Toxicity Of ZnO Nanoparticles Research Articles

Time-Dependent Toxicity Responses in Daphnia magna Exposed to CuO and ZnO Nanoparticles.

Aggregation and dissolution of CuO and ZnO nanoparticles (NPs) increased with increasing exposure time (24, 48, and 72h). Acute toxicity of CuO NPs to Daphnia magna also increased significantly with increasing exposure time (p < 0.05), whereas exposure time did not significantly affect acute toxicity of ZnO NPs. The dissolved Cu concentration of CuO NPs was much lower than the median effective concentration (EC50) value (44μgL-1 at 72h), implying that the increase in acute toxicity was caused by particles rather than by dissolved ions. However, the dissolved Zn concentration of ZnO NPs was higher than the EC50 value (600μgL-1 at 72h), suggesting this acute toxicity may be caused by dissolved ions. Moreover, CuO NPs induced greater lipid peroxidation than Cu ions did at an exposure time of 72h, whereas converse results were observed for ZnO NPs.

The effects of endoplasmic reticulum stress inducer thapsigargin on the toxicity of ZnO or TiO2 nanoparticles to human endothelial cells

It was recently shown that ZnO nanoparticles (NPs) could induce endoplasmic reticulum (ER) stress in human umbilical vein endothelial cells (HUVECs). If ER stress is associated the toxicity of ZnO NPs, the presence of ER stress inducer thapsigargin (TG) should alter the response of HUVECs to ZnO NP exposure. In this study, we addressed this issue by assessing cytotoxicity, oxidative stress and inflammatory responses in ZnO NP exposed HUVECs with or without the presence of TG. Moreover, TiO2 NPs were used to compare the effects. Exposure to 32 μg/mL ZnO NPs (p < 0.05), but not TiO2 NPs (p > 0.05), significantly induced cytotoxicity as assessed by WST-1 and neutral red uptake assay, as well as intracellular ROS. ZnO NPs dose-dependently increased the accumulation of intracellular Zn ions, and ZnSO4 induced similar cytotoxic effects as ZnO NPs, which indicated a role of Zn ions. The release of inflammatory proteins tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) or the adhesion of THP-1 monocytes to HUVECs was not significantly affected by ZnO or TiO2 NP exposure (p > 0.05). The presence of 250 nM TG significantly induced cytotoxicity, release of IL-6 and THP-1 monocyte adhesion (p < 0.01), but did not significantly affect intracellular ROS or release of TNFα (p > 0.05). ANOVA analysis indicated no interaction between exposure to ZnO NPs and the presence of TG on almost all the endpoints (p > 0.05) except neutral red uptake assay (p < 0.01). We concluded ER stress is probably not associated with ZnO NP exposure induced oxidative stress and inflammatory responses in HUVECs.

Low toxicity and accumulation of zinc oxide nanoparticles in mice after 270-day consecutive dietary supplementation.

The toxicity and accumulation of zinc oxide nanoparticles (ZnO-NPs), ZnO microparticles (ZnO-MPs) and Zn ions were evaluated after long-term feeding with zinc-replenished food (1600 mg zinc equivalent per kg food) for 270 consecutive days. It was difficult for ZnO-NPs, ZnO-MPs and Zn ions were difficult to pass through the intestine barrier, and most of them were excreted mainly through feces. The distribution results showed that there was no noticeable difference among the distribution profiles of ZnO-NPs, ZnO-MPs and Zn ions in mice. Zn accumulated only in the digestive tract organs after the exposure to all three samples. However, the biomedical parameters and pathological investigations showed liver lesions induced by ZnO-MPs, but fewer by ZnO-NPs or Zn ions. The reason for the remarkably low in vivo toxicity of ZnO-NPs is discussed. Our findings suggest that ZnO-NPs are relatively biocompatible as the nutritional additive at the commonly used dose.

