Ceria nanoparticles: biomedical applications and toxicity. / 二氧化铈纳米颗粒：生物医学应用和毒性.

Ceria nanoparticles (CeO2 NPs) have become popular materials in biomedical and industrial fields due to their potential applications in anti-oxidation, cancer therapy, photocatalytic degradation of pollutants, sensors, etc. Many methods, including gas phase, solid phase, liquid phase, and the newly proposed green synthesis method, have been reported for the synthesis of CeO2 NPs. Due to the wide application of CeO2 NPs, concerns about their adverse impacts on human health have been raised. This review covers recent studies on the biomedical applications of CeO2 NPs, including their use in the treatment of various diseases (e.|g., Alzheimer's disease, ischemic stroke, retinal damage, chronic inflammation, and cancer). CeO2 NP toxicity is discussed in terms of the different systems of the human body (e.|g., cytotoxicity, genotoxicity, respiratory toxicity, neurotoxicity, and hepatotoxicity). This comprehensive review covers both fundamental discoveries and exploratory progress in CeO2 NP research that may lead to practical developments in the future.

Nano-CeO2 activates physical and chemical defenses of garlic (Allium sativum L.) for reducing antibiotic resistance genes in plant endosphere.

The transmission of manure- and wastewater-borne antibiotic-resistant bacteria (ARB) to plants contributes to the proliferation of antimicrobial resistance in agriculture, necessitating effective strategies for preventing the spread of antibiotic resistance genes (ARGs) from ARB in the environment to humans. Nanomaterials are potential candidates for efficiently controlling the dissemination of ARGs. The present study investigated the abundance of ARGs in hydroponically grown garlic (Allium sativum L.) following nano-CeO2 (nCeO2) application. Specifically, root exposure to nCeO2 (1, 2.5, 5, 10 mg L-1, 18 days) reduced ARG abundance in the endosphere of bulbs and leaves. The accumulation of ARGs (cat, tet, and aph(3')-Ia) in garlic bulbs decreased by 24.2-32.5 % after nCeO2 exposure at 10 mg L-1. Notably, the lignification extent of garlic stem-disc was enhanced by 10 mg L-1 nCeO2, thereby accelerating the formation of an apoplastic barrier to impede the upward transfer of ARG-harboring bacteria to garlic bulbs. Besides, nCeO2 upregulated the gene expression related to alliin biosynthesis and increased allicin content by 15.9-16.2 %, promoting a potent antimicrobial defense for reducing ARG-harboring bacteria. The potential exposure risks associated with ARGs and Ce were evaluated according to the estimated daily intake (EDI). The EDI of ARGs exhibited a decrease exceeding 95 %, while the EDI of Ce remained below the estimated oral reference dose. Consequently, through stimulating physical and chemical defenses, nCeO2 contributed to a reduced EDI of ARGs and Ce, highlighting its potential for controlling ARGs in plant endosphere within the framework of nano-enabled agrotechnology.

Safety assessment and gastrointestinal retention of orally administered cerium oxide nanoparticles in rats.

Cerium oxide nanoparticles (CeO2 NPs, NM-212) are well-known for their catalytic properties and antioxidant potential, and have many applications in various industries, drug delivery, and cosmetic formulations. CeO2 NPs exhibit strong antimicrobial activity and can be used to efficiently remove pathogens from different environments. However, knowledge of the toxicological evaluation of CeO2 NPs is too limited to support their safe use. In this study, CeO2 NPs were orally administered to Sprague Dawley rats for 13 weeks at the doses of 0, 10, 100, and 1000 mg/kg bw/day, followed by a four week recovery period. The hematology values for the absolute and relative reticulocyte counts in male rats treated with 1000 mg/kg bw/day CeO2 NPs were lower than those in control rats. The clinical chemistry values for sodium and chloride in the treated male rat groups (100 and 1000 mg/kg/day) and total protein and calcium in the treated female rat groups (100 mg/kg/day) were higher than those in the control groups. However, these changes were not consistent in both sexes, and no abnormalities were found in the corresponding pathological findings. The results showed no adverse effects on any of the parameters assessed. CeO2 NPs accumulated in the jejunum, colon, and stomach wall of rats administered 1000 mg/kg CeO2 NPs for 90 days. However, these changes were not abnormal in the corresponding histopathological and immunohistochemical examinations. Therefore, 1000 mg/kg bw/day may be considered the "no observed adverse effect level" of CeO2 NPs (NM-212) in male and female SD rats under the present experimental conditions.

