Effects of cerium oxide nanoparticles on adenine-induced chronic kidney disease model rats.

AIM: Cerium oxide, particularly in nanoparticle form (nanoceria), has been investigated for biomedical applications as a promising new agent for treating several pathologies. The aim of the present study was to characterize the pharmacologic effects of nanoceria in an animal model of chronic kidney disease. METHODS: We created the chronic kidney disease animal model by feeding rats a 0.25% adenine diet. Male Wistar rats were divided into five groups: normal diet, 0.25% adenine diet, or adenine diet containing three different doses or durations of nanoceria treatment. Blood was collected weekly from the tail veins of each rat and analyzed for renal function markers. After 5 weeks, various biochemical markers in serum, plasma, and urine were also analyzed. RESULTS: In the adenine-treated group, body weight was significantly decreased, and the kidneys lost much of their healthy reddish color and became lumpy and white in appearance. In addition, levels of serum creatinine, blood urea nitrogen, and plasma uremic toxins were significantly increased in adenine-treated rats compared with controls. Renal functional and structural damage in adenine diet model rats tended to be ameliorated by nanoceria ingestion. The high-dose cerium-treated group maintained reddish areas in the kidneys, and the increases in biomarker levels of creatinine, blood urea nitrogen, and inorganic phosphorus were markedly reduced, regardless of treatment duration. CONCLUSIONS: Ingestion of nanoceria may be effective for improving or preventing renal damage caused by adenine. Geriatr Gerontol Int 2024; 24: 88-95.

Combinatory Effects of Cerium Dioxide Nanoparticles and Acetaminophen on the Liver-A Case Study of Low-Dose Interactions in Human HuH-7 Cells.

The interactions between pharmaceuticals and nanomaterials and its potentially resulting toxicological effects in living systems are only insufficiently investigated. In this study, two model compounds, acetaminophen, a pharmaceutical, and cerium dioxide, a manufactured nanomaterial, were investigated in combination and individually. Upon inhalation, cerium dioxide nanomaterials were shown to systemically translocate into other organs, such as the liver. Therefore we picked the human liver cell line HuH-7 cells as an in vitro system to investigate liver toxicity. Possible synergistic or antagonistic metabolic changes after co-exposure scenarios were investigated. Toxicological data of the water soluble tetrazolium (WST-1) assay for cell proliferation and genotoxicity assessment using the Comet assay were combined with an untargeted as well as a targeted lipidomics approach. We found an attenuated cytotoxicity and an altered metabolic profile in co-exposure experiments with cerium dioxide, indicating an interaction of both compounds at these endpoints. Single exposure against cerium dioxide showed a genotoxic effect in the Comet assay. Conversely, acetaminophen exhibited no genotoxic effect. Comet assay data do not indicate an enhancement of genotoxicity after co-exposure. The results obtained in this study highlight the advantage of investigating co-exposure scenarios, especially for bioactive substances.

Metal Homeostasis and Gas Exchange Dynamics in Pisum sativum L. Exposed to Cerium Oxide Nanoparticles.

Cerium dioxide nanoparticles are pollutants of emerging concern. They are rarely immobilized in the environment. This study extends our work on Pisum sativum L. as a model plant, cultivated worldwide, and is well suited for investigating additive interactions induced by nanoceria. Hydroponic cultivation, which prompts accurate plant growth control and three levels of CeO2 supplementation, were applied, namely, 100, 200, and 500 mg (Ce)/L. Phytotoxicity was estimated by fresh weights and photosynthesis parameters. Additionally, Ce, Cu, Zn, Mn, Fe, Ca, and Mg contents were analyzed by high-resolution continuum source atomic absorption and inductively coupled plasma optical emission techniques. Analysis of variance has proved that CeO2 nanoparticles affected metals uptake. In the roots, it decreased for Cu, Zn, Mn, Fe, and Mg, while a reversed process was observed for Ca. The latter is absorbed more intensively, but translocation to above-ground parts is hampered. At the same time, nanoparticulate CeO2 reduced Cu, Zn, Mn, Fe, and Ca accumulation in pea shoots. The lowest Ce concentration boosted the photosynthesis rate, while the remaining treatments did not induce significant changes. Plant growth stimulation was observed only for the 100 mg/L. To our knowledge, this is the first study that demonstrates the effect of nanoceria on photosynthesis-related parameters in peas.

A systematic review of the interaction and effects generated by antimicrobial metallic substituents in bone tissue engineering.

