Oxidative stress and genotoxicity in Rhinella arenarum (Anura: Bufonidae) tadpoles after acute exposure to Ni-Al nanoceramics

The employ of nanomaterials (NMs) has exponentially grown due to the large number of technological advances in industrial, pharmaceutical and medical areas. That is the case of alumina (Al) nanoparticles which are extensively employed as support in heterogeneous catalysis processes. However, these NMs can cause great toxicity because of their ubiquitous properties, such as extremely small size and high specific surface area. So, it is required to assess the potential deleterious effects of these NMs on living organisms. In the present study, we analyze the oxidative stress and genotoxic potential of a nanoceramic catalyst Ni/<gamma>-Al₂O₃ (NC) and the NMs involved in their synthesis, <gamma>-Al₂O₃ support (SPC) and NiO/<gamma>-Al₂O₃ precursor (PC) on Rhinella arenarum larvae. Biomarkers of oxidative stress and genotoxic damage were measured in tadpoles exposed to 5 and 25 mg/L of each NMs for 96 h. The results indicated an inhibition of catalase activity in tadpoles exposed to both concentrations of PC and to 25 mg/L of SPC and NC. Moreover, both exposure concentrations of PC and NC significantly inhibited superoxide dismutase activity. Exposure to the three NMs caused inhibition of glutathione S-transferase activity, but there were no significant variations in reduced glutathione levels. Oxidative stress damage (lipid peroxidation) was observed in tadpoles treated with 25 mg/L PC, while the other treatments did not produce alterations. The MNs frequency significantly increased in larvae exposed to 25 mg/L PC indicating irreversible genotoxic damage. The results show that these NMs exert genotoxic effects and antioxidant defense system disruption in R. arenarum larvae.     

Aluminium oxide nanoparticles induced morphological changes,cytotoxicity and oxidative stress in Chinook salmon (CHSE‐214) cells

Aluminium oxide nanoparticles (Al₂O₃ NPs) are increasingly used in diverse applications that has raised concern about their safety. Recent studies suggested that Al₂O₃ NPs induced oxidative stress may be the cause of toxicity in algae, Ceriodaphnia dubia, Caenorhabditis elegans and Danio rerio. However, there is paucity on the toxicity of Al₂O₃ NPs on fish cell lines. The current study was aimed to investigate Al₂O₃ NPs induced cytotoxicity, oxidative stress and morphological abnormality of Chinnok salmon cells (CHSE‐214). A dose‐dependent decline in cell viability was observed in CHSE‐214 cells exposed to Al₂O₃ NPs. Oxidative stress induced by Al₂O₃ NPs in CHSE‐214 cells has resulted in the significant reduction of superoxide dismutase, catalase and glutathione in a dose‐dependent manner. However, a significant increase in glutathione sulfo‐transferase and lipid peroxidation was observed in CHSE‐214 cells exposed to Al₂O₃ NPs in a dose‐dependent manner. Significant morphological changes in CHSE‐214 cells were observed when exposed to Al₂O₃ NPs at 6, 12 and 24 h. The cells started to detach and appear spherical at 6 h followed by loss of cellular contents resulting in the shrinking of the cells. At 24 h, the cells started to disintegrate and resulted in cell death. Our data demonstrate that Al₂O₃ NPs induce cytotoxicity and oxidative stress in a dose‐dependent manner in CHSE‐214 cells. Thus, our current work may serve as a base‐line study for future evaluation of toxicity studies using CHSE‐214 cells. Copyright © 2015 John Wiley & Sons, Ltd.     

