Bafi A1 inhibits nano-copper oxide-induced mitochondrial damage by reducing the release of copper from lysosomes.

This study demonstrated that both copper oxide nanoparticles (CuO-NPs) and copper nanoparticles (Cu-NPs) can cause swelling, inflammation, and cause damage to the mitochondria of alveolar type II epithelial cells in mice. Cellular examinations indicated that both CuO-NPs and Cu-NPs can reduce cell viability and harm the mitochondria of human bronchial epithelial cells, particularly Beas-2B cells. However, it is clear that CuO-NPs exhibit a more pronounced detrimental effect compared with Cu-NPs. Using bafilomycin A1 (Bafi A1), an inhibitor of lysosomal acidification, was found to enhance cell viability and alleviate mitochondrial damage caused by CuO-NPs. Additionally, Bafi A1 also reduces the accumulation of dihydrolipoamide S-acetyltransferase (DLAT), a marker for mitochondrial protein toxicity, induced by CuO-NPs. This observation suggests that the toxicity of CuO-NPs depends on the distribution of copper particles within cells, a process facilitated by the acidic environment of lysosomes. The release of copper ions is thought to be triggered by the acidic conditions within lysosomes, which aligns with the lysosomal Trojan horse mechanism. However, this association does not seem to be evident with Cu-NPs.

Synthesis of silver and copper nanoparticle using Spirulina platensis and evaluation of their anticancer activity.

The present research displays the green synthesis of stable silver nanoparticles (Ag-NPs) and copper oxide nanoparticles (CuO-NPs). The aqueous solution of Spirulina platensis (blue green algae) source was used as a reducing and capping agent and this study assessed the cytotoxicity of Ag- and CuO-NPs on three cancer cell cultures: A549 (lung cancer), HCT (human colon cancer), Hep2 (laryngeal carcinoma cancer) and normal cell (WISH). For NPs characterization, the UV/Vis spectroscopy was used where their formation and crystallinity were proven with λmax values for Ag- and CuO-NPs of 425 and 234 nm, respectively. According to X-ray diffraction and transmission electron microscopy (TEM), Ag-NPs were spherical in shape (size 2.23-14.68 nm) and CuO-NPs were small (size 3.75-12.4 nm). Zeta potential analysis showed the particles potential, which was recorded by -14.95 ± 4.31 mV for Ag-NPs and -21.63 ± 4.90 mV for CuO-NPs. After that, Ag- and CuO-NPs were assessed for anticancer properties against A549, HCT, Hep2 and WISH. IC50 of Ag-NPs recorded 15.67, 12.94, 3.8 and 10.44 µg/ml for WISH, A549, HCT and Hep2, respectively. IC50 for CuO-NPs was recorded as 32.64, 54.59, 3.98 and 20.56 µg/ml for WISH, A549, HCT and Hep2 cells, respectively. Safety limits for WISH and A549 were achieved 98.64% by 2.44 µg/ml and 83.43% by 4.88 µg/ml of Ag-NPs, and it was found to be 97.94% by 2.44 µg/ml against HCT, while that for Hep2 is 95.9% by 2.44 µg/ml. Concerning the anticancer effect of CuO-NPs, the safety limit was recorded as 88.70% by 2.44 and 98.48% by 4.88 µg/ml against WISH and A549, while HCT reached 89.92% by 2.44 µg/ml and Hep2 was 83.33% by 4.88 µg/ml. Green nanotechnology applications such as Ag-NPs and CuO-NPs have numerous benefits of ecofriendliness and compatibility for biomedical applications such as anticancer effects against cancer cells.

Benefit and potential risk: Effects of in ovo copper oxide nanoparticles supplementation on hatchability traits, organ weights and histological features of newly hatched chicks.