The cerium oxide nanoparticles toxicity induced physiological, histological and biochemical alterations in freshwater mussels, Unio crassus.

INTRODUCTION: Releasing of cerium oxide nanoparticles (nano-CeO2) to the nature has increased due to the widespread use in many fields ranging from cosmetics to the food industry. Therefore, nano-CeO2 has been included in the Organization for Economic Co-operation and Development's (OECD) priority list for engineering nanomaterials. In this study, the effects of nano-CeO2 on the freshwater mussels were investigated to reveal the impact on the freshwater systems on model organism. METHODS: First, the chemical and structural properties of nano-CeO2 were characterized in details. Second, the freshwater mussels were exposed to environmentally relevant concentrations of nano-CeO2 as 10 mg, 25 mg and 50 mg/L during 48-h and 7-d. Third, after the exposure periods, hemolymph and tissue samples were taken to analyse the Total Hemocyte Counts (THCs) histology and oxidative stress parameters (total antioxidant status, glutathione, glutathione-S-transferase, and advanced oxidative protein products). RESULTS: Significant decrease of the THCs was observed in the nano-CeO2 exposed mussels compared to the control group (P < 0.05). The histological results showed a positive association between nano-CeO2 exposure concentration in the water and level of tissue damage and histopathological alterations were detected in the gill and the digestive gland tissues. Oxidative stress parameters were slightly affected after exposure to nano-CeO2 (P > 0.05). In conclusion, this study showed that acute exposure of freshwater mussels to nano-CeO2 did not pose significant biological risk. However, it has been proven that mussels are able to accumulate nano-CeO2 significantly in their bodies. CONCLUSION: This suggests that nano-CeO2 may be a potential risk to other organisms in the ecosystem through trophic transfer in the food-web based on their habitat and niche in the ecosystem.

Toxicokinetics of praseodymium and cerium administered as chloride salts in Sprague-Dawley rats: impacts of the dose and of co-exposure with additional rare earth elements.

We conducted a rat exposure study to assess the impacts of dose and co-exposure with other rare earth elements (REEs) on the toxicokinetics of praseodymium (Pr) and cerium (Ce). We first determined the kinetic profiles of elemental Pr and Ce in blood, urine and feces along with tissue levels at sacrifice on the seventh day following intravenous injection of PrCl3 or CeCl3 at 0.3 or 1 mg/kg bw (of the chloride salts) in adult male Sprague-Dawley rats (n = 5 per group). In blood, Pr and Ce half-lives for the initial phase (t1/2α) increased with increasing doses, while their half-lives for the terminal phase (t1/2ß) were similar at both doses. In urine, a minor excretion route, no significant effect of the dose on the cumulative excretion was apparent. In feces, a major excretion route, the fraction of the Pr dose recovered was significantly lower at the 1 mg/kg bw dose compared to the 0.3 mg/kg bw dose, while no significant dose effect was apparent for Ce. In the liver and spleen, which are the main sites of REEs accumulation, there was a significant effect of the dose only for Ce retention in the spleen (i.e., increased retention of Ce in spleen at higher dose). Results were compared with those of a previous toxicokinetic study with a similar design but an exposure to a quaternary mixture of CeCl3, PrCl3, NdCl3 and YCl3, each administered at 0.3 mg/kg bw or 1 mg/kg bw. A mixture effect was apparent for the initial elimination phase (t1/2α) of Pr and Ce from blood and for the fecal excretion of Ce at the 1 mg/kg bw. In urine and liver, there was no evident overall mixture effect; in the spleen, there was a higher retention of Pr and Ce in rats exposed to the mixture at the 0.3 mg/kg bw, but not at the 1 mg/kg bw dose. Overall, this study showed that the dose and mixture exposure are two important factors to consider as determinants of the toxicokinetics of REEs.

The effect of gibberellic acid on wheat growth and nutrient uptake under combined stress of cerium, zinc and titanium dioxide nanoparticles.