Investigating the Toxicity of Cu, CuO and ZnO Nanoparticles on Earthworms in Urban Soils

Even though some studies have shown that copper (Cu), copper oxide (CuO) and zinc oxide (ZnO) nanoparticles (NPs) are toxic to a number of organisms, fewer studies have investigated toxicity of these NPs in actual soils. This study investigated the effect of Cu, CuO and ZnO NPs in both urban and artificial soils. The aim was to examine the differences on these NPs’ ability to cause oxidative stress to organisms in urban and artificial soils. Earthworms, Eisenia fetida, (2 months old) were exposed to varying concentrations of NPs and bulk materials (used for comparison purposes) of Cu, CuO and ZnO ranging from 100-500 mg/kg, 100-4000 mg/kg and 100-4000 mg/kg, respectively, for 14 days, for each soil type. Superoxide dismutase (SOD), reduced glutathione (GSH) and hydrogen peroxide (H2O2) were measured at the end of exposure period. The accumulation of Cu and Zn in the earthworm tissues was measured using AAS. In urban soils, SOD, GSH and H2O2 all showed an initial increase as the concentration of NPs increased and but decreased at higher concentrations. Similar results for bulk materials were observed, though with less intensity. Cu and Zn accumulation in earthworm tissues increased as a function of NPs/bulk materials concentrations in both soils. Interestingly however, SOD, GSH and H2O2 from artificial soils for both NPs and bulk materials did not show significant differences from the controls, except at higher NPs/bulk materials concentrations.

Strategy of metal iron doping and green-mediated ZnO nanoparticles: dissolubility, antibacterial and cytotoxic traits.

Undoped and Fe-doped ZnO nanoparticles (NPs) were synthesized using Amaranthus spinosus leaf extract as a reducing agent. The physicochemical traits, dissolution, cytotoxicity, as well as the antioxidant, photocatalytic and antibacterial activities of synthesized NPs were investigated. The results revealed that ZnO NPs were rod shaped with hexagonal phase structure, and their crystal size, dissolubility and aggregation decreased with Fe doping of NPs. Cytotoxicity of the NPs was studied against MCF-7 cells by MTT assay. IC50 values for undoped and 1 wt% Fe-doped ZnO NPs were found to be 400 and 600 μg mL-1, respectively. Cell viability with Fe-doped ZnO NPs was higher than with undoped ZnO. Among the synthesized NPs, A. spinosus-mediated 1 wt% Fe-doped ZnO shows a better decolourization efficiency of 97% for indigo carmine dye under solar irradiance. The antibacterial activity of NPs was tested against Gram-negative Escherichia coli and Gram-positive Bacillus safensis using disc diffusion, minimum inhibitory concentration and growth curve method. The bactericidal activity of Fe-doped ZnO NPs was more prominent with E. coli than B. safensis bacteria and when compared to undoped ZnO.

Evaluating the effect of zinc oxide nanoparticles on the physiological responses of nine non-photoperiod sensitive rice cultivars

The effects of nanopaticles on plant growth and metabolites have been reported in previous studies, but knowledge of the potential impacts of physiological responses is still unclear. Therefore, this study focused on the effect of exposure of zinc oxide (ZnO) nanoparticles on photosynthetic pigment contents (chlorophyll A, chlorophyll B and carotenoids) and the antioxidant enzyme activities (catalase and peroxidase) in nine non-photoperiod sensitive rice cultivars consisting of RD41, RD49, Chai Nat 1, Suphan Buri 1, Suphan Buri 2, Suphan Buri 3, Pathum Thani 1, Pathum Thani 80 and Phitsanulok 2. Rice plants were treated with 200 mg L-1 ZnO nanoparticles for every 15 days-interval. Rice plants were collected at 37, 44 and 51 days after planting for the evaluation of ZnO nanoparticles toxicity. The results showed that nine non-photoperiod sensitive rice cultivars treated with ZnO nanoparticle, as determined by the reduction of photosynthetic pigment contents. The activities of antioxidant enzymes protected plant cell when exposed to the toxicity of ZnO nanoparticles. This study showed that the supplementation of ZnO nanoparticles was no significant difference in photosynthetic pigment contents of rice cultivars. The results indicated that the accumulation of antioxidant enzyme activities could be protecting damage of the photosynthetic pigments in plant cells.