Metallic elements are one of the key components of human physiology, which are required for basic cellular and extracellular functions. Herein, we provide insight into the bioactive metallic dopants silver (Ag), zinc (Zn), copper (Cu), magnesium (Mg) and ceria (Ce), which provide resistance against human pathogenic bacteria, and summarise the pathways for their generated effects crucial for osteogenic activity in an antibacterial environment and bone regeneration. Although most of these elements interact with genetic material, resulting in denaturation to produce apoptosis of pathogenic cells, some create adverse effects in the cellular matrix, which interfere with normal cellular metabolism and inhibit cellular activity, reducing the further growth and formation of bacterial colonies. Furthermore, although remarkable antibacterial activity has been recorded, bacterial cells have developed pathways and transporter proteins that remove the excess of these antibacterial elements from the cellular matrix. Thus, a discussion of these reported pathways as limitations is presented to find more novel modes of administration of these elements since they show good biocompatibility and are non-cytotoxic at certain release concentrations. As a cofactor of several enzymes, it is worth noting that some of these elements not only help in the metabolism of bone, but also activate the genetic pathways that regulate the formation of and maintain the factors that support new bone. The choice of incorporating these materials in ionic or nanoparticle form depends on the target substrate since they exhibit different mechanisms of action and even produce selective effects depending on their physical properties.

Evaluation of neurological effects of cerium dioxide nanoparticles doped with different amounts of zirconium following inhalation exposure in mouse models of Alzheimer's and vascular disease.

Increasing evidence from toxicological and epidemiological studies indicates that the brain is an important target for ambient (ultrafine) particles. Disturbance of redox-homeostasis and inflammation in the brain are proposed as possible mechanisms that can contribute to neurotoxic and neurodegenerative effects. Whether and how engineered nanoparticles (NPs) may cause neurotoxicity and promote neurodegenerative diseases such as Alzheimer's disease (AD) is largely unstudied. We have assessed the neurological effects of subacute inhalation exposures (4 mg/m3 for 3 h/day, 5 days/week for 4 weeks) to cerium dioxide (CeO2) NPs doped with different amounts of zirconium (Zr, 0%, 27% and 78%), to address the influence of particle redox-activity in the 5xFAD transgenic mouse model of AD. Four weeks post-exposure, effects on behaviour were evaluated and brain tissues were analysed for amyloid-ß plaque formation and reactive microglia (Iba-1 staining). Behaviour was also evaluated in concurrently exposed non-transgenic C57BL/6J littermates, as well as in Western diet-fed apolipoprotein E-deficient (ApoE-/-) mice as a model of vascular disease. Markers of inflammation and oxidative stress were evaluated in brain cortex. The brains of the NP-exposed 5xFAD mice revealed no accelerated amyloid-ß plaque formation. No significant treatment-related behaviour impairments were observed in the healthy C57BL/6J mice. In the 5xFAD and ApoE-/- models, the NP inhalation exposures did not affect the alternation score in the X-maze indicating absence of spatial working memory deficits. However, following inhalation exposure to the 78% Zr-doped CeO2 NPs changes in forced motor performance (string suspension) and exploratory motor activity (X-maze) were observed in ApoE-/- and 5xFAD mice, respectively. Exposure to the 78% doped NPs also caused increased cortical expression of glial fibrillary acidic protein (GFAP) in the C57BL/6J mice. No significant treatment-related changes neuroinflammation and oxidative stress were observed in the 5xFAD and ApoE-/- mice. Our study findings reveal that subacute inhalation exposure to CeO2 NPs does not accelerate the AD-like phenotype of the 5xFAD model. Further investigation is warranted to unravel whether the redox-activity dependent effects on motor activity as observed in the mouse models of AD and vascular disease result from specific neurotoxic effects of these NPs.

Silver Sulfadiazine and Cerium Nitrate in Ischemic Skin Necrosis of the Leg and Foot: Results of a Prospective Randomized Controlled Study.