This investigation was directed to examine the influence of copper oxide nanoparticles (CuO-NPs) on the hatchability traits, and chick quality of newly hatched broiler chicks. A total of 480 eggs were randomly divided into four treatment groups, each consisting of three duplicates. As a negative control (NC), the first group was not injected; the second group was injected with saline and served as a positive control (PC), the third and fourth groups were injected with 30 and 60 ppm of (CuO-NPs)/egg. Eggs were injected into the amniotic fluid on the eighteenth day of the incubation period. Results showed that the hatchability, chick yield %, yolk free-body mass (YFBM), chick length, shank length (SL), and relative weight of the heart, gizzard and intestine of day-old broiler chicks were all unaffected by the in ovo injection of CuO-NPs. The Pasgar Score was slightly improved compared to the NC and PC groups. Also, the in ovo administration of CuO-NPs (60 ppm/egg) significantly increased the intestine length. Both levels of CuO-NPs significantly increased the concentration of Cu ions in the hepatic tissue. Additionally, different levels of tissue damage were seen in the liver of the birds that were given low or high dosages of CuO-NPs. Conclusively, the in ovo injection of CuO-NPs has a good result on the appearance of the chicks (Pasgar score). However, negative effect of CuO-NPs on liver tissue may raise concerns about the potential risks of applying CuO-NPs in ovo administration.

Bio-functionalized copper oxide/chitosan nanocomposite using Sida cordifolia and their efficient properties of antibacterial, anticancer activity against on breast and lung cancer cell lines.

Nanoparticles synthesis from green chemistry method is gaining a lot of attention due to their non-toxic, low cost and facile. In this study, a copper oxide nanoparticle (CuO NPs) was synthesized using Sida cordifolia aqueous leaf extract and incorporated chitosan biomolecules to potential enhancing of biological properties. The CuO NPs and chitosan (CS) embedded nanocomposite was noted as CuO-CS nanocomposite, its was physicochemical characterized by using of UV-Visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), X-ray Diffraction (XRD) and Field emission scanning electron microscopy (FE-SEM) with Energy dispersive X-ray (EDX) analysis. Bio-functionalized CuO-CS nanocomposite was performed antibacterial efficiency against both Gram positive (Staphylococcus aureus, Bacillus subtilis) and Gram negative (Salmonella typhi, Escherichia coli) bacteria through the Mueller Hinton agar (MHA) well diffusion techniques. The highest bactericidal activity was revealed Gram positive of B. subtilis and Gram negative of S. typhi bacteria, respectively. Further, the cytotoxicity effect of biosynthesized nanocomposite was an examined against human breast cancer MDA-MB-231 and lung cancer A549 cell lines. The half maximal inhibitory concentration is showed at 2 µg/mL for MDA-MB-231and 4 µg/mL was A549 cells. Live/dead cells were detected by fluorescence microscopic observation at the IC50 concentration. In furthermore, bio-functionalized CuO-CS nanocomposite was performed photocatatlytic dye degradation against for industrial dyes of crystal violet (CV) and malachite green (MG). From the results, synergic bio-functionalized CuO-CS nanocomposite was suggested potential suitable for biomedical applications as well as industrial wastewater treatment.

Synthesis, biomedical applications, and toxicity of CuO nanoparticles.

Versatile nature of copper oxide nanoparticles (CuO NPs) has made them an imperative nanomaterial being employed in nanomedicine. Various physical, chemical, and biological methodologies are in use for the preparation of CuO NPs. The physicochemical and biological properties of CuO NPs are primarily affected by their method of fabrication; therefore, selectivity of a synthetic technique is immensely important that makes these NPs appropriate for a specific biomedical application. The deliberate use of CuO NPs in biomedicine questions their biocompatible nature. For this reason, the present review has been designed to focus on the approaches employed for the synthesis of CuO NPs; their biomedical applications highlighting antimicrobial, anticancer, and antioxidant studies; and most importantly, the in vitro and in vivo toxicity associated with these NPs. This comprehensive overview of CuO NPs is unique and novel as it emphasizes on biomedical applications of CuO NPs along with its toxicological assessments which would be useful in providing core knowledge to researchers working in these domains for planning and conducting futuristic studies. KEY POINTS: • The recent methods for fabrication of CuO nanoparticles have been discussed with emphasis on green synthesis methods for different biomedical approaches. • Antibacterial, antioxidant, anticancer, antiparasitic, antidiabetic, and antiviral properties of CuO nanoparticles have been explained. • In vitro and in vivo toxicological studies of CuO nanoparticles exploited along with their respective mechanisms.