Close association of intestinal autofluorescence with the formation of severe oxidative damage in intestine of nematodes chronically exposed to Al(2)O(3)-nanoparticle

In nematodes, acute exposure (24-h) to 8.1–30.6 mg/L Al₂O₃-nanoparticles (NPs) or Al₂O₃ did not influence intestinal autofluorescence, whereas chronic exposure (10-d) to Al₂O₃-NPs at concentrations of 8.1–30.6 mg/L or Al₂O₃ at concentrations of 23.1–30.6 mg/L induced significant increases of intestinal lipofuscin accumulation, and formation of severe stress response and oxidative damage in intestines. Moreover, significant differences of intestinal autofluorescence, stress response and oxidative damage in intestines of Al₂O₃-NPs exposed nematodes from those in Al₂O₃ exposed nematodes were detected at examined concentrations. Oxidative damage in intestine was significantly correlated with intestinal autofluorescence in exposed nematodes, and oxidative damage in intestine was more closely associated with intestinal autofluorescence in nematodes exposed to Al₂O₃-NPs than exposed to Al₂O₃. Thus, chronic exposure to Al₂O₃-NPs may cause adverse effects on intestinal lipofuscin accumulation by inducing the formation of more severe oxidative stress in intestines than exposure to Al₂O₃ in nematodes.     

Toxicity of copper oxide and basic copper carbonate nanoparticles after short-term oral exposure in rats

Copper oxide (CuO) nanoparticles (NPs) and copper carbonate nanoparticles (Cu₂CO₃(OH)₂ NPs have applications as antimicrobial agents and wood preservatives: an application that may lead to oral ingestion via hand to mouth transfer. Rats were exposed by oral gavage to CuO NPs and Cu₂CO₃(OH)₂ NPs for five consecutive days with doses from 1 to 512?mg/kg and 4 to 128?mg/kg per day, respectively, and toxicity was evaluated at days 6 and 26. Both CuO NPs and Cu₂CO₃(OH)₂ NPs induced changes in hematology parameters, as well as clinical chemistry markers (e.g. increased alanine aminotransferase, ALT) indicative of liver damage For CuO NPs histopathological alterations were observed in bone marrow, stomach and liver mainly consisting of an inflammatory response, ulceration, and degeneration. Cu₂CO₃(OH)₂ NPs induced morphological alterations in the stomach, liver, intestines, spleen, thymus, kidneys, and bone marrow. In spleen and thymus lymphoid, depletion was noted that warrants further immunotoxicological evaluation. The NPs showed partial dissolution in artificial simulated stomach fluids, while in intestinal conditions, the primary particles simultaneously shrank and agglomerated into large structures. This means that both copper ions and the particulate nanoforms should be considered as potential causal agents for the observed toxicity. For risk assessment, the lowest bench mark dose (BMD) was similar for both NPs for the serum liver enzyme AST (an indication of liver toxicity), being 26.2?mg/kg for CuO NPs and 30.8?mg/kg for Cu₂CO₃(OH)₂ NPs. This was surprising since the histopathology evidence demonstrates more severe organ damage for Cu₂CO₃(OH)₂ NPs than for CuO NPs.     

Evaluation of alpha and gamma aluminum oxide nanoparticle accumulation,toxicity, and depuration in Artemia salina larvae

In this study, Artemia salina (crustacean filter feeders) larvae were used as a test model to investigate the toxicity of aluminum oxide nanoparticles (Al₂O₃ NPs) on marine microorganisms. The uptake, toxicity, and elimination of α‐Al₂O₃ (50 nm and 3.5 μm) and γ‐Al₂O₃ (5 nm and 0.4 μm) NPs were studied. Twenty‐four and ninety‐six hour exposures of different concentrations of Al₂O₃ NPs to Artemia larvae were conducted in a seawater medium. When suspended in water, Al₂O₃ NPs aggregated substantially with the sizes ranging from 6.3 nm to >0.3 µm for spherical NPs and from 250 to 756 nm for rod‐shaped NPs. The phase contrast microscope images showed that NPs deposited inside the guts as aggregates. Inductively coupled plasma mass spectrometry analysis showed that large particles (3.5 μm α‐Al₂O₃) were not taken up by Artemia, whereas fine NPs (0.4 μm γ‐Al₂O₃) and ultra‐fine NPs (5 nm γ‐Al₂O₃ and 50 nm α‐Al₂O₃) accumulated substantially. Differences in toxicity were detected as changing with NP size and morphology. The malondialdehyde levels indicated that smaller γ‐Al₂O₃ (5 nm) NPs were more toxic than larger γ‐Al₂O₃ (0.4 µm) particulates in 96 h. The highest mortality was measured as 34% in 96 h for γ‐Al₂O₃ NPs (5 nm) at 100 mg/L (LC₅₀ > 100 mg/L). γ‐Al₂O₃ NPs were more toxic than α‐Al₂O₃ NPs at all conditions. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 109–118, 2015.     