Nanoparticles (NPs) are released and dispersed in the environment because of increased manufacturing and use of nano products. NPs disturb the growth of plants depending upon types, exposure duration and plant species. The purpose of this research was to explore the role of gibberellic acid (GA) exposure through foliar route on wheat growth under alone or combined soil application of cerium oxide (CeO2), zinc oxide (ZnO), and titanium dioxide (TiO2) NPs. GA was foliar-applied (200 mg/L) on the wheat plants treated with individual and in all possible combination of the selected NPs. Explorations have revealed that the combination of NPs and GA worked well to enhance the plant growth and selected nutrient status than NPs alone. Furthermore, GA decreased the boosted antioxidant enzyme activities under the combination and individual NPs compared to the alone NPs treated plants, lowered the oxidative stress in wheat plants which provided the additional proof that GA decreased oxidative damage in plants. Combined NPs showed differential effects than individual NPs application irrespective of GA exposure which varied with NPs combination and studied parameters of plants. GA + NPs differentially affected the potassium, phosphorus, iron and manganese concentrations in wheat tissues than NPs alone treatments. Overall, GA can be applied when there is excess of NPs (either alone or in combination) in the growth medium to ensure the growth of crops. However, further studied are needed with other plant species and alone or combined use of different NPs under GA treatment before any final recommendation.

Combined cerium and zinc oxide nanoparticles induced hepato-renal damage in rats through oxidative stress mediated inflammation.

The toxicity profiles of nanoparticles (NPs) used in appliances nowadays remains unknown. In this study, we investigated the toxicological consequences of exposure to cerium oxide (CeO2) and zinc oxide (ZnO) nanoparticles given singly or in combination on the integrity of liver and kidney of male Wistar rats. Twenty (20) rats were allotted into four groups and treated as: Control (normal saline), CeO2NPs (50 µg/kg), ZnONPs (80 µg/kg) and [CeO2NPs (50 µg/kg) + ZnONPs (80 µg/kg)]. The nanoparticles were given to the animals through the intraperitoneal route, three times per week for four repeated weeks. Results revealed that CeO2 and ZnO NPs (singly) increased serum AST and ALT by 29% & 57%; 41% & 18%, and co-administration by 53% and 23%, respectively. CeO2 and ZnO NPs increased hepatic and renal malondialdehyde (MDA) by 33% and 30%; 38% and 67%, respectively, while co-administration increased hepatic and renal MDA by 43% and 40%, respectively. The combined NPs increased hepatic NO by 28%. Also, CeO2 and ZnO NPs, and combined increased BAX, interleukin-1ß and TNF-α by 45, 38, 52%; 47, 23, 82% and 41, 83, 70%, respectively. Histology revealed hepatic necrosis and renal haemorrhagic parenchymal in NPs-treated rats. Summarily, CeO2 and ZnO NPs produced oxidative injury and induced inflammatory process in the liver and kidney of experimental animals.

Benzo(a)pyrene and Cerium Dioxide Nanoparticles in Co-Exposure Impair Human Trophoblast Cell Stress Signaling.

Human placenta is a multifunctional interface between maternal and fetal blood. Studying the impact of pollutants on this organ is crucial because many xenobiotics in maternal blood can accumulate in placental cells or pass into the fetal circulation. Benzo(a)pyrene (BaP) and cerium dioxide nanoparticles (CeO2 NP), which share the same emission sources, are found in ambient air pollution and also in maternal blood. The aim of the study was to depict the main signaling pathways modulated after exposure to BaP or CeO2 NP vs. co-exposure on both chorionic villi explants and villous cytotrophoblasts isolated from human term placenta. At nontoxic doses of pollutants, BaP is bioactivated by AhR xenobiotic metabolizing enzymes, leading to DNA damage with an increase in γ-H2AX, the stabilization of stress transcription factor p53, and the induction of its target p21. These effects are reproduced in co-exposure with CeO2 NP, except for the increase in γ-H2AX, which suggests a modulation of the genotoxic effect of BaP by CeO2 NP. Moreover, CeO2 NP in individual and co-exposure lead to a decrease in Prx-SO3, suggesting an antioxidant effect. This study is the first to identify the signaling pathways modulated after co-exposure to these two pollutants, which are common in the environment.

Hormetic Effects of Cerium, Lanthanum and Their Combination at Sub-micromolar Concentrations in Sea Urchin Sperm.

Rare earth elements (REEs) cerium (Ce) and lanthanum (La) and their combination were tested across a concentration range, from toxic (10-4 to 10-5 M) to lower concentrations (10-6 to 10-8 M) for their effects on sea urchin (Sphaerechinus granularis) sperm. A significantly decreased fertilization rate (FR) was found for sperm exposed to 10-5 M Ce, La and their combination, opposed to a significant increase of FR following 10-7 and 10-8 M REE sperm exposure. The offspring of REE-exposed sperm showed significantly increased developmental defects following sperm exposure to 10-5 M REEs vs. untreated controls, while exposure to 10-7 and 10-8 M REEs resulted in significantly decreased rates of developmental defects. Both of observed effects-on sperm fertilization success and on offspring quality-were closely exerted by Ce or La or their combination.

