Doses Of Cu Research Articles

Long-term Copper Exposure Induces Mitochondrial Dynamics Disorder and Mitophagy in the Cerebrum of Pigs.

Copper (Cu) is an essential trace element for growth and development in most organisms. However, environmental exposure to high doses of Cu can damage multiple organs. To investigate the underlying mechanism of Cu toxicity on mitochondrial dynamics and mitophagy in the cerebrum of pigs, 60 30-day-old pigs were randomly divided into three groups and treated with different contents of anhydrous Cu sulfate in the diets (Cu 10mg/kg, control group; Cu 125mg/kg, group I; Cu 250mg/kg, group II) for 80days. The Cu levels and histological changes in the cerebrum were measured. Moreover, the protein and mRNA expression levels related to mitophagy and mitochondrial dynamics were determined. The results showed that the contents of Cu were increased in the cerebrum with increasing dietary Cu. Vacuolar degeneration was found in group I and group II compared to the control group. Additionally, the protein and mRNA expression levels of PINK1, Parkin, and Drp1 and the protein level of LC3-II were remarkably upregulated with increasing levels of dietary Cu. Nevertheless, the protein and mRNA expression levels of MFN1 and MFN2 and the mRNA expression of P62 were obviously downregulated in a Cu dose-dependent manner. Overall, these results suggested that excess Cu could trigger mitochondrial dynamics disorder and mitophagy in the pig cerebrum, which provided a novel insight into Cu-induced toxicology.

Copper oxide nanoparticles trigger macrophage cell death with misfolding of Cu/Zn superoxide dismutase 1 (SOD1)

BackgroundCopper oxide (CuO) nanoparticles (NPs) are known to trigger cytotoxicity in a variety of cell models, but the mechanism of cell death remains unknown. Here we addressed the mechanism of cytotoxicity in macrophages exposed to CuO NPs versus copper chloride (CuCl2).MethodsThe mouse macrophage cell line RAW264.7 was used as an in vitro model. Particle uptake and the cellular dose of Cu were investigated by transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS), respectively. The deposition of Cu in lysosomes isolated from macrophages was also determined by ICP-MS. Cell viability (metabolic activity) was assessed using the Alamar Blue assay, and oxidative stress was monitored by a variety of methods including a luminescence-based assay for cellular glutathione (GSH), and flow cytometry-based detection of mitochondrial superoxide and mitochondrial membrane potential. Protein aggregation was determined by confocal microscopy using an aggresome-specific dye and protein misfolding was determined by circular dichroism (CD) spectroscopy. Lastly, proteasome activity was investigated using a fluorometric assay.ResultsWe observed rapid cellular uptake of CuO NPs in macrophages with deposition in lysosomes. CuO NP-elicited cell death was characterized by mitochondrial swelling with signs of oxidative stress including the production of mitochondrial superoxide and cellular depletion of GSH. We also observed a dose-dependent accumulation of polyubiquitinated proteins and loss of proteasomal function in CuO NP-exposed cells, and we could demonstrate misfolding and mitochondrial translocation of superoxide dismutase 1 (SOD1), a Cu/Zn-dependent enzyme that plays a pivotal role in the defense against oxidative stress. The chelation of copper ions using tetrathiomolybdate (TTM) prevented cell death whereas inhibition of the cellular SOD1 chaperone aggravated toxicity. Moreover, CuO NP-triggered cell death was insensitive to the pan-caspase inhibitor, zVAD-fmk, and to wortmannin, an inhibitor of autophagy, implying that this was a non-apoptotic cell death. ZnO NPs, on the other hand, triggered autophagic cell death.ConclusionsCuO NPs undergo dissolution in lysosomes leading to copper-dependent macrophage cell death characterized by protein misfolding and proteasomal insufficiency. Specifically, we present novel evidence for Cu-induced SOD1 misfolding which accords with the pronounced oxidative stress observed in CuO NP-exposed macrophages. These results are relevant for our understanding of the consequences of inadvertent human exposure to CuO NPs.