Effect of clay colloid - CuO nanoparticles interaction on retention of nanoparticles in different types of soils: role of clay fraction and environmental parameters.

The extensive application of metal oxide nanoparticles (NPs) in various sectors has raised concern about their subsequent release and potentially harmful impacts on the soil system. The present study has addressed the interaction of CuO NPs with bentonite clay colloids (CC) under varying environmental parameters as a model to represent the soil pore water scenario. Based on CuO - CC interaction in model and natural soil solution extracts (SSE), the role of clay fraction and their stability on CuO retention in various types of soils have been evaluated. Results suggested that increasing ionic strength (IS) in the system caused aggregation of CuO NPs, and in the presence of CC, critical coagulation concentration decreased drastically from 27.8 and 17.3 mM to 10.7 and 0.33 mM for NaCl and CaCl2 respectively, due to heteroaggregation in the system. Interestingly, in the SSE, the dominating role of ionic valency, dissolved organic carbon (DOC), and CC was observed in colloidal stabilization over IS. No significant impact of temperature was observed on the stability of CuO NPs both in model and SSE. Further, stability studies in the SSE were correlated with NPs retention behavior in soils. Observations suggest that retention of CuO NPs in soils is a function of binding of the colloidal fraction to the soil, which in turn depends on the colloidal stability. The highest retention was observed in black and laterite soils, whereas lower binding of clay fraction in red soil caused the least retention. A decrease in Kd values after a certain application concentration provided maximum sustainable application concentration of CuO NPs, which may vary with soil properties. Results suggest that the binding of clay and organic matter with a sandy matrix of soil plays a prime role in deciding the overall fate of CuO NPs in the soils.

Spirulina platensis mediated biosynthesis of Cuo Nps and photocatalytic degradation of toxic azo dye Congo red and kinetic studies.

The current research is designed to synthesis Copper oxide nanoparticles (CuO NPs) using Cyanobacterium in greener way. The NPs were synthesized using Spirulina platensis. The method is adopted for the less toxic, less cost and environment friendly method. The synthesized CuO NPs are capped and stabilized by the natural substance of S. platensis including flavonoids, phenolic and acid groups of the microorganism which was confirmed by the GC-MS analysis. Majorly, beta-ionone, p-cumic aldehyde, phytol compounds are identified by GC-MS and it may also involve in the preparation of NPs. Further, the characterization has been carried out using UV-Vis spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction, Scanning electron microscope (SEM), transmission electron microscope (TEM). All the analytical techniques are confirmed the formation of NPs. The formed NPs are showed significant peaks in XRD analysis which further compared with literature. Functional group analysis showed -OH group compounds in extract and it might involve in the formation of NPs. The photo catalytic activity of CuO NPs was showed significant photo degradation of Congo red (CR) dye. The consideration of intense peak, the size of CuO NPs was calculated and found to be 15.2 nm with spherical shape as resulted in morphological identification. The results are showed good photocatalytic activity, since the peak appeared at 230 and 495 nm corresponding to the benzene and azo group of Congo Red were gradually decreased with increase of time. The reaction was found to have nature of pseudo first order reaction. The rate constant was calculated and was found to be - k = 0.3459, which indicates the Congo red degradation was 0.3459 per minute. This study will be a base for budding researchers for their isolation of S. platensis active compounds and with the help of secondary metabolites (active compounds) CuO NPs were synthesized which further acted has degradation agent against Congo red.

New frontiers in the plant extract mediated biosynthesis of copper oxide (CuO) nanoparticles and their potential applications: A review.