Maternal cerium nitrate exposure induces developmental immunotoxicity in BALB/c mouse offspring.

With the increasing application of cerium and rare-earth elements (REEs), cerium exposure is becoming more widespread. However, there remains a paucity of evidence on developmental immunotoxicity of cerium. This study was designed to examine the developmental immunotoxicity of gestational and postnatal exposure to cerium nitrate (CN) in BALB/C mouse offspring. Dams were given CN by oral gavage at 0, 0.002, 0.02 and 0.2 mg/kg from gestation day 5 (GD5) to postnatal day 21 (PND 21). On PND 21, the highest dose of CN significantly suppressed the NK cell cytotoxicity, and reduced the proportions of NK cells in peripheral blood and spleen of both female and male pups, however, the proportions of monocytes in peripheral blood and macrophages in spleen only increased in female pups. For adaptive immunity, on PND 21, the suppression of T/B lymphocyte proliferation, humoral and cellular immune responses (number of splenic plaque-forming cells, PFC, and delayed-type hypersensitivity, DTH) were observed in both female and male pup mice exposed to 0.2 mg/kg CN. However, the fall of proportions of T/B lymphocytes in peripheral blood (PB), spleen and mesenteric lymph node (MLN) only found in female pups at 0.2 mg/kg on PND 21. Most indications recovered to normal after 3-week cessation of CN exposure, except the reduction of DTH and PFC. From the findings in this study, the lowest-observed-adverse-effect level (LOAEL) of CN for developmental immunotoxicity was estimated to be 0.2 mg/kg bw per day.

Selenium nanoparticles reduce Ce accumulation in grains and ameliorate yield attributes in mung bean (Vigna radiata) exposed to CeO2.

Exposure of crops to CeO2 nanoparticles (nCeO2) in agricultural environments impact crop quality and human health. In this regard, the effects of selenium nanoparticles (nSe) on the yield and quality of Vigna radiata (L.) exposed to nCeO2 were investigated. The experiment was carried out as a factorial with two factors: NPs (nCeO2, and nSe) as factor one and concentrations as factor two [(0, 250, 500 and 1000 mg/L nCeO2; 0, 25, 50 and 75 mg/L nSe)]. Nanoparticles were foliar applied to 45-day old mung bean shoot in two steps and one-week interval. At 250-1000 mg/L, nCeO2 increased P, protein and Ce accumulation in grain. Additionally, at 1000 mg/L, the nCeO2, significantly decreased seed number, yield, Fe, and Zn storage in seeds. Conversely, at 25 and 50 mg/L, nSe stimulated the growth and yield of mung bean, and significantly increased P, Fe, Zn, and Se in seeds, but reduced the protein content in seeds. The Se25+Ce250 and Se50+Ce250 significantly increased pod number, seed number, grain weight, yield, Fe, Zn and Se storage in grains. In contrast, the Ce accumulation in seeds decreased in all combination treatments (nCeO2 + nSe) compared to their respective single nCeO2 treatments. Moreover, in the plants exposed to high nCeO2 concentrations, nSe application resulted in undamaged vacuoles, less starch granules' accumulation, significant yield improvement, and elevated Fe, Se, and Zn in seeds. Data suggest that selenium nanoparticles prevent nCeO2 stress in mung bean and improve grain production and quality.

Uptake and toxicity of cerium dioxide nanoparticles with different aspect ratio.