Superior Pharmacokinetic Profile of an Innovative, Next Generation Curcumin Formula

IntroductionCurcumin is the major bioactive component of turmeric or Curcuma longa L., a widely used spice, food colorant, preservative as well as medicinal agent in Indian and Chinese remedies. Numerous studies have demonstrated its potential benefits for heart health, immunity, diabetes, arthritis as well as joint health and mobility. Currently, curcumin‐based products in capsules, ointments, tablets, and cosmetics are marketed worldwide. One important drawback of using curcumin is its poor bioavailability and hence the need to use it at high doses to achieve measurable plasma levels and efficacy – this limits both consumer compliance and product formulation. Curcumin’s poor solubility, low absorption from the gut, rapid metabolism and rapid systemic elimination contributes to its poor bioavailability. To help overcome this major limitation of curcumin, we developed a proprietary curcumin formulation (Curcuwin Ultra+) (CU+) to enhance its bioavailability. We hypothesized that the formulation would protect the curcuminoids from degradation at intestinal alkaline pH conditions, and through this mechanism, significantly increase the availability of curcuminoids in blood and at the tissue level.GoalOur goal was to measure the pharmacokinetic profile of CU+ vs. a standard turmeric extract (STE).MethodA randomized, double‐blind, crossover study design involving 24 healthy volunteers under fasting conditions was implemented. Subjects received a single dose of 250 mg CU+, 500 mg CU+ and 1900 mg of STE. Blood samples before dosing, and at various time points post dosing up to 24 hours were collected. Total curcuminoids were measured using a validated LC‐MS/MS method. Formulations were compared based on Cmax, AUC0‐6, AUC0‐24, Tmax, t1/2, and relative absorption.ResultsMaximum serum concentration (Cmax) and total systemic exposure (AUC0‐6 and AUC0‐24) for total curcuminoids were significantly higher (p<0.05) for both doses of CU+ vs. STE. For example, AUC0‐6 was 144 and 149 times greater for CU+ at 250 mg and 500 mg respectively compared to 1900 mg of STE. Additionally, CU+ showed 40% faster absorption as measured by Tmax vs. the STE (p<0.05). No adverse events were observed.ConclusionsThese pharmacokinetic data demonstrates the ability of this curcumin formulation to deliver superior bioavailability vs. STE, and, at doses that are considerably lower than STE and several other commercially available curcumin products. This has important relevance to consumer compliance in terms of lowering curcumin dose and frequency of dosing. Since maximizing bioavailability influences the therapeutic effects of a compound, the next phase of our research program is to determine if this enhanced bioavailability can be translated to an efficacious benefit of CU+.

Superior Bioavailability of a Novel Curcumin Formulation in Healthy Humans Under Fasting Conditions.

BackgroundDespite its broad range of biological activities, use of curcumin is limited because of poor bioavailability. Here we report a novel curcumin formulation, Curcuwin Ultra+ (CU+), with superior bioavailability as compared to 95% turmeric extract (TUR 1800).MethodsA randomized, double-blind, three-treatment, crossover oral bioavailability study was conducted in 24 healthy volunteers under fasting conditions. Subjects received a single dose of CU+ 250 mg, 500 mg and 1900 mg of TUR1800 as per randomization schedule and blood samples were collected at 4 h and 0 h before dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post dose. Total curcuminoids were measured as curcumin, demethoxycurcumin, bisdemethoxycurcumin, and tetrahydrocurcumin using a validated LC–MS/MS method.ResultsCU+ achieved a significantly higher (p < 0.05) maximum plasma concentration (Cmax) and total systemic exposure (AUC0–6 and AUC0–12) for total curcuminoids as compared to TUR 1800. We observed 101 and 100 times higher Cmax respectively for 250 and 500 mg doses of CU+ as compared to 1900 mg of TUR1800. Similarly, AUC0–6 was 144 and 149 times higher whereas AUC0–12 was 99 and 113 times higher respectively for 250 and 500 mg doses of CU+ as compared to 1900 mg dose of TUR1800. Further, CU+ showed 40% faster absorption (p < 0.05). No safety issues were observed.ConclusionCU+, which is designed for increased absorption and protection of curcuminoids from intestinal degradation, demonstrated superior bioavailability as compared to TUR1800 at considerably smaller doses. Additional clinical studies will help to demonstrate the impact of its increased bioavailability on efficacy.Clinical Trial RegistrationCTRI/2020/10/028508 (Clinical Trials Registry—India).

Dietary Copper Requirements for Aquatic Animals: A Review.

