No evidence of the genotoxic potential of gold,silver, zinc oxide and titanium dioxide nanoparticles in the SOS chromotest

Gold nanoparticles (Au NPs), silver nanoparticles (Ag NPs), zinc oxide nanoparticles (ZnO NPs) and titanium dioxide nanoparticles (TiO₂ NPs) are widely used in cosmetic products such as preservatives, colorants and sunscreens. This study investigated the genotoxicity of Au NPs, Ag NPs, ZnO NPs and TiO₂ NPs using the SOS chromotest with Escherichia coli PQ37. The maximum exposure concentrations for each nanoparticle were 3.23 mg l^–1 for Au NPs, 32.3 mg l^–1 for Ag NPs and 100 mg l^–1 for ZnO NPs and TiO₂ NPs. Additionally, in order to compare the genotoxicity of nanoparticles and corresponding dissolved ions, the ions were assessed in the same way as nanoparticles. The genotoxicity of the titanium ion was not assessed because of the extremely low solubility of TiO₂ NPs. Au NPs, Ag NPs, ZnO NPs, TiO₂ NPs and ions of Au, Ag and Zn, in a range of tested concentrations, exerted no effects in the SOS chromotest, evidenced by maximum IF (IFmax) values of below 1.5 for all chemicals. Owing to the results, nanosized Au NPs, Ag NPs, ZnO NPs, TiO₂ NPs and ions of Au, Ag and Zn are classified as non‐genotoxic on the basis of the SOS chromotest used in this study. To the best of our knowledge, this is the first study to evaluate the genotoxicity of Au NPs, Ag NPs, ZnO NPs and TiO₂ NPs using the SOS chromotest. Copyright © 2012 John Wiley & Sons, Ltd.     

Distinct toxic interactions of TiO2 nanoparticles with four coexisting organochlorine contaminants on algae

Engineered nanoparticles are increasingly discharged into the environment. After discharge, these nanoparticles can interact with co-existing organic contaminants, resulting in a phenomena referred to as ‘joint toxicity’. This study evaluated joint toxicities of TiO₂ nanoparticles (TiO₂NPs) with four different (atrazine, hexachlorobenzene, pentachlorobenzene, and 3,3′,4,4′-tetrachlorobiphenyl) organochlorine contaminants (OCs) toward algae (Chlorella pyrenoidosa). The potential mechanisms underlying the joint toxicity were discussed, including TiO₂NPs–OC interactions, effects of TiO₂NPs and OCs on biophysicochemical properties of algae and effects of TiO₂NPs and OCs on each other’s bioaccumulation in algae. The results indicate that coexposure led to a synergistic effect on the joint toxicity for TiO₂NPs–atrazine, antagonistic effect for TiO₂NPs–hexachlorobenzene and TiO₂NPs–3,3',4,4'-tetrachlorobiphenyl, and an additive effect for TiO₂NPs–pentachlorobenzene. There was nearly no adsorption of OCs by TiO₂NPs, and the physicochemical properties of TiO₂NPs were largely unaltered by the presence of OCs. However, both OCs and NPs affected the biophysicochemical properties of algal cells and thereby influenced the cell surface binding and/or internalization. TiO₂NPs significantly increased the bioaccumulation of each OC. However, with the exception of atrazine, the bioaccumulation of TiO₂NPs decreased when used with each OC. The distinct joint toxicity outcomes were a result of the balance between the increased toxicities of OCs (increased bioaccumulations) and the altered toxicity of TiO₂NPs (bioaccumulation can either increase or decrease). These results can significantly improve our understanding of the potential environmental risks associated with NPs.     