Cerium dioxide nanoparticles (CeONPs) have been extensively applied in research for future energy development due to two common oxidation states on their surface. Considering that shape (aspect ratio) is a key determinant of NPs-induced toxicity, we compared the toxicity of hexagonal (H)- and rod-shaped (R)-CeONPs in mice. At 24 h after pharyngeal aspiration, both types of CeONPs recruited surrounding immune cells (monocytes and neutrophils) into the lung, and R-CeONPs induced a more severe pulmonary inflammatory response compared with H-CeONPs. To identify an indicator to predict pulmonary inflammatory responses at the cellular level, we also investigated their responses in alveolar macrophage cells. At 24 h after treatment, both types of CeONPs were mainly located within the vacuoles (partially, in the lysosome) in the cytoplasm. Mitochondrial damage, intracellular calcium accumulation, and increased NO production were observed in cells exposed to both types of CeONPs, ultimately resulting in a decrease in cell viability. More interestingly, both types of CeONPs formed multinucleated giant cells. Meanwhile, contrary to when suspended in deionized water, R-CeONPs were strongly aggregated with a negative charge in cell culture media, whereas H-CeONPs were relatively well-dispersed with a positive charge. R-CeONPs-induced lysosomal extension was also recovered by premix with negatively charged DNA, and even NPs suspended in cell culture media without cells were detected under the FACS system, suggesting interference by protein corona. Therefore, we suggest that shape (aspect ratio) is an important factor determining inhaled NPs-induced pathology and that the effect of the surface charge and protein corona should be carefully considered in interpreting results derived from in vitro tests. Furthermore, we propose that the relationship between the formation of multinucleated giant cells and the inflammatory response of inhaled CeONPs should be further studied.

Divergent responses and ecological risks of wheat (Triticum aestivum L.) to cerium oxide nanoparticles in different soil types.

Cerium oxide nanoparticles (nCeO2), as a common component for sustainable agriculture, have been broadly investigated due to their potential threat to the soil biodiversity and health. However, few studies considered the impacts of soil types on response of ecotoxicity of nCeO2 to plants. This study aimed to explore the effects of soil properties on ecological response of nCeO2 to wheat (Triticum aestivum L.) and assess the ecological risks of nCeO2 (0-1000 mg/kg) in red soil, yellow-brown soil, and brown soil by applying a multi-biomarker approach. The results showed that the clay content had the extremely significant correlation with acid solute fraction Ce in soil. Ce accumulation in wheat largely depended on acid-soluble fraction Ce, but not the total Ce. Both urease and invertase activities were highest in brown soil among the three soils, after exposure to diverse concentration nCeO2. Although wheat has a stronger antioxidant capacity in red soil, integrated biomarker response index proved that nCeO2 showed least toxicity to wheat in brown soil (IBRv2 = 34.3) among the three soils. These results indicated that the toxicity level of nCeO2 to wheat was not only related to contaminated concentration, but also greatly depended on soil properties. The soil types are important factors governing ecological risk of nCeO2 in soil, which needs to be adequately assessed and properly controlled.

Mechanisms of cerium-induced stress in plants: A meta-analysis.

A comprehensive evaluation of the effects of cerium on plants is lacking even though cerium is extensively applied to the environment. Here, the effects of cerium on plants were meta-analyzed using a newly developed database consisting of approximately 8500 entries of published data. Cerium affects plants by acting as oxidative stressor causing hormesis, with positive effects at low concentrations and adverse effects at high doses. Production of reactive oxygen species and its linked induction of antioxidant enzymes (e.g. catalase and superoxide dismutase) and non-enzymatic antioxidants (e.g. glutathione) are major mechanisms driving plant response mechanisms. Cerium also affects redox signaling, as indicated by altered GSH/GSSG redox pair, and electrolyte leakage, Ca2+, K+, and K+/Na+, indicating an important role of K+ and Na+ homeostasis in cerium-induced stress and altered mineral (ion) balance. The responses of the plants to cerium are further extended to photosynthesis rate (A), stomatal conductance (gs), photosynthetic efficiency of PSII, electron transport rate, and quantum yield of PSII. However, photosynthesis response is regulated not only by physiological controls (e.g. gs), but also by biochemical controls, such as via changed Hill reaction and RuBisCO carboxylation. Cerium concentrations <0.1-25 mg L-1 commonly enhance chlorophyll a and b, gs, A, and plant biomass, whereas concentrations >50 mg L-1 suppress such fitness-critical traits at trait-specific concentrations. There was no evidence that cerium enhances yields. Observations were lacking for yield response to low concentrations of cerium, whereas concentrations >50 mg Kg-1 suppress yields, in line with the response of chlorophyll a and b. Cerium affects the uptake and tissue concentrations of several micro- and macro-nutrients, including heavy metals. This study enlightens the understanding of some mechanisms underlying plant responses to cerium and provides critical information that can pave the way to reducing the cerium load in the environment and its associated ecological and human health risks.

Genotoxic hazard assessment of cerium oxide and magnesium oxide nanoparticles in Drosophila.