Flammacerium is a topical treatment composed of silver sulfadiazine and cerium nitrate initially used in burns. The objective was to assess the effectiveness of silver sulfadiazine and cerium nitrate on ischemic necrosis wounds of the lower limb as an alternative to amputation for a period of 12 weeks. Patients were prospectively randomized to receive silver sulfadiazine and cerium nitrate or standard care. Patients included adults with an ischemic wound of the lower limb, with necrosis covering over at least 50%. Critical ischemia limb was confirmed by an ankle-brachial index <0.7 or >1.3 with radiological confirmation. Patient demographic data, amputations procedures, wound area, Visual Analogue Scale pain rating, clinical infection, and adverse events were recorded. Fifty patients, 34 males and 16 females, were recruited between January 2010 and April 2014, 25 in each group. The mean age was 75.14 years (±11.64). Nine amputations (36%) occurred in each group. Amputation-free survival was superior in the active treatment group versus the standard group (169 393 days, 95% confidence interval = 134.926-203.861, vs 169 393 days, 95% confidence interval = 134.926-203.861). It was not statistically significant (log-rank, P = .958). Wound area reduction between both groups was not statistically different ( P = .651). Less adverse events of the lower limb occurred in the active treatment group ( P = .001). Our study showed that silver sulfadiazine and cerium nitrate is not inferior to standardized care on ischemic necrotic wounds of the lower extremity. Further studies are still needed to confirm its effectiveness.

In vivo-induced size transformation of cerium oxide nanoparticles in both lung and liver does not affect long-term hepatic accumulation following pulmonary exposure.

Recent findings show that cerium oxide (CeO2) nanoparticles may undergo in vivo-induced size transformation with the formation of smaller particles that could result in a higher translocation following pulmonary exposure compared to virtually insoluble particles, like titanium dioxide (TiO2). Therefore, we compared liver deposition of CeO2 and TiO2 nanoparticles of similar primary sizes 1, 28 or 180 days after intratracheal instillation of 162 µg of NPs in female C57BL/6 mice. Mice exposed to 162 µg CeO2 or TiO2 nanoparticles by intravenous injection or oral gavage were included as reference groups to assess the amount of NPs that reach the liver bypassing the lungs and the translocation of NPs from the gastrointestinal tract to the liver, respectively. Pulmonary deposited CeO2 nanoparticles were detected in the liver 28 and 180 days post-exposure and TiO2 nanoparticles 180 days post-exposure as determined by darkfield imaging and by the quantification of Ce and Ti mass concentration by inductively coupled plasma-mass spectrometry (ICP-MS). Ce and Ti concentrations increased over time and 180 days post-exposure the translocation to the liver was 2.87 ± 3.37% and 1.24 ± 1.98% of the initial pulmonary dose, respectively. Single particle ICP-MS showed that the size of CeO2 nanoparticles in both lung and liver tissue decreased over time. No nanoparticles were detected in the liver following oral gavage. Our results suggest that pulmonary deposited CeO2 and TiO2 nanoparticles translocate to the liver with similar calculated translocation rates despite their different chemical composition and shape. The observed particle size distributions of CeO2 nanoparticles indicate in vivo processing over time both in lung and liver. The fact that no particles were detected in the liver following oral exposure showed that direct translocation of nanoparticles from lung to the systemic circulation was the most important route of translocation for pulmonary deposited particles.

Fate of inhaled Nano-CeO2 revisited: Predicting the unpredictable.

This paper compares the pulmonary kinetics of inhaled nano-CeO2 from two published repeated inhalation studies of 13-week duration in rats. This database was used to predict the outcome of a 2-year chronic inhalation study with a focus on the no observed adverse effect level (NOAEL) and range of conditions causing kinetic lung overload up to and beyond the maximum tolerated dose (MTD). Modeling identified nano-CeO2 to be typical poorly soluble, low-toxicity particles (PSLTs), although even partial dissolution may lead to interactions with pulmonary surfactant, eventually resulting in pulmonary phospholipidosis and fibrosis. An earlier model published in 2011 to surpass and replace the traditional Morrow approach focused on kinetic lung overload to simulate the pulmonary fate of inhaled micron-sized PSLT in rats. By misunderstanding or inaction, this earlier model was overlooked as a better hypothesis-based model for dosimetry selection of long-term inhalation studies with the aim of reducing study repetition and animal numbers. While it appears that the primary adverse pathway of the earlier model also applies to nano-CeO2, the updated model proposed here also accounts for phospholipid-like additional volume loads. Data from a heralded 2-year inhalation study in rats are not yet available, but the study was traditionally modeled to predict the toxicological NOAEL and MTD hallmarks. When completed, this study's data will clarify whether the advanced 21st century modeling proposed here may be more advantageous for design and execution of inhalation studies, compared to simplistic and outdated gross overload models.