Evaluation of cytogenotoxicity and oxidative stress parameters in male Swiss mice co-exposed to titanium dioxide and zinc oxide nanoparticles

A number of studies have investigated the adverse toxic effects of titanium dioxide (TiO₂) nanoparticles (NPs) or zinc oxide (ZnO) NPs. Information on the potential genotoxic effects of the interactions of TiO₂ NPs and ZnO NPs in vivo is lacking. Therefore, this study was designed to investigate the cytogenotoxicity of TiO₂ NPs or ZnO NPs alone or their mixtures using the bone marrow micronucleus assay, and mechanism of damage through the evaluation of oxidative stress parameters in the liver and kidney tissues of Swiss mice. Intraperitoneal administration of doses between 9.38 and 150.00 mg/kg of TiO₂ NPs or ZnO NPs or TiO₂ NPs + ZnO NPs was performed for 5 and 10 days, respectively. TiO₂ NPs alone induced a significant (P < 0.05) increase in micronucleated (Mn) polychromatic erythrocytes (PCEs) at the applied doses compared with the negative controls, with a significant difference between 5 and 10 days for TiO₂ NPs alone and TiO₂ NPs + ZnO NPs. Concurrently, TiO₂ NPs alone for 5 days and TiO₂ NPs and TiO₂ NPs + ZnO NPs for 10 days significantly (P < 0.05) decreased the percentage PCE: normochromatic erythrocyte (NCE) indicating cytotoxicity; with a significant difference between the two periods. Significant (P < 0.001) changes in the activities of superoxide dismutase (SOD) and catalase (CAT), and levels of reduced glutathione (GSH) and malondialdehyde (MDA) were observed in the liver and kidney of mice exposed to TiO₂ NPs or ZnO NPs alone or their mixtures. These results suggest that TiO₂ NPs alone was genotoxic; TiO₂ NPs and TiO₂ NPs + ZnO NPs were noticeably cytotoxic while ZnO NPs was not cytogenotoxic. The individual NPs or their mixtures induced oxidative stress.     

Cytotoxicity of TiO2 nanoparticles to mussel hemocytes and gill cells in vitro: Influence of synthesis method,crystalline structure,size and additive

Abstract

Increasing the production and applications of TiO₂ nanoparticles (NPs) has led to grow concerns about the consequences for the environment. In this study, we investigated the effects of a set of TiO₂ NPs on the viability of mussel hemocytes and gill cells using neutral red and thiazolyl tetrazolium bromide assays. For this, we compared the cytotoxicity of TiO₂ NPs (0.1–100?mg Ti/L) produced by different techniques: rutile NPs (60?nm) produced by milling and containing disodium laureth sulfosuccinate (DSLS), rutile NPs (10, 40 and 60?nm) produced by wet chemistry and anatase/rutile NPs (～100?nm) produced by plasma synthesis. The commercially available P25 anatase/rutile NPs (10–20?nm) were also tested. Exposures were performed in parallel with their respective bulk forms and the cytotoxicity of the additive DSLS was also tested. Z potential values in distilled water indicated different stabilities depending on the NP type and all NPs tested formed agglomerates/aggregates in cell culture media. In general, TiO₂ NPs showed a relatively low and dose-dependent toxicity for both cell models with the two assays tested. NPs produced by milling showed the highest effects, probably due to the toxicity of DSLS. Size-dependent toxicity was found for NPs produced by wet chemistry (10?nm?>?40?nm and 60?nm). All TiO₂ NPs tested were more toxic than bulk forms excepting for plasma produced ones, which were the least toxic TiO₂ tested. The mixture bulk anatase/rutile TiO₂ was more toxic than bulk rutile TiO₂. In conclusion, the toxicity of TiO₂ NPs varied with the mode of synthesis, crystalline structure and size of NPs and can also be influenced by the presence of additives in the suspensions.     