Copper oxide nanoparticles (CuO NPs) are one of the most widely used nanomaterials nowadays. CuO NPs have numerous applications in biological processes, medicine, energy devices, environmental remediation, and industrial fields from nanotechnology. With the increasing concern about the energy crisis and the challenges of chemical and physical approaches for preparing metal NPs, attempts to develop modern alternative chemistry have gotten much attention. Biological approaches that do not produce toxic waste and therefore do not require purification processes have been the subject of numerous studies. Plants may be extremely useful in the study of biogenic metal NP synthesis. This review aims to shed more light on the interactions between plant extracts and CuO NP synthesis. The use of living plants for CuO NPs biosynthesis is a cost-effective and environmentally friendly process. To date, the findings have revealed many aspects of plant physiology and their relationships to the synthesis of NPs. The current state of the art and potential challenges in the green synthesis of CuO NPs are described in this paper. This study found a recent increase in the green synthesis of CuO NPs using various plant extracts. As a result, a thorough explanation of green synthesis and stabilizing agents for CuO NPs made from these green sources is given. Additionally, the multifunctional applications of CuO NPs synthesized with various plant extracts in environmental remediation, sensing, catalytic reduction, photocatalysis, diverse biological activities, energy storage, and several organic transformations such as reduction, coupling, and multicomponent reactions were carefully reviewed. We expect that this review could serve as a useful guide for readers with a general interest in the plant extract mediated biosynthesis of CuO NPs and their potential applications.

Time course of pulmonary inflammation and trace element biodistribution during and after sub-acute inhalation exposure to copper oxide nanoparticles in a murine model.

BACKGROUND: It has been shown that copper oxide nanoparticles (CuO NPs) induce pulmonary toxicity after acute or sub-acute inhalation exposures. However, little is known about the biodistribution and elimination kinetics of inhaled CuO NPs from the respiratory tract. The purposes of this study were to observe the kinetics of pulmonary inflammation during and after CuO NP sub-acute inhalation exposure and to investigate copper (Cu) biodistribution and clearance rate from the exposure site and homeostasis of selected trace elements in secondary organs of BALB/c mice. RESULTS: Sub-acute inhalation exposure to CuO NPs led to pulmonary inflammation represented by increases in lactate dehydrogenase, total cell counts, neutrophils, macrophages, inflammatory cytokines, iron levels in bronchoalveolar lavage (BAL) fluid, and lung weight changes. Dosimetry analysis in lung tissues and BAL fluid showed Cu concentration increased steadily during exposure and gradually declined after exposure. Cu elimination from the lung showed first-order kinetics with a half-life of 6.5 days. Total Cu levels were significantly increased in whole blood and heart indicating that inhaled Cu could be translocated into the bloodstream and heart tissue, and potentially have adverse effects on the kidneys and spleen as there were significant changes in the weights of these organs; increase in the kidneys and decrease in the spleen. Furthermore, concentrations of selenium in kidneys and iron in spleen were decreased, pointing to disruption of trace element homeostasis. CONCLUSIONS: Sub-acute inhalation exposure of CuO NPs induced pulmonary inflammation, which was correlated to Cu concentrations in the lungs and started to resolve once exposure ended. Dosimetry analysis showed that Cu in the lungs was translocated into the bloodstream and heart tissue. Secondary organs affected by CuO NPs exposure were kidneys and spleen as they showed the disruption of trace element homeostasis and organ weight changes.

CuO-NPs-triggered heterophil extracellular traps exacerbate liver injury in chicks by promoting oxidative stress and inflammatory responses.

With the widespread use of copper oxide nanoparticles (CuO-NPs), their potential toxicity to the environment and biological health has attracted close attention. Heterophil extracellular traps (HETs) are an innate immune mechanism of chicken heterophils against adverse stimuli, but excessive HETs cause damage. Here, we explored the effect and mechanism of CuO-NPs on HETs formation in vitro and further evaluated the potential role of HETs in chicken liver and kidney injury. Heterophils were exposed to 5, 10, and 20 µg/mL of CuO-NPs for 2 h. The results showed that CuO-NPs induced typical HETs formation, which was dependent on NADPH oxidase, P38 and extracellular regulated protein kinases (ERK1/2) pathways, and glycolysis. In in vivo experiments, fluorescence microplate and morphological analysis showed that CuO-NPs elevated the level of HETs in chicken serum and caused liver and kidney damage. Meanwhile, CuO-NPs caused hepatic oxidative stress (MDA, SOD, CAT, and GSH-PX imbalance), and also induced an increase in mRNA expression of their inflammatory and apoptosis-related factors (IL-1ß, IL-6, TNF-α, COX-2, iNOS, NLRP3, and Caspase-1, 3, 11). However, these results were significantly altered by DNase I (HETs degradation reagent). In conclusion, the present study demonstrates for the first time that CuO-NPs induce the formation of HETs and that HETs exacerbate pathological damage in chicken liver and kidney by promoting oxidative stress and inflammation, providing insights into immunotoxicity and potential prevention and treatment targets caused by CuO-NPs overexposure.