Detection of DNA Damage Induced by Cerium Dioxide Nanoparticles: From Models to Molecular Mechanism Activated.

This chapter will present an original effort to summarize the relevant data about the cyto-genotoxicity induced by cerium dioxide nanoparticles (nanoceria) in physiologically (in vivo and in vitro) relevant models. In this way, this chapter should be extremely useful to everyone who wants to plan their research and publishing their results. Massive application of nanoceria at different fields is increasing year after year, and it is urgent to address and discuss their use and its safety-related issues. Specifically, the nanoceria are being designed for nanomedicine, cosmetics, polishing materials and additives for automotive fuels. Their unique properties include the ability to absorb UV radiation, antioxidant potential and the rapid exchange of valence between Ce4+ and Ce3+ ions associated to oxygen storage. In this chapter, the state of the art regarding the physicochemical properties of nanoceria, nanogenotoxicity detected by in vitro and in vivo systems and the general aspects in the cyto-genotoxic mechanism of nanoceria are summarized. The cyto-genotoxicity will be discussed in terms of evaluations by Comet assay, Micronucleus test, DNA damage response and oxidative stress detected in cell culture systems and in vivo test. We also described the dose dependent cyto-genotoxic effects of nanoceria based on their physical-chemical nature. Paradoxically, these particles have been characterized as either pro-oxidant or anti-oxidant in dependence of microenvironment and physiological conditions such as pH. Finally, this chapter will contribute to point out aspects of the development of new in vitro and in vivo methodologies to detect cyto-genotoxic effects of the nanoceria.

Cerium oxide and barium sulfate nanoparticle inhalation affects gene expression in alveolar epithelial cells type II.

BACKGROUND: Understanding the molecular mechanisms of nanomaterial interacting with cellular systems is important for appropriate risk assessment. The identification of early biomarkers for potential (sub-)chronic effects of nanoparticles provides a promising approach towards cost-intensive and animal consuming long-term studies. As part of a 90-day inhalation toxicity study with CeO2 NM-212 and BaSO4 NM-220 the present investigations on gene expression and immunohistochemistry should reveal details on underlying mechanisms of pulmonary effects. The role of alveolar epithelial cells type II (AEII cells) is focused since its contribution to defense against inhaled particles and potentially resulting adverse effects is assumed. Low dose levels should help to specify particle-related events, including inflammation and oxidative stress. RESULTS: Rats were exposed to clean air, 0.1, 0.3, 1.0, and 3.0 mg/m3 CeO2 NM-212 or 50.0 mg/m3 BaSO4 NM-220 and the expression of 391 genes was analyzed in AEII cells after one, 28 and 90 days exposure. A total number of 34 genes was regulated, most of them related to inflammatory mediators. Marked changes in gene expression were measured for Ccl2, Ccl7, Ccl17, Ccl22, Ccl3, Ccl4, Il-1α, Il-1ß, and Il-1rn (inflammation), Lpo and Noxo1 (oxidative stress), and Mmp12 (inflammation/lung cancer). Genes related to genotoxicity and apoptosis did not display marked regulation. Although gene expression was less affected by BaSO4 compared to CeO2 the gene pattern showed great overlap. Gene expression was further analyzed in liver and kidney tissue showing inflammatory responses in both organs and marked downregulation of oxidative stress related genes in the kidney. Increases in the amount of Ce were measured in liver but not in kidney tissue. Investigation of selected genes on protein level revealed increased Ccl2 in bronchoalveolar lavage of exposed animals and increased Lpo and Mmp12 in the alveolar epithelia. CONCLUSION: AEII cells contribute to CeO2 nanoparticle caused inflammatory and oxidative stress reactions in the respiratory tract by the release of related mediators. Effects of BaSO4 exposure are low. However, overlap between both substances were detected and support identification of potential early biomarkers for nanoparticle effects on the respiratory system. Signs for long-term effects need to be further evaluated by comparison to a respective exposure setting.

Dermal transfer and environmental release of CeO2 nanoparticles used as UV inhibitors on outdoor surfaces: Implications for human and environmental health.