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.     

Co-exposure of iron oxide nanoparticles and glyphosate-based herbicide induces DNA damage and mutagenic effects in the guppy (Poecilia reticulata)

Iron oxide nanoparticles (IONPs) have been tested to remediate aquatic environments polluted by chemicals, such as pesticides. However, their interactive effects on aquatic organisms remain unknown. This study aimed to investigate the genotoxicity and mutagenicity of co-exposure of IONPs (γ-Fe₂O₃ NPs) and glyphosate-based herbicide (GBH) in the fish Poecilia reticulata. Thus, fish were exposed to citrate-functionalized γ-Fe₂O₃ NPs (0.3 mg L⁻¹; 5.44 nm) alone or co-exposed to γ-Fe₂O₃ NPs (0.3 mg L⁻¹) and GBH (65 and 130 μg of glyphosate L⁻¹) during 14 and 21 days. The genotoxicity (DNA damage) was analyzed by comet assay, while the mutagenicity evaluated by micronucleus test (MN test) and erythrocyte nuclear abnormalities (ENA) frequency. The co-exposure induced clastogenic (DNA damage) and aneugenic (nuclear alterations) effects on guppies in a time-dependent pattern. Fish co-exposed to NPs and GBH (130 μg glyphosate L⁻¹) showed high DNA damage when compared to NPs alone and control group, indicating synergic effects after 21 days of exposure. However, mutagenic effects (ENA) were observed in the exposure groups after 14 and 21 days. Results showed the potential genotoxic and mutagenic effects of maghemite NPs and GBH co-exposure to freshwater fish. The transformation and interaction of iron oxide nanoparticles with other pollutants, as herbicides, in the aquatic systems are critical factors in the environmental risk assessment of metal-based NPs.     

Toxicity of antimony trioxide nanoparticles on human hematopoietic progenitor cells and comparison to cell lines

Nanoparticles (NPs) are materials with one dimension in the range of 1–100 nm. The toxicity of NPs remains widely unknown and still poses concerns, due to the peculiar characteristics of materials in the nano-size range. We analyze the toxicity of seven NPs (Fe₂O₃, Fe₃O₄, Sb₂O₃, Au, TiO₂, Co, and Ag) on primary cultures of human hematopoietic progenitor cells from the bone marrow of healthy donors with CFU assays, and show that antimony oxide (Sb₂O₃) NPs and cobalt (Co) NPs have a toxic effect, while the other NPs have no effect at the tested concentrations (5, 25 and 100 μg/ml). While Co NPs suspension is toxic to both erythroid and granulocytic–monocytic precursors, Sb₂O₃ NPs at 5 μg/ml are specifically toxic to erythroid colony development, suggesting a highly selective type of toxicity. With liquid culture assays we show that Sb₂O₃ NPs impair the proliferation of erythroid progenitors, while no toxic effect is observed when Sb₂O₃ NPs are added during erythroid differentiation. CFU assays and liquid culture assays on seven human cell lines of hematopoietic origin (K562, HL-60, CEM, CEM-R, Thp-1, Jurkat, and Molt-4) show that, contrary to what observed on primary cultures of bone marrow progenitors, Sb₂O₃ NPs have no toxic effect on proliferation of any of the cell lines, raising concerns about the use of immortalized cell lines for nanotoxicology tests.     

