA) levels increased. In hepatocyte mitochondria, SOD, CAT, and GPx activities and GSH levels were significantly decreased, and MDA levels were significantly increased. These results suggest that La, Ce, and Nd presumably enter hepatocytes and mainly accumulate in the nuclei and induce oxidative damage in hepatic nuclei and mitochondria.
Nanotechnology has been increasingly applied to various fields, such as biology, chemistry, physics, medicine and engineering. However, a major concern that has been the topic in nanoscience is whether exposure of humans to engineered nanoparticles might cause toxic effects. In the present in vitro study, the influence of silica nanoparticles on fibronectin-mediated cellular response was assessed in normal human keratinocytes. Our results demonstrated that silica nanoparticles but not silica microparticles significantly suppressed cell adhesion and migration to fibronectin. This phenomenon was not observed in cell response to Poly-L-Lysine, which mediates cell adhesion and migration in a way different from that of fibronectin. Moreover, it seemed that this suppression was not due to cytotoxic effects induced by silica nanoparticles. Subsequently, we also showed that silica nanoparticles impaired the fibronectin-induced activation of FAK and its downstream PI3K, AKT and Src. Taken together, our data suggests that silica nanoparticles may negatively modulate cell response to fibronectin.
To investigate the effects of CdTe QDs (cadmium telluride quantum dots) on oxidative stress and DNA damage of liver cells in mice.
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