Copper (Cu) is a vital microelement required for the optimum growth performance and wellbeing of aquatic animals. It contributed to various biological, physiological, and metabolic function in the entire body of the aquatic animals. Further, Cu is a cofactor for several enzymes involved in the antioxidation capacity and metalloenzyme formation. Some ingredients used for aquafeed formulation include sufficient amounts of Cu that can provide aquatic animals with their requirements. Nevertheless, in some cases, external Cu sources are needed to optimize the essential needs of aquatic animals. Inorganic, organic, and nano Cu forms are included in aquafeed and result in regulated physiological and biological functions. The addition of Cu should be added at particular doses considering the species, size, duration, and environmental conditions. Water-borne Cu level should also be considered as long as aquatic animals can obtain their requirements through gills to avoid overdosing and toxicity. Several studies reported the optimum doses of Cu required for optimal growth, productivity, and health status in several aquatic animals. This review article presents the up-to-date results of Cu-related studies in aquafeed. It also helps academia design further studies to better understand the border between Cu requirements and toxicity. Besides, planning for more studies involved in the understanding of the primary mode of action of Cu in aquatic animals' entire bodies.

Variation of Some Plant Growth Parameters in Coriander (Coriandrum sativum L.) with Copper Application

This study was carried out to investigate the effect of different copper (Cu) concentrations on some plant growth parameters in coriander (Coriandrum sativum L.). The study was perfomed at the Agricultural Biotechnology growth room, Faculty of Agriculture, Siirt University (Turkey). In the study, the coriander Mardin province population was used as plant material. Five different doses of Cu (0, 100, 200, 300, and 400 ppm) were applied to plants. Plant height (cm), stem diameter (mm), the number of branches per plant, the number of umbel per plant, the number of seeds in the main umbel, plant fresh, and dry weights (g) were determined. According to the results, the effect of different Cu concentrations in all growth parameters except stem diameter and number of branches were found to be significant. In the current study, plant height, stem diameter, number of branches, number of umbel, number of seeds in the main umbel, and plant fresh weight and dry weights were ranged between 41.31-52.79 cm, 1.57-2.18 mm, 3.07-5.71 per plant, 2.57-4.86 per plant, 13.36-37.86 per plant, 2.33-4.12 g and 0.239-0.550 g, respectively. In the study, it was concluded that coriander can be included in phytoremediation programs in Cu-contaminated areas.

The Impact of Zn, Cu and Fe Chelates on the Fatty-Acid Profile and Dietary Value of Broiler-Chicken Thigh Meat

Simple SummaryPoultry meat is deemed a product with a dietary value. The chemical composition of meat can be altered by modifying animals’ diets. Our objective was to show the impact of the addition of glycine chelates of minerals (Zn, Cu, Fe) to broiler chickens’ feed on the fatty-acid profile and dietary value of thigh meat. A positive effect was most frequently noted for Zn chelate, especially in a larger dose. The lowest levels of saturated fatty acids and atherogenic and thrombogenic indices but the highest content of polyunsaturated fatty acids n−3 and polyunsaturated fatty acids/saturated fatty acid ratios and hypocholesterolemic/hypercholesterolemic indices were noticed. The use of Cu and Fe glycine chelates was worse than Zn but did not meet the levels from the control group. These types of treatments are important in order to ensure correct functions of the body and can mitigate or even prevent the occurrence of many diseases.This study aimed to compare the effect of Zn, Cu and Fe glycine chelates on the proximate composition, cholesterol levels, fatty-acid profile and dietary value of the thigh meat of broiler chickens. The experiment involved three hundred and fifty Ross 308 chickens divided into seven groups. The chickens were administered Zn, Cu and Fe glycine chelates in an amount corresponding to 50% of the requirement or 25% of the requirement for 42 days. It was found that the use of Zn, Cu and Fe glycine chelates did affect the fatty acid profile and dietary value of meat. A positive impact was most frequently (p < 0.05) noted in chickens receiving Zn chelate in an amount covering 50% of the requirement: the lowest levels of SFA and atherogenic and thrombogenic indices, the highest content of PUFA n−3 and PUFA/SFA ratios and hypocholesterolemic/hypercholesterolemic indices. Positive effects were more often recorded for chickens receiving Zn in an amount corresponding to 50% of the requirement. The results did not show that the use of Cu and Fe glycine chelates can reduce the dietary value of thigh meat in broiler chickens since, generally, the outcomes were not worse than those in the control group. It should be highlighted that due to ambiguous results, it is impossible to determine a dose of Cu and Fe glycine chelate which would be more efficient for broiler chickens. However, chickens receiving chelates in amounts corresponding to 25% of the requirement showed far better results.