A comparative study on the in vitro cytotoxic responses of two mammalian cell types to fullerenes,carbon nanotubes and iron oxide nanoparticles

The present study was designed to evaluate and compare the time- and dose-dependent cellular response of human periodontal ligament fibroblasts (hPDLFs), and mouse dermal fibroblasts (mDFs) to three different types of nanoparticles (NPs); fullerenes (C₆₀), single walled carbon nanotubes (SWCNTs) and iron (II,III) oxide (Fe₃O₄) nanoparticles via in vitro toxicity methods, and impedance based biosensor system. NPs were characterized according to their morphology, structure, surface area, particle size distribution and zeta potential by using transmission electron microscopy, X-ray diffraction, Brunauer–Emmett–Teller, dynamic light scattering and zeta sizer analyses. The Mössbauer spectroscopy was used in order to magnetically characterize the Fe₃O₄ NPs. The hPDLFs and mDFs were exposed to different concentrations of the NPs (0.1, 1, 10, 50 and 100?μg/mL) for predetermined time intervals (6, 24 and 48?h) under controlled conditions. Subsequently, NP exposed cells were tested for viability, membrane leakage and generation of intracellular reactive oxygen species. Additional to in vitro cytotoxicity assays, the cellular responses to selected NPs were determined in real time using an impedance based biosensor system. Taken together, information obtained from all experiments suggests that toxicity of the selected NPs is cell type, concentration and time dependent.     

Limit-test toxicity screening of selected inorganic nanoparticles to the earthworm Eisenia fetida

The toxicity of a range of inorganic (Ag, Cu, Ni, Al₂O₃, SiO₂, TiO₂ and ZrO₂) nanoparticles (NP) and their corresponding metal salt or bulk metal oxide were screened for toxicity toward the earthworm Eisenia fetida using the limit-test design (1000 mg/kg). This study provides the first ecotoxicological life history trait data on earthworms for each these NPs, as well as for AgNO₃, Al₂O₃, SiO₂, TiO₂ and ZrO₂. Significant effects were observed on survival for AgNO₃ (2.5% of controls), CuCl₂ (17.5% of controls) and NiCl₂ (32.5% of controls) and on reproduction (AgNO₃, CuCl₂, NiCl₂, Ag-NP, Cu-NP, TiO₂-NP); with total reproductive failure in both silver treatments. Ag-NP, Cu-NP and TiO₂-NP were the only NPs that caused toxic effects to E. fetida. The toxicity could not be singularly related to particle size or zeta potential or to the inherent element constituting the NPs (e.g. Ag).     

Repeated exposure to iron oxide nanoparticles causes testicular toxicity in mice

The aim of this study was to determine whether repeated exposure to iron oxide nanoparticles (Fe₂O₃‐NPs) could be toxic to mice testis. Fe₂O₃‐NPs (25 and 50 mg/kg) were intraperitoneally administered into mice once a week for 4 weeks. Our study showed that Fe₂O₃‐NPs have the ability to cross the blood‐testis barrier to get into the testis. The findings showed that exposure resulted in the accumulation of Fe₂O₃‐NPs which was evidenced from the iron content and accumulation in the testis. Furthermore, 25 and 50 mg/kg Fe₂O₃‐NPs administration increased the reactive oxygen species, lipid peroxidation, protein carbonyl content, glutathione peroxidase activity, and nitric oxide levels with a concomitant decrease in the levels of antioxidants—superoxide dismutase, catalase, glutathione, and vitamin C. Increased expression of Bax, cleaved‐caspase‐3, and cleaved‐PARP confirms apoptosis. Serum testosterone levels increased with increased concentration of Fe₂O₃‐NPs exposure. In addition, the histopathological lesions like vacuolization, detachment, and sloughing of germ cells were also observed in response to Fe₂O₃‐NPs treatment. The data from our study entailed that testicular toxicity caused by Fe₂O₃‐NPs exposure may be associated with Fe₂O₃‐NPs accumulation leading to oxidative stress and apoptosis. Therefore, precautions should be taken in the safe use of Fe₂O₃‐NPs to avoid complications in the fertility of males. Further research will unravel the possible molecular mechanisms on testicular toxicity of Fe₂O₃‐NPs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 594–608, 2017.     