Comparative study on toxicity of ZnO and TiO2 nanoparticles on Artemia salina: effect of pre-UV-A and visible light irradiation.

This study evaluated the toxicity potential of ZnO and TiO2 nanoparticles under pre-UV-A irradiation and visible light condition on Artemia salina. The nanoparticle suspension was prepared in seawater medium and exposed under pre-UV-A (0.23mW/cm2) and visible light (0.18mW/cm2) conditions. The aggregation profiles of both nanoparticles (NPs) and dissolution of ZnO NPs under both irradiation conditions at various kinetic intervals (1, 24, 48h) were studied. The 48-h LC50 values were found to be 27.62 and 71.63mg/L for ZnO NPs and 117 and 120.9mg/L for TiO2 NPs under pre-UV-A and visible light conditions. ZnO NPs were found to be more toxic to A. salina as compared to TiO2 NPs. The enhanced toxicity was observed under pre-UV-A-irradiated ZnO NPs, signifying its phototoxicity. Accumulation of ZnO and TiO2 NPs into A. salina depends on the concentration of particles and type irradiations. Elimination of accumulated nanoparticles was also evident under both irradiation conditions. Other than ZnO NPs, the dissolved Zn2+ also had a significant effect on toxicity and accumulation in A. salina. Increased catalase (CAT) activity in A. salina indicates the generation of oxidative stress due to NP interaction. Thus, this study provides an understanding of the toxicity of photoreactive ZnO and TiO2 NPs as related to the effects of pre-UV-A and visible light irradiation.

Elevated CO2 levels increase the toxicity of ZnO nanoparticles to goldfish (Carassius auratus) in a water-sediment ecosystem

Concerns about the environmental safety of metal-based nanoparticles (MNPs) in aquatic ecosystems are increasing. Simultaneously, elevated atmospheric CO2 levels are a serious problem worldwide, making it possible for the combined exposure of MNPs and elevated CO2 to the ecosystem. Here we studied the toxicity of nZnO to goldfish in a water-sediment ecosystem using open-top chambers flushed with ambient (400±10μL/L) or elevated (600±10μL/L) CO2 for 30days. We measured the content of Zn in suspension and fish, and analyzed physiological and biochemical changes in fish tissues. Results showed that elevated CO2 increased the Zn content in suspension by reducing the pH value of water and consequently enhanced the bioavailability and toxicity of nZnO. Elevated CO2 led to higher accumulation of Zn in fish tissues (increased by 43.3%, 86.4% and 22.5% in liver, brain and muscle, respectively) when compared to ambient. Elevated CO2 also intensified the oxidative damage to fish induced by nZnO, resulting in higher ROS intensity, greater contents of MDA and MT and lower GSH content in liver and brain. Our results suggest that more studies in natural ecosystems are needed to better understand the fate and toxicity of nanoparticles in future CO2 levels.

Sodium alginate and gum acacia hydrogels of ZnO nanoparticles show wound healing effect on fibroblast cells

An ideal biomaterial for wound dressing applications should possess antibacterial and anti-inflammatory properties without any toxicity to the host cells while providing the maximum healing activity. Zinc oxide nanoparticles (ZnONPs) possess antimicrobial activity and enhance wound healing, but the questions regarding their safety arise before application to the biological systems. We synthesized ZnONPs-loaded-sodium alginate-gum acacia hydrogels (SAGA-ZnONPs) by cross linking hydroxyl groups of the polymers sodium alginate and gum acacia with the aldehyde group of gluteradehyde. Here, we report the wound healing properties of sodium alginate/gum acacia/ZnONPs, circumventing the toxicity of ZnONPs simultaneously. We demonstrated the concentration-dependent zones of inhibition in treated cultures of Pseudomonas aerigunosa and Bacillus cereus and biocompatability on peripheral blood mononuclear/fibroblast cells. SAGA-ZnONPs hydrogels showed a healing effect at a low concentration of ZnONPs using sheep fibroblast cells. Our findings suggest that high concentrations of ZnONPs were toxic to cells but SAGA-ZnONPs hydrogels significantly reduced the toxicity and preserved the beneficial antibacterial and healing effect.