Zinc oxide nanoparticles induced oxidative stress in mouse bone marrow mesenchymal stem cells

Engineered nanoparticles are developed for various applications in industrial, electrical, agricultural, pharmaceutical and medical fields due to their unique properties. Nanoparticles such as TiO₂ and ZnO are widely used in cosmetics for UV protection. The toxicological investigations of ZnO NPs are highly recommended because of the increasing use in various industrial and consumer products. The toxic potential of ZnO NPs was assumed to be caused by the release of free Zn+ ions in the medium. Many of the in vivo studies suggest the toxic nature of ZnO NPs, the in vitro studies are certainly important to elucidate the mechanism of toxicity. This study examined the toxicity of ZnO NPs with the average size of 6–8?nm on the isolated mice bone marrow mesenchymal stem cells. The study focuses on the cytotoxicity and oxidative stress-mediated cellular responses upon exposure to ZnO NPs. The results indicated that the exposure to ZnO NPs significantly affects cellular viability in a dose-dependent manner. Formation of reactive oxygen species (ROS) was found to be the mechanism of cellular toxicity. The release of Zn⁺ ions from the nanoparticles, due to the instability of ZnO NPs in the acidic compartment of lysosomes, also increases the ROS generation. In addition to increased ROS production, damage of lysosomal membrane and the activation of executioner caspase-3 and caspase-7 were observed, which eventually ends in apoptosis.     

Analysis of titanium dioxide and zinc oxide nanoparticles in cosmetics

There have been rapid increases in consumer products containing nanomaterials, raising concerns over the impact of nanoparticles (NPs) to humankind and the environment, but little information has been published about mineral filters in commercial sunscreens. It is urgent to develop methods to characterize the nanomaterials in products. Titanium dioxide (TiO₂) and zinc oxide (ZnO) NPs in unmodified commercial sunscreens were characterized by laser scanning confocal microscopy, atomic force microscopy, X-ray diffraction (XRD), and transmission electron microscopy (TEM). The results showed that laser scanning confocal microscopy evaluated primary particle aggregates and dispersions but could not size NPs because of the diffraction limited resolution of optical microscopy (200 nm). Atomic force microscopy measurements required a pretreatment of the sunscreens or further calibration in phase analysis, but could not provide their elemental composition of commercial sunscreens. While XRD gave particle size and crystal information without a pretreatment of sunscreen, TEM analysis required dilution and dispersion of the commercial sunscreens before imaging. When coupled with energy-dispersive X-ray spectroscopy, TEM afforded particle size information and compositional analysis. XRD characterization of six commercial sunscreens labeled as nanoparticles revealed that three samples contained TiO₂ NPs, among which two listed ZnO and TiO₂, and displayed average particle sizes of 15 nm, 21 nm, and 78 nm. However, no nanosized ZnO particles were found in any of the samples by XRD. In general, TEM can resolve nanomaterials that exhibit one or more dimensions between 1 nm and 100 nm, allowing the identification of ZnO and TiO₂ NPs in all six sunscreens and ZnO/TiO₂ mixtures in two of the samples. Overall, the combination of XRD and TEM was suitable for analyzing ZnO and TiO₂ NPs in commercial sunscreens.     

Acute and chronic toxicity of nano-scale TiO2 particles to freshwater fish,cladocerans, and green algae,and effects of organic and inorganic substrate on TiO2 toxicity

This research evaluated the toxicity of TiO₂ nanoparticles to freshwater aquatic organisms and the effects of organic and inorganic material on TiO₂ toxicity. The fathead minnow was much less acutely sensitive to TiO₂ (LC50 500 mg/l and higher) than Ceriodaphnia dubia and Daphnia pulex (mean LC50 values 7.6 and 9.2 mg/l, respectively). Total organic carbon levels of 1.5 mg/l decreased TiO₂ acute toxicity to C. dubia (LC50 > 100 mg/l), but kaolinite clay decreased TiO₂ toxicity to a lesser extent. In chronic toxicity tests, the green algae Pseudokirchneriella subcapitata was more sensitive to TiO₂ (IC25 1–2 mg/l) than C. dubia (IC25 9.4–26.4 mg/l) and the fathead minnow (IC25 values over 340 mg/l). Study results indicate that the specific organisms exposed and the effects of water quality parameters on TiO₂ toxicity should be considered in hazard evaluations of this nanoparticle.     