Assessment of impact of α‐Fe2O3 and γ‐Fe2O3 nanoparticles on phytoplankton species Selenastrum capricornutum and Nannochloropsis oculata

In this study, the impact of alpha‐iron oxide (α‐Fe₂O₃, 20‐40 nm) and gamma iron oxide (γ‐Fe₂O₃, 20‐40 nm) nanoparticles (NPs) on phytoplankton species Selenastrum capricornutum and Nannochloropsis oculata was investigated Characterizations of the NPs were systematically carried out by TEM, dynamic light scattering, zeta potential, X‐ray diffraction, SEM, and Fourier transformation infrared spectroscopy. Acute toxicity was tested between 0.2 and 50 mg/L for each NP for a period of 72 hours exposure. γ‐Fe₂O₃ NP inhibited development of N oculata at the rate of 54% in 0.2 mg/L group with a high mortality rate of up to 82%. α‐Fe₂O₃ NPs were less toxic that induced 97% mortality on N oculata at 10 mg/L suspensions. In contrast, α‐Fe₂O₃ NP inhibited growth of S capricornutum strongly (73%) in 0.2 mg/L group. γ‐Fe₂O₃ NPs showed similar growth inhibition (72%) on S capricornutum in 10 mg/L suspensions. Despite the differential effects, the results indicated acute toxicity of α‐Fe₂O₃ and γ‐Fe₂O₃ NPs on N oculata and S capricornutum.     

Aluminum oxide nanoparticles mediated toxicity,loss of appendages in progeny of Drosophila melanogaster on chronic exposure

Abstract

Aluminum oxide (Al₂O₃) nanoparticles (NPs) have a wide number of applications which cause intentional and unintentional exposure to humans, making it important to understand the nano-bio interaction. In this study, we made an attempt to evaluate the toxic effects of Al₂O₃ NPs chronic exposure on Drosophila melanogaster. Flies were exposed to Al₂O₃ NPs at concentration 0.1 and 1?mM via ingestion throughout their lifespan and progeny flies were screened for behavioral and phenotypic abnormalities. Behavioral abnormalities in flies were recorded through larval crawling, climbing in flies and two taste testing. Chronic exposure of Al₂O₃ NPs resulted in the loss of appendages in flies resulting in five legs flies, four legs flies and absence of haltere. Exposure to Al₂O₃ NPs caused renal failure in flies as observed by swollen abdomen. Our observations clearly showed that these NPs could cause detrimental health ailments which relate to human birth deformities and kidney failure. Damage at the cellular level was studied through proteomic profiling. Three hundred and seven unique proteins were expressed on exposure to Al₂O₃ NPs and 51 proteins were differentially expressed. Enrichment analysis of differentially expressed proteins showed significant alteration in striated muscle cell differentiation, digestive tract morphogenesis, phototransduction, regulation of chromatin organization and DNA duplex unwinding.     