Phytoconstituents Assisted Biofabrication of Copper Oxide Nanoparticles and Their Antiplasmodial, and Antilarval Efficacy: A Novel Approach for the Control of Parasites.

The present work aimed to biofabricate copper oxide nanoparticles (CuO NPs) using Tinospora cordifolia leaf extract. The biofabricated CuO NPs were treated against the malarial parasite of chloroquine-resistant Plasmodium falciparum (INDO) and the antilarval efficacy was evaluated against the malaria vector Anopheles stephensi and dengue vector Aedes aegypti. The prominence at 285 nm in the UV-visible spectrum helped to identify the produced CuO NPs. Based on the XRD patterns, the concentric rings correspond to reflections at 38.26° (111), 44.11° (200), 64.58° (220), and 77.34° (311). These separations are indicative of CuO's face-centered cubic (fcc) structure. The synthesized CuO NPs have FTIR spectra with band intensities of 3427, 2925, 1629, 1387, 1096, and 600 cm-1. The absorbance band at 3427 cm-1 is known to be associated with the stretching O-H due to the alcoholic group. FTIR proved that the presence of the -OH group is responsible for reducing and capping agents in the synthesis of nanoparticles (NPs). The synthesized CuO NPs were found to be polymorphic (oval, elongated, and roughly spherical) in form with a size range of 11-47 nm and an average size of 16 nm when the morphology was examined using FESEM and HRTEM. The highest antiplasmodial efficacy against the chloroquine-resistant strain of P. falciparum (INDO) was found in the synthesized CuO NPs, with LC50 values of 19.82 µg/mL, whilst HEK293 cells are the least toxic, with a CC50 value of 265.85 µg/mL, leading to a selectivity index of 13.41. However, the antiplasmodial activity of T. cordifolia leaf extract (TCLE) and copper sulfate (CS) solution showed moderate activity, with LC50 values of 52.24 and 63.88 µg/mL, respectively. The green synthesized NPs demonstrated extremely high antilarval efficacy against the larvae of An. stephensi and Ae. aegypti, with LC50 values of 4.06 and 3.69 mg/L, respectively.

Dietary Antioxidant Curcumin Mitigates CuO Nanoparticle-Induced Cytotoxicity through the Oxidative Stress Pathway in Human Placental Cells.

The placenta is an important organ that maintains a healthy pregnancy by transporting nutrients to the fetus and removing waste from the fetus. It also acts as a barrier to protect the fetus from hazardous materials. Recent studies have indicated that nanoparticles (NPs) can cross the placental barrier and pose a health risk to the developing fetus. The high production and widespread application of copper oxide (CuO) NPs may lead to higher exposure to humans, raising concerns of health hazards, especially in vulnerable life stages, e.g., pregnancy. Oxidative stress plays a crucial role in the pathogenesis of adverse pregnancy outcomes. Due to its strong antioxidant activity, dietary curcumin can act as a therapeutic agent for adverse pregnancy. There is limited knowledge on the hazardous effects of CuO NPs during pregnancy and their mitigation by curcumin. This study aimed to investigate the preventive effect of curcumin against CuO NP-induced toxicity in human placental (BeWo) cells. CuO NPs were synthesized by a facile hydrothermal process and characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and photoluminescence techniques. We observed that curcumin did not induce toxicity in BeWo cells (1-100 µg/mL for 24 h), whereas CuO NPs decreased the cell viability dose-dependently (5-200 µg/mL for 24 h). Interestingly, CuO NP-induced cytotoxicity was effectively mitigated by curcumin co-exposure. The apoptosis data also exhibited that CuO NPs modulate the expression of several genes (p53, bax, bcl-2, casp3, and casp9), the activity of enzymes (caspase-3 and -9), and mitochondrial membrane potential loss, which was successfully reverted by co-treatment with curcumin. The mechanistic study suggested that CuO-induced reactive oxygen species generation, lipid peroxidation, and higher levels of hydrogen peroxide were significantly alleviated by curcumin co-exposure. Moreover, glutathione depletion and the lower activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and catalase) were effectively mitigated by curcumin. We believe this is the first report exhibiting that CuO-induced toxicity in BeWo cells can be effectively alleviated by curcumin. The pharmacological potential of dietary curcumin in NP-induced toxicity during pregnancy warrants further investigation.