Comparative study of ZnO and TiO2 nanoparticles: physicochemical characterisation and toxicological effects on human colon carcinoma cells

Abstract

Despite human gastrointestinal exposure to nanoparticles (NPs), data on NPs toxicity in intestinal cells are quite scanty. In this study we evaluated the toxicity induced by zinc oxide (ZnO) and titanium dioxide (TiO₂) NPs on Caco-2 cells. Only ZnO NPs produced significant cytotoxicity, evaluated by two different assays. The presence of foetal calf serum in culture medium significantly reduced ZnO NPs toxicity as well as ion leakage and NP-cell interaction. The two NPs increased the intracellular amount of reactive oxygen species (ROS) after 6 h treatment. However, only ZnO NPs increased ROS and induced IL-8 release both after 6 and 24 h. Experimental data indicate a main role of chemical composition and solubility in ZnO NPs toxicity. Moreover our results suggest a key role of oxidative stress in ZnO NPs cytotoxicity induction related both to ion leakage and to cell interaction with NPs in serum-free medium.     

Cytotoxicity of Au,ZnO and SiO2 NPs using in vitro assays with mussel hemocytes and gill cells: Relevance of size,shape and additives

Metal-bearing nanoparticles (NPs) possess unique physico-chemical characteristics that make them useful for an increasing number of industrial products and applications, but could also confer them a higher toxicity due to their higher reactivity compared to bulk forms of the same materials. There is a considerable interest in the use of in vitro techniques in environmentally relevant species, such as marine mussels, to evaluate NPs toxicity. In the present work, mussel hemocytes and gill cells were used to assess the potential toxic effects of Au, ZnO and SiO₂ NPs with different sizes and shapes in parallel with their respective ionic and bulk forms and additives used in the NPs preparations. Cytotoxicity (neutral red and MTT assays) was screened at a wide range of concentrations, and LC50 values were calculated. Uptake of fluorescently labeled SIO₂ NPs of 27?nm by hemocytes was also investigated. Au, ZnO and SiO₂ NPs were less toxic than the corresponding ionic forms but more toxic than the bulk forms. ZnO NPs were the most toxic NPs tested which could be related with their capacity to release free ions. SiO₂ NPs were not taken up by hemocytes and were not toxic to either hemocytes or gill cells. Size-dependent toxicity was found for Au NPs. Shape influenced the cytotoxicity of ZnO NPs. Finally, the presence of the additives Na-citrate and Ecodis P90 contributed to the toxicity of Au and ZnO NPs, respectively. As a general conclusion, solubility appears to play a key role in NPs toxicity to mussel cells.     

Titanium dioxide nanoparticles prime a specific activation state of macrophages

Titanium dioxide nanoparticles (TiO₂ NPs) are widely used in foods, cosmetics, and medicine. Although the inhalation toxicity of TiO₂ NPs has been studied, the potential adverse effects of oral exposure of low-dose TiO₂ NPs are largely unclear. Herein, with macrophage cell lines, primary cells, and mouse models, we show that TiO₂ NPs prime macrophages into a specific activation state characterized by excessive inflammation and suppressed innate immune function. After a month of dietary exposure in mice or exposure in vitro to TiO₂ NPs (10 and 50?nm), the expressions of pro-inflammatory genes in macrophages were increased, and the expressions of anti-inflammatory genes were decreased. In addition, for macrophages exposed to TiO₂ NPs in vitro and in vivo, their chemotactic, phagocytic, and bactericidal activities were lower. This imbalance in the immune system could enhance the susceptibility to infections. In mice, after a month of dietary exposure to low doses of TiO₂ NPs, an aggravated septic shock occurred in response to lipopolysaccharide challenge, leading to elevated levels of inflammatory cytokines in serum and reduced overall survival. Moreover, TLR4-deficient mice and primary macrophages, or TLR4-independent stimuli, showed less response to TiO₂ NPs. These results demonstrate that TiO₂ NPs induce an abnormal state of macrophages characterized by excessive inflammation and suppressed innate immune function in a TLR4-dependent manner, which may suggest a potential health risk, particularly for those with additional complications, such as bacterial infections.     