Ultra-fast Cu-based A3-coupling catalysts: faceted Cu2O microcrystals as efficient catalyst-delivery systems in batch and flow conditions

Cu(I) catalysts were studied for the synthesis of a propargylamine via A3-coupling of aldehyde, amine, and alkyne, under solvent-free and low loading conditions, using batch microwave or flow thermal heating. We explored ultra-low loading conditions with Cu(I) salts as fast and active catalysts featuring turnover frequencies (TOFs) above 105 h−1. Well-defined octahedral and cubic Cu2O microcrystals were also successfully applied and compared with this reaction. Both types of microcrystals exhibited excellent catalytic activities within minutes, via in situ generation of low dose of Cu(I) ions within the reaction medium, to achieve TON beyond 2000 and recycling up to 10 times in a flow reactor. The study of the catalytic system demonstrated that the activity was surface-structure dependent and allowed for the design of low Cu contamination A3-coupling systems, affording a product at the decigram scale, with Cu contamination below FDA recommendations for drug synthesis, without the need for a purification procedure.

474 Comparison Between Copper Sulfate and Dicopper Oxide on Body Weight and Copper Accumulation on Growing Pigs

Abstract There are several Cu sources in the market that have different effects on pigs. We hypothesized that supplementing therapeutic doses of Cu(I)oxide (Cu2O) in diets for growing pigs improves body weight (BW), bone mineralization, and reduces Cu accumulation in liver than supplementing pigs with Cu sulfate (CuSO4). Two-hundred growing pigs (initial BW: 11.5 ± 0.98 kg) were randomly allotted to 5 dietary treatments. Dietary treatments included the negative control (NC) diet without Cu supplementation, and 4 diets in which 125 or 250 mg/kg of Cu from CuSO4 or Cu2O were added to the NC diet. The experiment was divided into 4 phases. Pig weights were recorded on d 1 and at the end of each phase. Eight pigs per treatment were sacrificed last d of phases 1 and 4 to obtain samples of liver, spleen, and the right metacarpal. Pigs fed diets containing 250 mg/kg of Cu2O had greater (P &amp;lt; 0.05) BW at the end of phases 1 and 2 than pigs fed the NC diet, and tended (P &amp;lt; 0.10) to have greater BW at the end of phases 3 and 4 than pigs fed the other diets. Copper accumulation in liver and spleen increased with Cu dose, but at the end of phase 1, pigs fed 250 mg/kg CuSO4 had greater (P &amp;lt; 0.05) Cu concentration in liver and spleen than pigs fed 250 mg/kg Cu2O. Pigs fed diets containing 250 mg/kg Cu2O had greater (P &amp;lt; 0.05) quantities of bone ash and greater (P &amp;lt; 0.05) concentrations of Ca, P, and Cu in bone ash than pigs fed the NC diets or diets containing CuSO4. Therefore, supplementing diets for growing pigs with therapeutic doses of Cu2O improves BW and bone mineralization with less Cu accumulation in liver compared with pigs fed diets containing CuSO4.

Effects of Multiple, Low‐Dose Copper Sulfate Treatments on the Marsh Rams‐Horn Snail

AbstractBolbophorus damnificus has caused epizootics in catfish aquaculture since the mid‐1990s. To mitigate the losses that are associated with trematode infestations, research has focused on eradicating snails from ponds. Whole‐pond treatments with 0.64–1.27 mg/L Cu have been effective in killing snails; however, Cu can be toxic to fish and may result in oxygen depletions due to its algacidal properties. Given these constraints, the potential for repeated low doses of Cu as a safe, yet effective snail treatment was investigated. Adult marsh rams‐horn snails Planorbella trivolvis received four weekly doses of 0, 0.10, 0.19, 0.38, and 0.76 mg/L Cu. All of the snails died after the first treatment of 0.76 mg/L Cu. The lowest doses of 0.10 and 0.19 mg/L Cu resulted in 68% and 88% cumulative mortality, respectively. This experiment was repeated with laboratory‐reared adult marsh rams‐horn snails in two different laboratories, resulting in 100% mortality in the 0.38 mg/L Cu treatment. A second study evaluated the effects of repeated Cu doses on egg and juvenile snail survival. Two weekly doses of 0.19 mg/L Cu were enough to kill embryos, and all of the doses ≥0.05 mg/L Cu prevented the snails from hatching. In a pond trial, 0.51 mg/L Cu killed 100% of the adult snails after two doses. The lowest dose of 0.13 mg/L Cu killed 60% of the snails after three doses. Repeated weekly doses &lt;0.38 mg/L Cu may reduce adult snail populations, prevent eggs from hatching, and be safer for fish than a single dose of 0.64–1.27 mg/L Cu. These data also suggest that weekly doses &lt;0.05 mg/L Cu may suppress marsh rams‐horn snail populations by limiting hatching and impeding juvenile survival.