Chronic ZnO-NPs exposure at environmentally relevant concentrations results in metabolic and locomotive toxicities in Caenorhabditis elegans

ZnO nanoparticles (ZnO-NPs) are emerging contaminants that raise the concerns of potential risk in the aquatic environment. It has been estimated that the environmental ZnO-NPs concentration is 76 μg/l in the aquatic environment. Our aim was to determine the aquatic toxicity of ZnO-NPs with chronic exposure at environmentally relevant concentrations using the nematode Caenorhabditis elegans. Two simulated environmentally relevant mediums—moderately hard reconstituted water (EPA water) and simulated soil pore water (SSPW)—were used to represent surface water and pore water in sediment, respectively. The results showed that the ZnO-NPs in EPA water has a much smaller hydrodynamic diameter than that in SSPW. Although the ionic release of Zn ions increased time-dependently in both mediums, the Zn ions concentrations in EPA water increased two-fold more than that in SSPW at 48 h and 72 h. The ZnO-NPs did not induce growth defects or decrease head thrashes in C. elegans in either media. However, chronic exposure to ZnO-NPs caused a significant reduction in C. elegans body bends in EPA water even with a relatively low concentration (0.05 μg/l); similar results were not observed in SSPW. Moreover, at the same concentrations (50 and 500 μg/l), body bends in C. elegans were reduced more severely in ZnO-NPs than in ZnCl2 in EPA water. The ATP levels were consistently and significantly decreased, and ROS was induced after ZnO-NPs exposure (50 and 500 μg/l) in EPA water. Our results provide evidences that chronic exposure to ZnO-NPs under environmentally relevant concentrations causes metabolic and locomotive toxicities implicating the potential ecotoxicity of ZnO-NPs at low concentrations in aquatic environments.

Chronic toxicity effects of ZnSO4 and ZnO nanoparticles in Daphnia magna

The chronic toxicity of ZnSO4 and ZnO nanoparticles has been studied in Daphnia magna also considering the life cycle parameters beyond the standard 21-day exposure time. Specimens have been individually followed until the natural end of their life, and some of them sampled for microscopic analyses at 48h, 9 and 21 days. Despite the low level of exposure (0.3mg Zn/L), ultrastructural analyses of the midgut epithelial cells revealed efficient internalization of nanoparticles between 48h and 9d, and translocation to other tissues as well. At 21d, the most affected fields have been recorded for both compounds; in particular samples exposed to ZnO nanoparticles showed swelling of mitochondria, while those exposed to ZnSO4 had a great number of autophagy vacuoles. The life cycle parameters resulted altered as well, with a significant inhibition of reproduction in both groups, when compared to controls. After the 21-day exposure, some interesting results were obtained: animals, previously exposed to nanoZnO at low concentrations, showed a complete recovery of the full reproduction potential, while those previously exposed to ZnSO4 presented a dose-dependent and compound-specific reduction in lifespan. Based on the results from the present research and the effects of the same chemicals at higher doses, it can be concluded that the soluble form plays a key role in ZnO nanoparticle cytotoxicity, and that the nanoparticulate form is able to locally increase the amount of Zn inside the cell, even within the ovary. It's worth noting that ZnO nanoparticles have been internalized despite the very low concentration used: this raises concern about the possible environmental implications which may derive from their use, and which in turn must be carefully considered.

Combined effects of low levels of palmitate on toxicity of ZnO nanoparticles to THP-1 macrophages.

We have recently proposed that the interaction between food components and nanoparticles (NPs) should be considered when evaluating the toxicity of NPs. In the present study, we used THP-1 differentiated macrophages as a model for immune cells and investigated the combined toxicity of low levels of palmitate (PA; 10 or 50μM) and ZnO NPs. The results showed that PA especially at 50μM changed the size, Zeta potential and UV-vis spectra of ZnO NPs, indicating a possible coating effect. Up to 32μg/mL ZnO NPs did not significantly affect mitochondrial activity, intracellular reactive oxygen species (ROS) or release of interleukin 6 (IL-6), but significantly impaired lysosomal function as assessed by neutral red uptake assay and acridine orange staining. The presence of 50μM PA, but not 10μM PA, further promoted the toxic effects of ZnO NPs to lysosomes but did not significantly affect other endpoints. In addition, ZnO NPs dose-dependently increased intracellular Zn ions in THP-1 macrophages, which was not significantly affected by PA. Taken together, the results of the present study showed a combined toxicity of low levels of PA and ZnO NPs especially to lysosomes in THP-1 macrophages.