Influence of silver and titanium dioxide nanoparticles on in vitro blood-brain barrier permeability

An in vitro blood-brain barrier (BBB) model being composed of co-culture with endothelial (bEnd.3) and astrocyte-like (ALT) cells was established to evaluate the toxicity and permeability of Ag nanoparticles (AgNPs; 8 nm) and TiO₂ nanoparticles (TiO₂NPs; 6 nm and 35 nm) in normal and inflammatory central nervous system. Lipopolysaccharide (LPS) was pre-treated to simulate the inflammatory responses. Both AgNPs and Ag ions can decrease transendothelial electrical resistance (TEER) value, and cause discontinuous tight junction proteins (claudin-5 and zonula occludens-1) of BBB. However, only the Ag ions induced inflammatory cytokines to release, and had less cell-to-cell permeability than AgNPs, which indicated that the toxicity of AgNPs was distinct from Ag ions. LPS itself disrupted BBB, while co-treatment with AgNPs and LPS dramatically enhanced the disruption and permeability coefficient. On the other hand, TiO₂NPs exposure increased BBB penetration by size, and disrupted tight junction proteins without size dependence, and many of TiO₂NPs accumulated in the endothelial cells were observed. This study provided the new insight of toxic potency of AgNPs and TiO₂NPs in BBB.     

In vitro evaluation of the toxicity and underlying molecular mechanisms of Janus Fe3O4‐TiO2 nanoparticles in human liver cells

Recent studies show that Janus Fe₃O₄‐TiO₂ nanoparticles (NPs) have potential applications as a multifunctional agent of magnetic resonance imaging (MRI) and photodynamic therapy (PDT) for the diagnosis and therapy of cancer. However, little work has been done on their biological effects. To evaluate the toxicity and underlying molecular mechanisms of Janus Fe₃O₄‐TiO₂ nanoparticles, an in vitro study using a human liver cell line HL‐7702 cells was conducted. For comparison, the Janus Fe₃O₄‐TiO₂ NPs parent material TiO₂ NPs was also evaluated. Results showed that both Fe₃O₄‐TiO₂ NPs and TiO₂ NPs decreased cell viability and ATP levels when applied in treatment, but increased malonaldehyde (MDA) and reactive oxygen species (ROS) generation. Mitochondria JC‐1 staining assay showed that mitochondrial membrane permeability injury occurred in both NPs treated cells. Cell viability analysis showed that TiO₂ NPs induced slightly higher cytotoxicity than Fe₃O₄‐TiO₂ NPs in HL7702 cells. Western blotting indicated that both TiO₂ NPs and Fe₃O₄‐TiO₂ NPs could induce apoptosis, inflammation, and carcinogenesis related signal protein alterations. Comparatively, Fe₃O₄‐TiO₂ NPs induced higher signal protein expressions than TiO₂ NPs under a high treatment dose. However, under a low dose (6.25 μg/cm²), neither NPs had any significant toxicity on HL7702 cells. In addition, our results suggest both Fe₃O₄‐TiO₂ NPs and TiO₂ NPs could induce oxidative stress and have a potential carcinogenetic effect in vitro. Further studies are needed to elaborate the detailed mechanisms of toxicity induced by a high dose of Fe₃O₄‐TiO₂ NPs.     

In vitro screening of metal oxide nanoparticles for effects on neural function using cortical networks on microelectrode arrays