The use of metal oxide nanoparticles (NPs) is steadily spreading, leading to increased environmental exposures to many organisms, including humans. To improve our knowledge of this potential hazard, we have evaluated the genotoxic risk of cerium oxide (CeO2NPs) and magnesium oxide (MgONPs) nanoparticle exposures using Drosophila as an in vivo assay model. In this study, two well-known assays, such as the wing somatic mutation and recombination test (wing-spot assay) and the single-cell gel electrophoresis test (comet assay) were used. As a novelty, and for the first time, changes in the expression levels of a wide panel of DNA repair genes were also evaluated. Our results indicate that none of the concentrations of CeO2NPs increased the total spot frequency in the wing-spot assay, while induction was observed at the highest dose of MgONPs. Regarding the comet assay, both tested NPs were unable to induce single DNA strand breaks or oxidative damage in DNA bases. Nevertheless, exposure to CeO2NPs induced significant increases in the expression levels of the Mlh1 and Brca2 genes, which are involved in the double-strand break repair pathway, together with a decrease in the expression levels of the MCPH1 and Rad51D genes. Regarding the effects of MgONPs exposure, the expression levels of the Ercc1, Brca2, Rad1, mu2, and stg genes were significantly increased, while Mlh1 and MCPH1 genes were decreased. Our results show the usefulness of our approach in detecting mild genotoxic effects by evaluating changes in the expression of a panel of genes involved in DNA repair pathways.

Comparison of biodistribution of cerium oxide nanoparticles after repeated oral administration by gavage or snack in Sprague Dawley rats.

The rate of translocation of ingested nanoparticles (NPs) and how the uptake is affected by a food matrix are key aspects of health risk assessment. In this study, female Sprague Dawley rats (N = 4/group) received 0, 1.4, or 13 mg of cerium oxide (CeO2 NM-212) NPs/rat/day by gavage or in a chocolate spread snack 5 days/week for 1 or 2 weeks followed by 2 weeks of recovery. A dose and time-dependent uptake in the liver and spleen of 0.1-0.3 and 0.004-0.005 parts per million (ng/mg) of the total administered dose was found, respectively. There was no statistically significant difference in cerium concentration in the liver or spleen after gavage compared to snack dosing. Microscopy revealed indications of necrotic changes in the liver and decreased cellularity in white pulp in the spleen. The snack provided precise administration and a more human-relevant exposure of NPs and could improve animal welfare as alternative to gavage.

Genotoxic assessment of cerium and magnesium nanoparticles and their ionic forms in Eisenia hortensis coelomocytes by alkaline comet assay.

The present study aimed to evaluate the genotoxic potential of cerium oxide (CeO2 ), magnesium oxide (MgO) nanoparticles and their ionic forms by alkaline comet assay. Eisenia hortensis were exposed to different series of concentrations (25, 50, 100, 200, and 400 µg/ml) of chemicals for 48 h to find LC50 . The LC50 for MgO and CeO2 NPs were 70 and 80 µg/ml. Whereas, the LC50 for their ionic forms were 50 and 70 µg/ml. To assess the potential DNA damage caused by the chosen chemicals, E. hortensis was further exposed for 48 h to the following concentrations, based on their respective LC50s : LC50/2 , LC50 , and 2xLC50 . Comet scores demonstrated the significant increase (p < 0.05) in DNA damage at all concentrations, both for NPs and ionic forms in a concentration-dependent manner. Findings of the present study revealed the genotoxic effects of CeO2 NPs, MgO NPs and their ionic forms on E. hortensis. RESEARCH HIGHLIGHTS: Genotoxic assessment of CeO2 and MgO NPs and their ionic forms was conducted. Characterization of NPs through electron microscopy and alkaline comet assay was performed on E. Hortensis. Highest DNA damage of CeO2 and MgO NPs was observed on earthworm.

A comprehensive study of selenium and cerium oxide nanoparticles on mung bean: Individual and synergistic effect on photosynthesis pigments, antioxidants, and dry matter accumulation.