Toxicity of ZnO and TiO2 to Escherichia coli cells.

We performed a comprehensive investigation of the toxicity of ZnO and TiO2 nanoparticles using Escherichia coli as a model organism. Both materials are wide band gap n-type semiconductors and they can interact with lipopolysaccharide molecules present in the outer membrane of E. coli, as well as produce reactive oxygen species (ROS) under UV illumination. Despite the similarities in their properties, the response of the bacteria to the two nanomaterials was fundamentally different. When the ROS generation is observed, the toxicity of nanomaterial is commonly attributed to oxidative stress and cell membrane damage caused by lipid peroxidation. However, we found that significant toxicity does not necessarily correlate with up-regulation of ROS-related proteins. TiO2 exhibited significant antibacterial activity, but the protein expression profile of bacteria exposed to TiO2 was different compared to H2O2 and the ROS-related proteins were not strongly expressed. On the other hand, ZnO exhibited lower antibacterial activity compared to TiO2, and the bacterial response involved up-regulating ROS-related proteins similar to the bacterial response to the exposure to H2O2. Reasons for the observed differences in toxicity and bacterial response to the two metal oxides are discussed.

Zinc Oxide Nanoparticle Induces Microglial Death by NADPH-Oxidase-Independent Reactive Oxygen Species as well as Energy Depletion.

Zinc oxide nanoparticle (ZnO-NP) is one of the most widely used engineered nanoparticles. Upon exposure, nanoparticle can eventually reach the brain through various routes, interact with different brain cells, and alter their activity. Microglia is the fastest glial cell to respond to any toxic insult. Nanoparticle exposure can activate microglia and induce neuroinflammation. Simultaneous to activation, microglial death can exacerbate the scenario. Therefore, we focused on studying the effect of ZnO-NP on microglia and finding out the pathway involved in the microglial death. The present study showed that the 24h inhibitory concentration 50 (IC50) of ZnO-NP for microglia is 6.6μg/ml. Early events following ZnO-NP exposure involved increase in intracellular calcium level as well as reactive oxygen species (ROS). Neither of NADPH oxidase inhibitors, apocynin,(APO) and diphenyleneiodonium chloride (DPIC) were able to reduce the ROS level and rescue microglia from ZnO-NP toxicity. In contrary, N-acetyl cysteine (NAC) showed opposite effect. Exogenous supplementation of superoxide dismutase (SOD) reduced ROS significantly even beyond control level but partially rescued microglial viability. Interestingly, pyruvate supplementation rescued microglia near to control level. Following 10h of ZnO-NP exposure, intracellular ATP level was measured to be almost 50% to the control. ZnO-NP-induced ROS as well as ATP depletion both disturbed mitochondrial membrane potential and subsequently triggered the apoptotic pathway. The level of apoptosis-inducing proteins was measured by western blot analysis and found to be upregulated. Taken together, we have deciphered that ZnO-NP induced microglial apoptosis by NADPH oxidase-independent ROS as well as ATP depletion.

Cytotoxic effects of ZnO nanoparticles on mouse testicular cells.