Nanoparticles (NPs) may translocate to the brain following inhalation or oral exposures, yet higher throughput methods to screen NPs for potential neurotoxicity are lacking. The present study examined effects of 5 CeO₂ (5– 1288?nm), and 4 TiO₂ (6–142?nm) NPs and microparticles (MP) on network function in primary cultures of rat cortex on 12 well microelectrode array (MEA) plates. Particles were without cytotoxicity at concentrations ≤50?µg/ml. After recording 1?h of baseline activity prior to particle (3–50?µg/ml) exposure, changes in the total number of spikes (TS) and # of active electrodes (#AEs) were assessed 1, 24, and 48?h later. Following the 48?h recording, the response to a challenge with the GABA_A antagonist bicuculline (BIC; 25?µM) was assessed. In all, particles effects were subtle, but 69?nm CeO₂ and 25?nm TiO₂ NPs caused concentration-related decreases in TS following 1?h exposure. At 48?h, 5 and 69?nm CeO₂ and 25 and 31?nm TiO₂ decreased #AE, while the two MPs increased #AEs. Following BIC, only 31?nm TiO₂ produced concentration-related decreases in #AEs, while 1288?nm CeO₂ caused concentration-related increases in both TS and #AE. The results indicate that some metal oxide particles cause subtle concentration-related changes in spontaneous and/or GABA_A receptor-mediated neuronal activity in vitro at times when cytotoxicity is absent, and that MEAs can be used to screen and prioritize nanoparticles for neurotoxicity hazard.     

Formulation and characterization of tobramycin-chitosan nanoparticles coated with zinc oxide nanoparticles

Herein we describe the preparation, characterization and the antibacterial effect of Tobramycin-chitosan nanoparticles (TOB-CS NPs) coated with zinc oxide nanoparticles (ZnO NPs). Four formulations of TOB-CS NPs (A-D) were prepared to study the effect of experimental variables on the NPs behavior. Two formulations of ZnO NPs were prepared using the solvothermal and the precipitation methods (ZnO₁ and ZnO₂), and then characterized. TOB-CS NPs (Formula d) was coated with the ZnO₁. Moreover, the antibacterial activity of TOB-CS NPs, ZnO NPs and the coated nanoparticles against S. aureus and E. coli was examined. Changing the variables in preparing TOB-CS NPs resulting in variabilities in sizes (297.6–1116.3 nm), charges (+8.29–+39.00 mV), entrapment (51.95–90.60%). Further, TOB release was sustained over four days. ZnO NPs have sizes of 47.44 and 394.4 nm and charges of ?62.3 and 89.4 mV when prepared by solvothermal and precipitation technique, respectively. Coated TOB-CS NPs had a size of 342 nm, a charge of +4.39 and released 100 µg/ mL of the drug after four days. The antimicrobial activity of TOB-CS NPs was lower than free TOB against S. aureus and E. coli. The coated NPs showed higher antimicrobial effect in comparison to formula D and ZnO₁. In conclusion, coating TOB-CS NPs with ZnO NPs exhibited a great antibacterial effect that may be sustained for days.     

Potential impact of metal oxide nanoparticles on the immune system: The role of integrins,L-selectin and the chemokine receptor CXCR4

The impact of metal oxide nanoparticles (NPs) on the immune system has been studied in vitro using human peripheral blood lymphocytes (PBLs). Metal oxide NPs (ZnO, CeO₂, TiO₂ and Al₂O₃) induced changes in the expression levels of adhesion molecules and the C-X-C chemokine receptor type 4 (CXCR4) in these cells. Proliferation studies were carried out with CFSE in response to PHA, finding an increase in T-cell proliferation upon cell exposure to TiO₂ and Al₂O₃ NPs. For ZnO NPs, a decrease in the chemotactic response to SDF-1α was observed. No changes were found in basophil activation and leukocyte oxidative burst after phagocytosis. Despite the absence of cytotoxicity, metal oxide NPs are not inert; they alter the expression levels of adhesion molecules and chemokine receptors, key actors in the immune response, and affect important cell functions such as T-cell proliferative response to mitogens and chemotaxis.From the Clinical EditorThis study demonstrates the immune-modulating effects of four different metal nanoparticles in a human peripheral blood lymphocyte model system. These effects were clearly present even though these nanoparticles did not display cytotocity in ex vivo experiments.     