Copper nanoparticles against benzimidazole-resistant Monilinia fructicola field isolates.

Nano-fungicides are expected to play an important role in future plant disease management. Their unique properties include a broad antimicrobial action, increased effectiveness in lower doses, slower a.i. release and/or enhanced drug delivery and an ability to control drug-resistant pathogens, which makes them appealing candidates for use as eco-friendly antifungal alternatives to counter fungicides resistance. Copper nanoparticles (Cu-NPs) could suppress mycelial growth in both sensitive (BENS) and resistant (BEN-R) Monilinia fructicola isolates harboring the E198A benzimidazole resistance mutation, more effectively than copper oxide NPs (CuO-NPs) and Cu(OH)2. A significant synergy of Cu-NPs with thiophanate methyl (TM) was observed against BEN-S isolates both in vitro and when applied on plum fruit suggesting enhanced availability or nanoparticle induced transformation of TM to carbendazim. ATP-dependent metabolism is probably involved in the mode of fungitoxic action of Cu-NPs as indicated by the synergy observed between Cu-NPs and the oxidative phosphorylation-uncoupler fluazinam (FM). Copper ion release contributed in the toxic action of Cu-NPs against M. fructicola, as indicated by synergism experiments with ethylenediaminetetraacetic acid (EDTA), although the lack of correlation between nano and bulk/ionic copper forms indicate an additional nano-property mediated mechanism of fungitoxic action. Results suggested that Cu-NPs can be effectively used in future plant disease management as eco-friendly antifungal alternatives to counter fungicides resistance and reduce the environmental footprint of synthetic fungicides.

Copper Oxide Nanoparticle-Based Immunosensor for Zearalenone Analysis by Combining Automated Sample Pre-Processing and High-Throughput Terminal Detection.

A rapid and high-throughput fluorescence detection method for zearalenone (ZEN) based on a CuO nanoparticle (NP)-assisted signal amplification immunosensor was developed using an automated sample pretreatment and signal conversion system. CuO NPs with high stability and biocompatibility were used as carriers to immobilize anti-ZEN antibodies. The obtained CuO NP-anti-ZEN can maintain the ability to recognize target toxins and act as both a signal source and carrier to achieve signal conversion using automated equipment. In this process, target toxin detection is indirectly transformed to Cu2+ detection because of the large number of Cu2+ ions released from CuO NPs under acidic conditions. Finally, a simple and high-throughput fluorescence assay based on a fluorescent tripeptide molecule was employed to detect Cu2+, using a multifunctional microporous plate detector. A good linear relationship was observed between the fluorescence signal and the logarithm of ZEN concentration in the range of 16.0-1600.0 µg/kg. Additionally, excellent accuracy with a high recovery yield of 99.2-104.9% was obtained, which was concordant with the results obtained from LC-MS/MS of naturally contaminated samples. The CuO NP-based assay is a powerful and efficient screening tool for ZEN detection and can easily be modified to detect other mycotoxins.

Dose-Dependent Physiological and Transcriptomic Responses of Lettuce (Lactuca sativa L.) to Copper Oxide Nanoparticles-Insights into the Phytotoxicity Mechanisms.