Copper exposure induces hepatic G0/G1 cell-cycle arrest through suppressing the Ras/PI3K/Akt signaling pathway in mice

Copper (Cu), as a common chemical contaminant in environment, is known to be toxic at high concentrations. The current research demonstrates the effects of copper upon hepatocyte cell-cycle progression (CCP) in mice. Institute of cancer research (ICR) mice (n = 240) at an age of four weeks were divided randomly into groups treated with different doses of Cu (0, 4, 8, and 16 mg/kg) for 21 and 42 days. Results showed that high Cu exposure caused hepatocellular G0/G1 cell-cycle arrest (CCA) and reduced cell proportion in the G2/M phase. G0/G1 CCA occurred with down-regulation (p < 0.05) of Ras, p-PI3K (Tyr458), p-Akt (Thr308), p-forkhead box O3 (FOXO3A) (Ser253), p-glycogen synthase kinase 3-β (GSK3-β) (Ser9), murine double minute 2 (MDM2) protein, and mRNA expression levels, and up-regulation (p < 0.05) of PTEN, p-p53 (Ser15), p27, p21 protein, and mRNA expression levels, which subsequently suppressed (p < 0.05) the protein and mRNA expression levels of CDK2/4 and cyclin E/D. These results indicate that Cu exposure suppresses the Ras/PI3K/Akt signaling pathway to reduce the level of CDK2/4 and cyclin E/D, which are essential for the G1-S transition, and finally causes hepatocytes G0/G1 CCA.

Influence of Copper Contamination on Soil Physico-chemical Properties, Microbial Population and Enzyme Activities

Heavy metals are known for their phytotoxicity and commonly used in agrochemicals to control plant pathogens. Accumulation of heavy metals in soil may occur through extensive use of heavy metal-based agrochemicals over time or from industrial pollution. However, this study was focussed on the immediate effect of the heavy metal, Copper (Cu) contamination on soil microbial population and soil enzyme activities (viz. acid phosphatase, β-glucosidase, urease &amp; dehydrogenase). Soil with graded doses of Cu was prepared by treating soil samples with varying concentrations of Copper (ll) sulphatepentahydrate (CuSO4.5H2O) where three levels of CuSO4.5H2O (50, 100 &amp; 200 mg/kg soil) treatments were formulated along with control. A significant decrease in soil microbial population and soil enzyme activities was observed in all treatments.

Studying the Influence of Copper on the Growth Behavior, Antioxidative Status, and Histology of the Intestine and Liver of Striped Catfish (Pangasianodon hypophthalmus).

Microelements are well recognized as an essential approach in the field of aquaculture nutrition. Thus, this study aimed to evaluate copper (Cu) inclusion (0, 0.5, 1, and 2 mg/kg) on Striped catfish performances. Fish fed the Cu-incorporated diets for 60 days, then their growth behavior, antioxidative capacity, and intestinal and liver histological features were evaluated. The results showed a marked enhancement in Striped catfish's growth behavior fed 1-2 mg/kg of Cu, as shown by the final weight, weight gain, and specific growth rate. The feed and protein efficiency ratios were significantly affected by Cu in a dose-dependent manner. The highest level of Cu was accumulated in the whole body, muscle, liver, and gills of fish fed 2 mg/kg of Cu. The carcass composition of Striped catfish showed higher protein content in groups received 0.5, 1, and 2 mg/kg Cu in a linear and quadratic manner (p=0.001). The ash content was quadratically increased in Striped catfish fed 2 mg/kg Cu (p=0.001). However, no marked effects were observed on the moisture and lipid contents and the somatic indices (p>0.05). The incorporation of Cu showed meaningfully increased superoxide dismutase, catalase, and glutathione peroxidase but decreased malondialdehyde level in Striped catfish. The villous height exhibited visible growth and branching with increased doses of Cu without a significant increase in the goblet cells. No abnormal features were observed in the liver and hepatocytes of fish treated with Cu. It can be concluded that Cu is required at 1-2 mg/kg for better performances of Striped catfish.