Inflammatory response in human alveolar epithelial cells after TiO2 NPs or ZnO NPs exposure: Inhibition of surfactant protein A expression as an indicator for loss of lung function

The increasing use of metal oxide nanoparticles (MONPs) as TiO₂ NPs or ZnO NPs has led to environmental release and human exposure. The respiratory system, effects on lamellar bodies and surfactant protein A (SP-A) of pneumocytes, can be importantly affected. Exposure of human alveolar epithelial cells (A549) induced differential responses; a higher persistence of TiO₂ in cell surface and uptake (measured by Atomic Force Microscopy) and sustained inflammatory response (by means of TNF-α, IL-10, and IL-6 release) and ROS generation were observed, whereas ZnO showed a modest response and low numbers in cell surface. A reduction in SP-A levels at 24 h of exposure to TiO₂ NPs (concentration-dependent) or ZnO NPs (the higher concentration) was also observed, reversed by blocking the inflammatory response (by the inhibition of IL-6). Loss of SP-A represents a relevant target of MONPs-induced inflammatory response that could contribute to cellular damage and loss of lung function.     

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?2 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?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?相似文献   

Acute exposure to ZnO nanoparticles induces autophagic immune cell death

Abstract

The increasing risk of incidental exposure to nanomaterials has led to mounting concerns regarding nanotoxicity. Zinc oxide nanoparticles (ZnO NPs) are produced in large quantities and have come under scrutiny due to their capacity to cause cytotoxicity in vitro and potential to cause harm in vivo. Recent evidence has indicated that ZnO NPs promote autophagy in cells; however, the signaling pathways and the role of ion release inducing toxicity remain unclear. In this study, we report that ZnO NPs are immunotoxic to primary and immortalized immune cells. Importantly, such immunotoxicity is observed in mice in vivo, since death of splenocytes is seen after intranasal exposure to ZnO NPs. We determined that ZnO NPs release free Zn²⁺ that can be taken up by immune cells, resulting in cell death. Inhibiting free Zn²⁺ ions in solution with EDTA or their uptake with CaCl₂ abrogates ZnO NP-induced cell death. ZnO NP-mediated immune cell death was associated with increased levels of intracellular reactive oxygen species (ROS). ZnO NP death was not due to apoptosis, necroptosis or pyroptosis. Exposure of immune cells to ZnO NPs resulted in autophagic death and increased levels of LC3A, an essential component of autophagic vacuoles. Accordingly, ZnO NP-mediated upregulation of LC3A and induction of immune cell death were inhibited by blocking autophagy and ROS production. We conclude that release of Zn²⁺ from ZnO NPs triggers the production of excessive intracellular ROS, resulting in autophagic death of immune cells. Our findings suggest that exposure to ZnO NPs has the potential to impact host immunity.     

Mechanism of TiO2 nanoparticle‐induced neurotoxicity in zebrafish (Danio rerio)

Zebrafish (Danio rerio) has been used historically for evaluating the toxicity of environmental and aqueous toxicants, and there is an emerging literature reporting toxic effects of manufactured nanoparticles (NPs) in zebrafish embryos. Few researches, however, are focused on the neurotoxicity on adult zebrafish after subchronic exposure to TiO₂ NPs. This study was designed to evaluate the morphological changes, alterations of neurochemical contents, and expressions of memory behavior‐related genes in zebrafish brains caused by exposures to 5, 10, 20, and 40 μg/L TiO₂ NPs for 45 consecutive days. Our data indicated that spatial recognition memory and levels of norepinephrine, dopamine, and 5‐hydroxytryptamine were significantly decreased and NO levels were markedly elevated, and over proliferation of glial cells, neuron apoptosis, and TiO₂ NP aggregation were observed after low dose exposures of TiO₂ NPs. Furthermore, the low dose exposures of TiO₂ NPs significantly activated expressions of C‐fos, C‐jun, and BDNF genes, and suppressed expressions of p38, NGF, CREB, NR1, NR2ab, and GluR2 genes. These findings imply that low dose exposures of TiO₂ NPs may result in the brain damages in zebrafish, provide a developmental basis for evaluating the neurotoxicity of subchronic exposure, and raise the caution of aquatic application of TiO₂ NPs. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 163–175, 2016.