BackgroundNanoscience and nanotechnology are developing rapidly, and the applications of nanoparticles (NPs) have been found in several fields. At present, NPs are widely used in traditional consumer and industrial products, however, the properties and safety of NPs are still unclear and there are concerns about their potential environmental and health effects. The aim of the present study was to investigate the potential toxicity of ZnO NPs on testicular cells using both in vitro and in vivo systems in a mouse experimental model.MethodsZnO NPs with a crystalline size of 70 nm were characterized with various analytical techniques, including ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, and atomic force microscopy. The cytotoxicity of the ZnO NPs was examined in vitro on Leydig cell and Sertoli cell lines, and in vivo on the testes of CD1 mice injected with single doses of ZnO NPs.ResultsZnO NPs were internalized by Leydig cells and Sertoli cells, and this resulted in cytotoxicity in a time- and dose-dependent manner through the induction of apoptosis. Apoptosis likely occurred as a consequence of DNA damage (detected as γ-H2AX and RAD51 foci) caused by increase in reactive oxygen species associated with loss of mitochondrial membrane potential. In addition, injection of ZnO NPs in male mice caused structural alterations in the seminiferous epithelium and sperm abnormalities.ConclusionThese results demonstrate that ZnO NPs have the potential to induce apoptosis in testicular cells likely through DNA damage caused by reactive oxygen species, with possible adverse consequences for spermatogenesis and therefore, male fertility. This suggests that evaluating the potential impacts of engineered NPs is essential prior to their mass production, to address both the environmental and human health concerns and also to develop sustainable and safer nanomaterials.

Reducing ZnO nanoparticles toxicity through silica coating.

ZnO NPs have good antimicrobial activity that can be utilized as agents to prevent harmful microorganism growth in food. However, the use of ZnO NPs as food additive is limited by the perceived high toxicity of ZnO NPs in many earlier toxicity studies. In this study, surface modification by silica coating was used to reduce the toxicity of ZnO NPs by significantly reducing the dissolution of the core ZnO NPs. To more accurately recapitulate the scenario of ingested ZnO NPs, we tested our as synthesized ZnO NPs in ingestion fluids (synthetic saliva and synthetic gastric juice) to determine the possible forms of ZnO NPs in digestive system before exposing the products to colorectal cell lines. The results showed that silica coating is highly effective in reducing toxicity of ZnO NPs through prevention of the dissociation of ZnO NPs to zinc ions in both neutral and acidic condition. The silica coating however did not alter the desired antimicrobial activity of ZnO NPs to E. coli and S. aureus. Thus, silica coating offered a potential solution to improve the biocompatibility of ZnO NPs for applications such as antimicrobial agent in foods or food related products like food packaging. Nevertheless, caution remains that high concentration of silica coated ZnO NPs can still induce undesirable cytotoxicity to mammalian gut cells. This study indicated that upstream safer-by-design philosophy in nanotechnology can be very helpful in a product development.

Developmental toxicity of intravenously injected zinc oxide nanoparticles in rats.

Recent toxicity studies of zinc oxide nanoparticles by oral administration showed relatively low toxicity, which may be resulted from low bioavailability. So, the intrinsic toxicity of zinc oxide nanoparticles needs to be evaluated in the target organs by intravenous injection for full systemic concentration of the administered dosage. Although the exposure chance of injection route is low compared to oral and/or inhalation route, it is important to see the toxicity with different exposure routes to get better risk management tool. In this study, the effects of zinc oxide nanoparticles on dams and fetuses were investigated in rats after intravenous injection (5, 10, and 20mg/kg) from gestation day 6 to 20. Two of 20 dams in the 20mg/kg treatment group died during the treatment period. Hematological examination and serum biochemistry showed dose-dependent toxicity in treated dams. Histopathological analysis of treated dams revealed multifocal mixed cell infiltration and thrombosis in lung, tubular dilation in kidneys, and extramedullary hemopoiesis in liver. Total dead fetuses (post-implantation loss) were increased and the body weight of fetus was decreased in the 20mg/kg treatment group. Statistical differences in corpora lutea, resorption, placental weight, morphological alterations including external, visceral and skeletal malformations were not observed in treated groups. Based on the data, lowest observed adverse effect level of injection route was suggested to be 5mg/kg in dams and no observed adverse effect level was suggested to be 10mg/kg in fetal developmental toxicity.

Engineered Nanoparticles as Potential Food Contaminants and Their Toxicity to Caco-2 Cells.