Mechanistic insight into reactivity and (geno)toxicity of well-characterized nanoparticles of cobalt metal and oxides

An increasing use of cobalt (Co)-based nanoparticles (NPs) in different applications and exposures at occupational settings triggers the need for toxicity assessment. Improved understanding regarding the physiochemical characteristics of Co metal NPs and different oxides in combination with assessment of toxicity and mechanisms may facilitate decisions for grouping during risk assessment. The aim of this study was to gain mechanistic insights in the correlation between NP reactivity and toxicity of three different Co-based NPs (Co, CoO, and Co₃O₄) by using various tools for characterization, traditional toxicity assays, as well as six reporter cell lines (ToxTracker) for rapid detection of signaling pathways of relevance for carcinogenicity. The results showed cellular uptake of all NPs in lung cells and induction of DNA strand breaks and oxidative damage (comet assay) by Co and CoO NPs. In-depth studies on the ROS generation showed high reactivity of Co, lower for CoO, and no reactivity of Co₃O₄ NPs. The reactivity depended on the corrosion and transformation/dissolution properties of the particles and the media highlighting the role of the surface oxide and metal speciation as also confirmed by in silico modeling. By using ToxTracker, Co NPs were shown to be highly cytotoxic and induced reporters related to oxidative stress (Nrf2 signaling) and DNA strand breaks. Similar effects were observed for CoO NPs but at higher concentrations, whereas the Co₃O₄ NPs were inactive at all concentrations tested. In conclusion, our study suggests that Co and CoO NPs, but not Co₃O₄, may be grouped together for risk assessment.     

Toxicity of binary mixtures of Al2O3 and ZnO nanoparticles toward fibroblast and bronchial epithelium cells

ABSTRACT

The objective of this study was to examine the cytotoxic effects of binary mixtures of Al₂O₃ and ZnO NPs using mouse fibroblast cells (L929) and human bronchial epithelial cells (BEAS-2B) as biological test systems. The synergistic, additive, or antagonistic behavior of the binary mixture was also investigated. In toxicity experiments, cellular morphology, mitochondrial function (MTT assay), apoptosis, nuclear size and shape, clonogenic assays, and damage based upon oxidative stress parameters were assessed under control and NPs exposure conditions. Although Abbott modeling results provided no clear evidence of the binary mixture of Al₂O₃ and ZnO NPs exhibiting synergistic toxicity, some specific assays such as apoptosis, nuclear size and shape, clonogenic assay, activities of antioxidant enzymatic enzymes catalase, superoxide dismutase, and levels of glutathione resulted in enhanced toxicity for the mixtures with 1 and 1.75 toxic units (TU) toward both cell types. Data demonstrated that co-presence of Al₂O₃ and ZnO NPs in the same environment might lead to more realistic environmental conditions. Our findings indicate cytotoxicity of binary mixtures of Al₂O₃ and ZnO NPs produced greater effects compared to toxicity of either individual compound.     

Contact (kallikrein/kinin) system activation in whole human blood induced by low concentrations of α-Fe2O3 nanoparticles

Iron-oxide nanoparticles (NPs) generated by environmental events are likely to represent health problems. α-Fe₂O₃ NPs were synthesized, characterized and tested in a model for toxicity utilizing human whole blood without added anticoagulant. MALDI-TOF of the corona was performed and activation markers for plasma cascade systems (complement, contact and coagulation systems), platelet consumption and release of growth factors, MPO, and chemokine/cytokines from blood cells were analyzed. The coronas formed on the pristine α-Fe₂O₃ NPs contained contact system proteins and they induced massive activation of the contact (kinin/kallikrein) system, as well as thrombin generation, platelet activation, and release of two pro-angiogeneic growth factors: platelet-derived growth factor and vascular endothelial growth factor, whereas complement activation was unaffected. The α-Fe₂O₃ NPs exhibited a noticeable toxicity, with kinin/kallikrein activation, which may be associated with hypotension and long-term angiogenesis in vivo, with implications for cancer, arteriosclerosis and pulmonary disease.     