In this study, the interaction effects of CeO2 NPs (250, 500 and 1000 mg L-1) and Se NPs (25, 50 and 75 mg L-1) were evaluated in mung bean (Vigna radiata). Single NPs and their combinations were foliar applied to 45-day old mung bean plants under greenhouse conditions. In each pot, a total volume of 100 mL of NPs suspension was sprayed on the plants shoot in two steps and one-week interval. After 94 days of growth, membrane degradation, antioxidant activity, photosynthetic pigments, and dry matter accumulation were assessed. At 250 and 500 mg CeO2-NPs L-1, there was partial increase of dry matter, stimulated activity of antioxidant enzymes (p ≤ 0.05), and reactive oxygen species (ROS). However, at 1000 mg L-1, CeO2-NPs caused strong accumulation of ROS (p ≤ 0.05), enlargement of starch granules and swelling of chloroplasts. In addition, at such concentration, there was accumulation of starch granules, reduction of photosynthetic pigments, biological nitrogen fixation, chlorosis, and a significant retardation in plant growth, compared with control, (p ≤ 0.05). Combination of Se-NPs (25 and 50 mg L-1) with 250 mg L-1 of CeO2 NPs decreased hydrogen peroxide, improved CAT, Chla, Chlb, and increased dry matter (p ≤ 0.05). At 1000 mg CeO2 NPs L-1, foliar spray of Se-NPs led to Ce accumulation in the cell wall and increased levels of SOD and proline (p ≤ 0.05). Results showed that 25 and 50 mg Se NPs L-1 ameliorate the stress of CeO2 NPs by upregulating photosynthesis pigments, antioxidants, and dry matter accumulation. Therefore, depending on the CeO2 NPs concentration, the mechanisms of Se NPs in modulating CeO2 NPs stress varied; low concentrations of Se NPs may strengthen the metabolism of legumes, and protect them against foliar toxicity of CeO2 NPs in semi-arid ecosystems.

In Vitro Hepatotoxic and Neurotoxic Effects of Titanium and Cerium Dioxide Nanoparticles, Arsenic and Mercury Co-Exposure.

Considering the increasing emergence of new contaminants, such as nanomaterials, mixing with legacy contaminants, including metal(loid)s, it becomes imperative to understand the toxic profile resulting from these interactions. This work aimed at assessing and comparing the individual and combined hepatotoxic and neurotoxic potential of titanium dioxide nanoparticles (TiO2NPs 0.75-75 mg/L), cerium oxide nanoparticles (CeO2NPs 0.075-10 µg/L), arsenic (As 0.01-2.5 mg/L), and mercury (Hg 0.5-100 mg/L) on human hepatoma (HepG2) and neuroblastoma (SH-SY5Y) cells. Viability was assessed through WST-1 (24 h) and clonogenic (7 days) assays and it was affected in a dose-, time- and cell-dependent manner. Higher concentrations caused greater toxicity, while prolonged exposure caused inhibition of cell proliferation, even at low concentrations, for both cell lines. Cell cycle progression, explored by flow cytometry 24 h post-exposure, revealed that TiO2NPs, As and Hg but not CeO2NPs, changed the profiles of SH-SY5Y and HepG2 cells in a dose-dependent manner, and that the cell cycle was, overall, more affected by exposure to mixtures. Exposure to binary mixtures revealed either potentiation or antagonistic effects depending on the composition, cell type and time of exposure. These findings prove that joint toxicity of contaminants cannot be disregarded and must be further explored.

Physiochemical responses of earthworms (Eisenia fetida) under exposure to lanthanum and cerium alone or in combination in artificial and contaminated soils.

Rare earth elements inevitably release into the soil due to their widespread application. However, it is unclear how they affect the soil animals. The study surveyed the growth and physiological responses of earthworm (Eisenia fetida) exposed into artificial soils spiked with La, Ce, and their mixture, and actual mine soil collected from an abandoned La-Ce mining area (Mianning, Sichuan). The results showed that the 1000-1200 mg/kg combined exposure in two soils induced significant histopathological and phenotypic changes of earthworms. Concentration significantly affected the superoxide dismutase (SOD), peroxidase (POD), malondialdehyde (MDA), and protein of E. fetida and the effects differentiated with the prolonging duration. These indicators were negatively affected under the La stress ≥800 mg/kg (SOD, POD, and protein), the 1200 mg/kg (SOD), Ce stress ≥1000 mg/kg (protein), and the combination ≥800 mg/kg (SOD, POD) and ≥1000 mg/kg (protein). Artificial combination had -15.04% (SOD), 8.87% (POD), 5.64% (MDA), and -8.34% (protein) difference compared with the contamination soil, respectively. Overall, E. fetida respond sensitively under the La and Ce stress, the antioxidant defense system and the lipid peroxidation were stimulated, and the artificial soil might overestimate eco-toxicological effect.