Engineered nanoparticles (ENPs), such as metallic or metallic oxide nanoparticles (NPs), have gained much attention in recent years. Increasing use of ENPs in various areas may lead to the release of ENPs into the environment and cause the contamination of agricultural and food products by ENPs. In this study, we selected two important ENPs (zinc oxide [ZnO] and silver [Ag] NPs) as potential food contaminants and investigated their toxicity via an in vitro model using Caco-2 cells. The physical properties of ENPs and their effects on Caco-2 cells were characterized by electron microscopy and energy dispersive X-ray spectroscopic (EDS) techniques. Results demonstrate that a significant inhibition of cell viability was observed after a 24-h of exposure of Caco-2 cells to 3-, 6-, and 12-mM ZnO NPs or 0.5-, 1.5-, and 3-mM Ag NPs. The noticeable changes of cells include the alteration in cell shape, abnormal nuclear structure, membrane blebbing, and cytoplasmic deterioration. The toxicity of ZnO NPs, but not that of Ag NPs after exposure to simulated gastric fluid, significantly decreased. Scanning transmission electron microscopy shows that ZnO and Ag NPs penetrated the membrane of Caco-2 cells. EDS results also confirm the presence of NPs in the cytoplasm of the cells. This study demonstrates that ZnO and Ag NPs have cytotoxic effects and can inhibit the growth of Caco-2 cells.

Synergistic toxicity of zno nanoparticles and dimethoate in mice: Enhancing their biodistribution by synergistic binding of serum albumin and dimethoate to zno nanoparticles.

The extensive applications of ZnO nanoparticles (nano ZnO) and dimethoate (DM) have increased the risk of humans' co-exposure to nano ZnO and DM. Here, we report the synergistic effect of nano ZnO and DM on their biodistribution and subacute toxicity in mice. Nano ZnO and DM had a synergistic toxicity in mice. In contrast, bulk ZnO and DM did not cause an obvious synergistic toxicity in mice. Although nano ZnO was low toxic to mice, coexposure to nano ZnO and DM significantly enhanced DM-induced oxidative damage in the liver. Coadministration of nano ZnO with DM significantly increased Zn accumulation by 30.9±1.9% and DM accumulation by 45.6±2.2% in the liver, respectively. The increased accumulations of DM and Zn in the liver reduced its cholinesterase activity from 5.65±0.32 to 4.37±0.49U/mg protein and induced hepatic oxidative stress. Nano ZnO had 3-fold or 2.4-fold higher binding capability for serum albumin or DM, respectively, than bulk ZnO. In addition, serum albumin significantly increased the binding capability of nano ZnO for DM by approximately four times via the interaction of serum albumin and DM. The uptake of serum albumin- and DM-bound nano ZnO by the macrophages significantly increased DM accumulation in mice. Serum albumins play an important role in the synergistic toxicity of nano ZnO and DM. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1202-1212, 2017.

Effects of zinc oxide nanoparticles on human coronary artery endothelial cells

Inhalation of zinc oxide (ZnO) metal fumes is known to cause metal fume fever and to have systemic effects; however, the effects of ZnO nanoparticles (ZnONPs) on the cardiovascular system remain unclear. The objective of this study was to investigate the cardiovascular toxicity of ZnONPs. Human coronary artery endothelial cells (HCAECs) were exposed to ZnONPs of different sizes to investigate the cell viability, 8-hydroxy-2’-deoxyguanosine (8-OHdG), interleukin (IL)-6, nitric oxide (NO), and regulation of cardiovascular disease-related genes. Exposure of HCAECs to ZnONPs resulted in decreased cell viability and increased levels of 8-OHdG, IL-6, and NO. Downregulation of cardiovascular-associated genes was observed in response to ZnONPs in HCAECs determined by qPCR, suggesting that the calcium signaling pathway, neuroactive ligand-receptor interaction, hypertrophic cardiomyopathy, dilated cardiomyopathy, and renin-angiotensin system are important affected pathways in response to ZnONPs. Furthermore, we observed a significant response of AGTR1 to ZnONP exposure in HCAECs. Our results suggest that ZnONPs cause toxicity to HCAECs, which could be associated with cardiovascular dysfunction.