A major area of growth for "nano-enabled" consumer products have been surface coatings, including paints stains and sealants. Ceria (CeO2) nanoparticles (NPs) are of interest as they have been used as additives in these these products to increase UV resistance. Currently, there is a lack of detailed information on the potential release, and speciation (i.e., ion vs. particle) of CeO2 NPs used in consumer-available surface coatings during intended use scenarios. In this study, both Micronized-Copper Azole pressure-treated lumber (MCA), and a commercially available composite decking were coated with CeO2 NPs dispersed in Milli-Q water or wood stain. Coated surfaces were divided into two groups. The first was placed outdoors to undergo environmental weathering, while the second was placed indoors to act as experimental controls. Both weathered surfaces and controls were sampled over a period of 6months via simulated dermal contact using methods developed by the Consumer Product Safety Commission (CPSC). The size and speciation of material released was determined through sequential filtration, total metals analysis, X-Ray Absorption Fine Structure Spectroscopy, and electron microscopy. The total ceria release from MCA coated surfaces was found to be dependent on dispersion matrix with aqueous applications releasing greater quantities of CeO2 than stain based applications, 66±12mg/m2 and 36±7mg/m2, respectively. Additionally, a substantial quantity of CeO2 was reduced to Ce(III), present as Ce(III)-organic complexes, over the 6-month experimental period in aqueous based applications.

Synergistic role of nanoceria on the ability of tobacco smoke to induce carcinogenic hallmarks in lung epithelial cells.

AIM: Since controversial results have been obtained in studies dealing with nanoceria usefulness in biomedical applications, the transforming effects of long-term exposure to nanoceria in lung epithelial cells, alone or together with cigarette smoke condensate (CSC), were evaluated. MATERIALS & METHODS: In vitro cell transformation techniques were used to study several hallmarks of carcinogenesis. Morphology, cell proliferation, gene expression, cell migration, anchorage-independent cell growth and cell secretome were analyzed. RESULTS & CONCLUSION: Data evidence no transforming ability of nanoceria, but support a synergistic role on CSC's transforming ability. A more noticeable spindle-like phenotype, increased proliferation rate, higher degree of differentiation status dysregulation, higher migration capacity, increased anchorage-independent cell growth and higher levels of MMP-9 and cell growth promoting capability, were observed. In addition, nanoceria co-exposure exacerbates the expression of FRA-1.

Anti-inflammatory and antioxidant effect of cerium dioxide nanoparticles immobilized on the surface of silica nanoparticles in rat experimental pneumonia.

A massage with the potent counter-inflammatory material, cerium dioxide nanoparticles, is promising and the antioxidant properties of CeO2 are considered the main, if not the only, mechanism of this action. Nevertheless, the elimination of ceria nano-particles from the organism is very slow and there is a strong concern for toxic effect of ceria due to its accumulation. To overcome this problem, we engineered a combined material in which cerium nanoparticles were immobilized on the surface of silica nanoparticles (CeO2 NP), which is shown to be easily removed from an organism and could be used as carriers for nano-ceria. In our study particle size was 220±5nm, Zeta-potential -4.5mV (in water), surface charge density -17.22µC/cm2 (at pH 7). Thirty-six male Wistar rats, 5 months old and 250-290g were divided into four groups: 1) control; 2) CeO2 NP treatment; 3) experimental pneumonia (i/p LPS injection, 1mg/kg); and 4) experimental pneumonia treated with CeO2 NP (4 times during the study in dosage of 0.6mg/kg with an orogastric catheter). Gas exchange and pulmonary ventilation were measured four times: 0, 1, 3 and 24h after LPS injection in both untreated and CeO2 NP-treated animals. The mRNA of TNF-α, Il-6, and CxCL2 were determined by RT-PCR. ROS-generation in blood plasma and lung tissue homogenates were measured by means of lucigenin- and luminol-enhanced chemiluminescence. Endotoxemia in the acute phase was associated with: (1) pathological changes in lung morphology; (2) increase of ROS generation; (3) enhanced expression of CxCL2; and (4) a gradual decrease of VO2 and VE. CeO2 NP treatment of intact animals did not make any changes in all studied parameters except for a significant augmentation of VO2 and VE. CeO2 NP treatment of rats with pneumonia created positive changes in diminishing lung tissue injury, decreasing ROS generation in blood and lung tissue and decreasing pro-inflammatory cytokine expression (TNF-α, Il-6 and CxCL2). Oxygen consumption in this group was increased compared to the LPS pneumonia group. In our study we have shown anti-inflammatory and antioxidant effects of CeO2 NP. In addition, this paper is the first to report that CeO2 NP stimulates oxygen consumption in both healthy rats, and rats with pneumonia. We propose the key in understanding the mechanisms behind the phenomena lies in the property of CeO2 NP to scavenge ROS and the influence of this potent antioxidant on mitochondrial function. The study of biodistribution and elimination of СеО2NP is the purpose of our ongoing study.