In vitro toxicity screening of magnetite nanoparticles by applying mesenchymal stem cells derived from human umbilical cord lining

Despite the growing interest in nanoparticles (NPs), their toxicity has not yet been defined and the development of new strategies and predictive models are required. Human stem cells (SCs) offer a promising and innovative cell‐based model. Among SCs, mesenchymal SCs (MSCs) derived from cord lining membrane (CL) may represent a new species‐specific tool for establishing efficient platforms for primary screening and toxicity/safety testing of NPs. Superparamagnetic iron oxide NPs, including magnetite (Fe₃O₄NPs), have aroused great public health and scientific concerns despite their extensive uses. In this study, CL‐MSCs were characterized and applied for in vitro toxicity screening of Fe₃O₄NPs. Cytotoxicity, internalization/uptake, differentiation and proliferative capacity were evaluated after exposure to different Fe₃O₄NP concentrations. Data were compared with those obtained from bone marrow (BM)‐MSCs. We observed, at early passages (P3), that: (1) cytotoxicity occurred at 10 μg/mL in CL‐MSCs and 100 μg/mL in BM‐MSCs (no differences in toxicity, between CL‐ and BM‐MSCs, were observed at higher dosage, 100‐300 μg/mL); (2) cell density decrease and monolayer features loss were affected at ≥50 μg/mL in CL‐MSCs only; and (3) NP uptake was concentration‐dependent in both MSCs. After 100 μg/mL Fe₃O₄NP exposures, the capacity of proliferation was decreased (P5‐P9) in CL‐MSCs without morphology alteration. Moreover, a progressive decrease of intracellular Fe₃O₄NPs was observed over culture time. Antigen surface expression and multilineage differentiation were not influenced. These findings suggest that CL‐MSCs could be used as a reliable cell‐based model for Fe₃O₄NP toxicity screening evaluation and support the use of this approach for improving the confidence degree on the safety of NPs to predict health outcomes.     

Iron oxide nanoparticles mediated cytotoxicity via PI3K/AKT pathway: Role of quercetin

Recently Fe₂O₃ NPs (iron oxide nanoparticles) have been extensively used in medical imaging and in industry also. As a result, people are increasingly exposed day by day to those nanoparticles. The adverse effect of Fe₂O₃ NPs is not so significant at lower doses but at higher doses Fe₂O₃ NPs causes significant damage to cells. The present study investigates the cell signaling mechanism of Fe₂O₃ NPs induced oxidative stress and cytotoxicity in vitro using murine hepatocytes as the working model. In addition, the cytoprotective action of quercetin in this pathophysiology has also been investigated. Dose-dependent studies suggest that incubation of hepatocytes with 250 μg/ml Fe₂O₃ NPs for 4 h significantly decreased the cell viability and intra-cellular antioxidant ability. This study also showed that exposure to Fe₂O₃ NPs caused hepatocytes death via apoptotic pathway. Incubation of hepatocytes with quercetin (50 μmol/L) prior to 1 h of Fe₂O₃ NPs exposure protects the cells from the altering activities of antioxidant indices, cytotoxicity and apoptotic death. Results suggest that Fe₂O₃ NPs induced cellular damage and quercetin plays a protective role in Fe₂O₃ NPs induced cytotoxicity and apoptotic death.     

Phytotoxicity and biotransformation of La2O3 nanoparticles in a terrestrial plant cucumber (Cucumis sativus)

Abstract

With the increasing applications of metal-based nanoparticles in various commercial products, it is necessary to address their environmental fate and potential toxicity. In this work, we assessed the phytotoxicity of lanthanum oxide (La₂O₃) NPs to cucumber plants and determined its distribution and biotransformation in roots by TEM and EDS, as well as STXM and NEXAFS. LaCl₃ was also studied as a reference toxicant. La₂O₃ NPs and LaCl₃ were both transformed to needle-like LaPO₄ nanoclusters in the intercellular regions of the cucumber roots. In vitro experiments demonstrated that the dissolution of La₂O₃ NPs was significantly enhanced by acetic acid. Accordingly, we proposed that the dissolution of NPs at the root surface induced by the organic acids extruded from root cells played an important role in the phytotoxicity of La₂O₃ NPs. The reactions of active NPs at the nano-bio interface should be taken into account when studying the toxicity of dissolvable metal-based nanoparticles.