Understanding the complex mechanisms involved in plant response to nanoparticles (NPs) is indispensable in assessing the environmental impact of nano-pollutants. Plant leaves can directly intercept or absorb NPs deposited on their surface; however, the toxicity mechanisms of NPs to plant leaves are unclear. In this study, lettuce leaves were exposed to copper oxide nanoparticles (CuO-NPs, 0, 100, and 1000 mg/L) for 15 days, then physiological tests and transcriptomic analyses were conducted to evaluate the negative impacts of CuO-NPs. Both physiological and transcriptomic results demonstrated that CuO-NPs adversely affected plant growth, photosynthesis, and enhanced reactive oxygen species (ROS) accumulation and antioxidant system activity. The comparative transcriptome analysis showed that 2270 and 4264 genes were differentially expressed upon exposure to 100 and 1000 mg/L CuO-NPs. Gene expression analysis suggested the ATP-binding cassette (ABC) transporter family, heavy metal-associated isoprenylated plant proteins (HIPPs), endocytosis, and other metal ion binding proteins or channels play significant roles in CuO-NP accumulation by plant leaves. Furthermore, the variation in antioxidant enzyme transcript levels (POD1, MDAR4, APX2, FSDs), flavonoid content, cell wall structure and components, and hormone (auxin) could be essential in regulating CuO-NPs-induced stress. These findings could help understand the toxicity mechanisms of metal NPs on crops, especially NPs resulting from foliar exposure.

Effect of Soil Properties and Aging Time on Oral and Inhalation Bioaccessibility of Copper Oxide Nanoparticles in Soils.

In this study, soils spiked with copper oxide nanoparticles (CuO NPs) or Cu(NO3)2 and aged as long as 90 days were utilized to investigate effect of soil properties and aging on oral and inhalation bioaccessibility of CuO NPs. Results showed that oral bioaccessibility of CuO NPs in gastric phase (GP) ranged from 70% to 84%, it significantly decreased to 50%-70% in intestinal phase (IP). The inhalation bioaccessibility of CuO NPs in artificial lysosomal fluid (ALF) ranged from 66% to 85%, and much higher than that in Gamble's solution (GS, 3.3%-23%). By comparing CuO NPs to Cu(NO3)2 bioaccessibility, insignificant difference was found. The aging time (D15 and D90) had limited effect on their oral and inhalation bioaccessibility. CEC and free Al were positively and clay content was negatively correlated with CuO NPs inhalation bioaccessibility, while Cu(NO3)2 inhalation bioaccessibility decreased with increasing soil clay content and pH. Our findings provide an essential basis to evaluate the human health risks of CuO NPs.

Ameliorative role of curcumin on copper oxide nanoparticles-mediated renal toxicity in rats: An investigation of molecular mechanisms.

The increasing role of copper oxide nanoparticles (CuO NPs) in many industries and their broad range of applications increase its potential toxic effects. Curcumin possesses a wide range of health benefits. This study aimed to evaluate the role of curcumin in attenuating CuO NPs toxicity in rat kidney. Thirty six animals were divided into five groups; control groups (I, II), curcumin group orally received curcumin 200 mg/kg bw, CuO NPs group orally gavaged 250 mg/kg bw CuO NPs and combined group orally gavaged curcumin and CuO NPs. Treatment was given for 3 months. Administration of CuO NPs revealed elevation in serum creatinine and blood urea nitrogen levels, elevated kidney and urine levels of kidney injury molecule-1, decreased catalase, superoxide dismutase activities, total sulfhydryl, reduced glutathione content, increased serum reactive oxygen species, tissue total oxidant status, lipid hydroperoxides, protein carbonyl, malondialdehyde, nitric oxide levels, increased interleukin-1ß, tumor necrosis factor-α, nuclear factor (NF-κB), and decreased heme oxygenase-1 (HO-1) and γ-glutamylcysteine synthetase (γ-GCS) genes expression. Moreover, histopathological alteration in kidney structure was detected. Immunohistochemical-stained sections by caspase-3 reaction revealed apoptosis. Pretreatment with curcumin improved most of the adverse effects in rats treated with CuO NPs regarding oxidative stress and inflammatory indices in kidney, and kept histopathological- and immunohistochemical-stained sections near to normal. This study shows that curcumin administration attenuates the toxicity in the kidney of CuO NPs-treated rats through its antioxidant, anti-inflammatory, and antiapoptotic effects.