The impact of cerium oxide nanoparticles on the salt stress responses of Brassica napus L.

Dwindling high quality water resources and growing population are forcing growers to irrigate crops with water of high salinity. It is well recognized that salinity negatively affects plant physiology and biochemistry, and represents one of the most serious threats to crop production and food security. Meanwhile, engineered nanoparticles (ENPs) are increasingly detected in irrigation water and agricultural soils due to the rapid advancement of nanotechnology. Previous research has demonstrated that ENPs such as cerium oxide nanoparticles (CeO2-NPs) exert significant impact on plant growth and production. However, almost all previous studies were conducted in well controlled environment. Knowledge on how ENPs affect plant development in a stressed condition is almost empty. The goal of the present study was to understand the physiological and biochemical changes in Brassica napus L. (canola) cv. 'Dwarf Essex' under synergistic salt stress and CeO2-NPs effects. Two salinity levels: 0 (control) and 100 mM NaCl, and three CeO2-NPs concentrations: 0 (control), 200 and 1000 mg kg-1 dry sand and clay mixture, were employed. As expected, 100 mM of NaCl significantly hindered plant growth and negatively affected the physiological processes of canola. Plants treated with CeO2-NPs had higher plant biomass, exhibited higher efficiency of the photosynthetic apparatus and less stress in both fresh water and saline water irrigation conditions Overall, our results demonstrated that CeO2-NPs led to changes in canola growth and physiology which improved the plant salt stress response but did not completely alleviate the salt stress of canola.

Soil organic matter influences cerium translocation and physiological processes in kidney bean plants exposed to cerium oxide nanoparticles.

Soil organic matter plays a major role in determining the fate of the engineered nanomaterials (ENMs) in the soil matrix and effects on the residing plants. In this study, kidney bean plants were grown in soils varying in organic matter content and amended with 0-500mg/kg cerium oxide nanoparticles (nano-CeO2) under greenhouse condition. After 52days of exposure, cerium accumulation in tissues, plant growth and physiological parameters including photosynthetic pigments (chlorophylls and carotenoids), net photosynthesis rate, transpiration rate, and stomatal conductance were recorded. Additionally, catalase and ascorbate peroxidase activities were measured to evaluate oxidative stress in the tissues. The translocation factor of cerium in the nano-CeO2 exposed plants grown in organic matter enriched soil (OMES) was twice as the plants grown in low organic matter soil (LOMS). Although the leaf cover area increased by 65-111% with increasing nano-CeO2 concentration in LOMS, the effect on the physiological processes were inconsequential. In OMES leaves, exposure to 62.5-250mg/kg nano-CeO2 led to an enhancement in the transpiration rate and stomatal conductance, but to a simultaneous decrease in carotenoid contents by 25-28%. Chlorophyll a in the OMES leaves also decreased by 27 and 18% on exposure to 125 and 250mg/kg nano-CeO2. In addition, catalase activity increased in LOMS stems, and ascorbate peroxidase increased in OMES leaves of nano-CeO2 exposed plants, with respect to control. Thus, this study provides clear evidence that the properties of the complex soil matrix play decisive roles in determining the fate, bioavailability, and biological transport of ENMs in the environment.

Foliar applied nanoscale and microscale CeO2 and CuO alter cucumber (Cucumis sativus) fruit quality.

There is lack of information about the effects of foliar applied nanoparticles on fruit quality. In this study, three week-old soil grown cucumber seedlings were foliar-exposed to nCeO2, nCuO, and corresponding bulk counterparts at 50, 100, and 200mg/L. Respective suspensions/solutions were sprayed to experimental units in a volume of 250ml. Net photosynthesis rate (Pn), stomatal conductance (Gs), and transpiration rate (E) were measured 15days after treatment application and in 74day-old plants. Yield, fruit characteristics (size, weight, and firmness), Ce, Cu, and nutritional elements were also measured. Results showed a nano-specific decrement on Pn (22% and 30%) and E (11% and 17%) in seedling leaves exposed to nCeO2 and nCuO at 200mg/L, respectively, compared with control. nCeO2 at 50mg/L, bCeO2 at 200mg/L, and all Cu treatments, except nCuO at 100mg/L, significantly reduced fruit firmness (p≤0.05), compared with control. However, nCuO at 200mg/L and bCuO at 50mg/L significantly increased fruit fresh weight (p≤0.05). At 200mg/L, nCeO2 and bCeO2 reduced fruit Zn by 25%, while nCuO and bCuO reduced fruit Mo by 51% and 44%, respectively, compared with control. This study has shown that when the route of exposure is the foliage, differences in particle size are less significant, compared to root-based exposure. To the authors' knowledge, this is the first report on the effect of foliar application of nCeO2 and nCuO upon yield and nutritional quality of cucumber.

Hard and soft tissue responses to three different implant materials in a dog model.

The aim of this study was to assess hard and soft tissue responses using three dental implants made of different materials. Implants made of titanium (Ti), yttria-stabilized tetragonal zirconia polycrystals (Y-TZP) and ceria partially stabilized zirconia/alumina nanocomposite (Ce-TZP/Al2O3) were used in a dog model. Five male beagles were sacrificed at three months after implantation, and harvested mandible were observed and analyzed. Histological observations were similar in all groups. There were no significant differences in any histomorphometric parameters. Our results suggested the possibility of Ce-TZP/Al2O3 as a dental implant material, similar to Ti and Y-TZP.

Redox-active cerium oxide nanoparticles protect human dermal fibroblasts from PQ-induced damage.

Recently, it has been published that cerium (Ce) oxide nanoparticles (CNP; nanoceria) are able to downregulate tumor invasion in cancer cell lines. Redox-active CNP exhibit both selective pro-oxidative and antioxidative properties, the first being responsible for impairment of tumor growth and invasion. A non-toxic and even protective effect of CNP in human dermal fibroblasts (HDF) has already been observed. However, the effect on important parameters such as cell death, proliferation and redox state of the cells needs further clarification. Here, we present that nanoceria prevent HDF from reactive oxygen species (ROS)-induced cell death and stimulate proliferation due to the antioxidative property of these particles.

Pulmonary toxicity of nanomaterials: a critical comparison of published in vitro assays and in vivo inhalation or instillation studies.

To date, guidance on how to incorporate in vitro assays into integrated approaches for testing and assessment of nanomaterials is unavailable. In addressing this shortage, this review compares data from in vitro studies to results from in vivo inhalation or intratracheal instillation studies. Globular nanomaterials (ion-shedding silver and zinc oxide, poorly soluble titanium dioxide and cerium dioxide, and partly soluble amorphous silicon dioxide) and nanomaterials with higher aspect ratios (multiwalled carbon nanotubes) were assessed focusing on the Organisation for Economic Co-Operation and Development (OECD) reference nanomaterials for these substances. If in vitro assays are performed with dosages that reflect effective in vivo dosages, the mechanisms of nanomaterial toxicity can be assessed. In early tiers of integrated approaches for testing and assessment, knowledge on mechanisms of toxicity serves to group nanomaterials thereby reducing the need for animal testing.

Cerium oxide nanoparticles induced toxicity in human lung cells: role of ROS mediated DNA damage and apoptosis.

Cerium oxide nanoparticles (CeO2 NPs) have promising industrial and biomedical applications. In spite of their applications, the toxicity of these NPs in biological/physiological environment is a major concern. Present study aimed to understand the molecular mechanism underlying the toxicity of CeO2 NPs on lung adenocarcinoma (A549) cells. After internalization, CeO2 NPs caused significant cytotoxicity and morphological changes in A549 cells. Further, the cell death was found to be apoptotic as shown by loss in mitochondrial membrane potential and increase in annexin-V positive cells and confirmed by immunoblot analysis of BAX, BCl-2, Cyt C, AIF, caspase-3, and caspase-9. A significant increase in oxidative DNA damage was found which was confirmed by phosphorylation of p53 gene and presence of cleaved poly ADP ribose polymerase (PARP). This damage could be attributed to increased production of reactive oxygen species (ROS) with concomitant decrease in antioxidant "glutathione (GSH)" level. DNA damage and cell death were attenuated by the application of ROS and apoptosis inhibitors N-acetyl-L-cysteine (NAC) and Z-DEVD-fmk, respectively. Our study concludes that ROS mediated DNA damage and cell cycle arrest play a major role in CeO2 NPs induced apoptotic cell death in A549 cells. Apart from beneficial applications, these NPs also impart potential harmful effects which should be properly evaluated prior to their use.