Phytotoxicity Assessment of Copper Oxide Nanoparticles on the Germination, Early Seedling Growth, and Physiological Responses in Oryza sativa L.

The increasing utilization of copper oxide nanoparticles (CuO NPs) and their release into the environment has made it imperative to elucidate their impact on the ecological system including plants. However, their potential toxic impact and mechanisms on plant growth are still unclear. The aim of this study was to investigate the effects of CuO NPs and released Cu ions on seed germination and early seedling growth, as well as physiological and biochemical parameters of Oryza sativa. The results showed that CuO NPs at high concentration significantly inhibited seed germination and early seedling growth. The toxicity of CuO NPs originated from the particulate NPs rather than the released Cu2+. The phytotoxicity of CuO NPs to rice seed germination and seedling growth probably induced by high Cu accumulation along with the lignification and oxidative damage. The work presented here will increase our knowledge of phytotoxicity of CuO NPs.

Acute and subacute oral toxicity of copper oxide nanoparticles in female albino Wistar rats.

The extensive use of copper oxide nanoparticles (CuO-NPs) in various industries and their wide range of applications have led to their accumulation in different ecological niches of the environment. This excess exposure raises the concern about its potential toxic effects on various organisms including humans. However, the hazardous potential of CuO-NPs in the literature is elusive, and it is essential to study its toxicity in different biological models. Hence, we have conducted single acute dose (2000 mg/kg) and multiple dose subacute (30, 300 and 1000 mg/kg daily for 28 days) oral toxicity studies of CuO-NPs in female albino Wistar rats following OECD guidelines 420 and 407 respectively. Blood analysis, tissue aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and acetylcholinesterase, superoxide dismutase, catalase, lipid malondialdehyde and reduced glutathione assays, and histopathology of the tissues were carried out. The higher dose treatments of the acute and subacute study caused significant alterations in biochemical and antioxidant parameters of the liver, kidney and brain tissues of the rat. In addition, histopathological evaluation of these three organs of treated rats showed significantly high abnormalities in their histoarchitecture when compared to control rats. We infer from the results that the toxicity observed in the liver, kidney and brain of treated rats could be due to the increased generation of reactive oxygen species by CuO-NPs.

Liquid assisted pulsed laser ablation synthesized copper oxide nanoparticles (CuO-NPs) and their differential impact on rice seedlings.

Hydroponic experiments were conducted to investigate impact of laser ablated copper oxide nanoparticles (CuO-NPs) on rice seedlings. The present work demonstrates that exposure of lower concentrations (5, 10, 20, and 50 µM) of CuO-NPs enhance growth (in terms of fresh and dry weight and length), of rice seedlings. However, at higher concentrations (100, 200, and 500 µM) of CuO-NPs, growth (in terms of length, fresh weight and dry weight) decreased significantly (P < 0.05). Further, photosynthetic pigments (total chlorophyll and carotenoids) and protein contents were also found to be in accordance with the results of growth. This had occurred due to enhanced level of CuO-NPs accumulation at higher doses which also enhanced the level of oxidative stress markers such as hydrogen peroxide (H2O2) and malondialdehyde (MDA). Chlorophyll a fluorescence parameters (Fv/Fm and qP and except NPQ) and amount of some minerals (Ca, Mg, Na, and K) increased at lower concentrations of CuO-NPs. In contrast, the levels of Fv/Fm and qP were significantly (P < 0.05) reduced at higher concentration of CuO-NPs, which might be due to enhanced accumulation of Cu and oxidative stresses markers. Our results showed that lower dosages of pulsed laser ablated CuO-NPs (5, 10, 20, and 50 µM) might be beneficial for growth and development of rice seedlings.