Metal Accumulation Profile of Catharanthus roseus (L.) G.Don and Celosia argentea L. with EDTA Co-Application

The problem of metal-induced toxicity is proliferating with an increase in industrialization and urbanization. The buildup of metals results in severe environmental deterioration and harmful impacts on plant growth. In this study, we investigated the potential of two ornamental plants, Catharanthus roseus (L.) G.Don and Celosia argentea L., to tolerate and accumulate Ni, Cr, Cd, Pb, and Cu. These ornamental plants were grown in Hoagland’s nutrient solution containing metal loads (50 µM and 100 µM) alone and in combination with a synthetic chelator, ethylenediaminetetraacetic acid (EDTA) (2.5 mM). Plant growth and metal tolerance varied in both plant species for Ni, Cr, Cd, Pb, and Cu. C. roseus growth was better in treatments without EDTA, particularly in Ni, Cr, and Pb treatments, and Pb content increased in all parts of the plant. In contrast, Cd content decreased with EDTA addition. In C. argentea, the addition of EDTA resulted in improved plant biomass at both doses of Cu. In contrast, plant biomass reduced significantly in the case of Ni. In C. argentea, without EDTA, root length in Cd and Cu treatments was significantly lower than the control and other treatments. However, the addition of EDTA resulted in improved growth at both doses for Pb and Cu. Metal accumulation in C. argentea enhanced significantly with EDTA addition at both doses of Cu and Cd. Hence, it can be concluded that EDTA addition resulted in improved growth and better metal uptake than treatments without EDTA. Metal accumulation increased with EDTA addition compared to treatments without EDTA, particularly for Pb in C. roseus and Cu and Cd in C. argentea. Based on the present results, C. roseus showed a better ability to phytostabilize Cu, Cd, and Ni, while C. argentea worked better for Ni, Cd, Cu, and Pb.

Counteracting the Negative Effects of Copper Limitations Through the Biostimulatory Action of a Tropical Plant Extract in Grapevine Under Pedo-Climatic Constraints

In southern Mediterranean areas, vineyards are facing the combination of increasing air temperature, drought and frequency of extreme events (e.g., heat waves) due to climate change. Since most of the berry growth and ripening phases occur during the aridity period, such environmental constraints are responsible for limitations in yield and berry quality. Within this scenario, to achieve vineyard sustainability, renewed approaches in vineyard management have been proposed and the use of plant biostimulants seems a prominent and environmental friendly practice. The aim of this study was to test four combinations of a tropical plant extract and conventional chemicals for disease control on morpho-anatomical, physiological, biochemical and berry quality inVitis viniferaL. subsp.vinifera“Aglianico.” In particular, we aimed to evaluate the possibility to counteract the negative effects of the reductions in copper distribution, by applying the tropical plant extract enriched with: micronutrients, enzymes involved in the activation of natural defense, aminoacids, and vitamins. The halved dose of Cu in combination with the tropical plant extract allowed maintaining a reduced vegetative vigor. In the second year of treatment, the addition of the plant extract significantly improved leaf gas exchanges and photochemistry as well as the synthesis of photosynthetic pigments. At berry level, the plant extract induced an increase in phenolics accompanied by a decrease in soluble sugars. The overall results showed that the expected differences in growth performance and productivity in vines are linked to different eco-physiological and structural properties induced by the various treatments. The tropical plant extract also primed plant defenses at the leaf and fruit levels, mainly due to modifications of some structural and biochemical traits, respectively.

Zn Induces Lipophagy via the Deacetylation of Beclin1 and Alleviates Cu-Induced Lipotoxicity at Their Environmentally Relevant Concentrations.

In this study, the mechanisms of environmentally relevant doses of Cu and Zn mixtures influencing lipid deposition and metabolism were investigated in freshwater teleost yellow catfish Pelteobagrus fulvidraco (2 months old, 4.95 (t0.01 g, mean ± SEM). Our study indicated that waterborne Cu exposure increased lipid content, while Zn activated lipophagic flux and alleviated Cu-induced lipid accumulation. Yellow catfish hepatocytes treated with Zn or Zn + Cu activated autophagy-specific lipophagy, decreased lipid storage, and increased nonesterified fatty acid (NEFA) release, suggesting a causal relationship between lipophagy and lipid droplet (LD) breakdown under Zn and Zn + Cu conditions. Our further investigation found that Beclin1 deacetylation by sirtuin 1 (SIRT1) was required for Zn- and Zn + Cu-induced lipophagy and lipolysis, and lysine residues 427 and 434 were key sites for Beclin1 deacetylation. Taken together, these findings show that the Zn-induced deacetylation of Beclin1 promotes lipophagy as an important pathway to alleviate Cu-induced lipid accumulation in fish, which reveals a previously unidentified mechanism for understanding the antagonistic effects of Cu and Zn on metabolism at their environmentally relevant concentrations. Our results highlight the importance of combined exposure when the biological effects of heavy metals are evaluated during environmental risk assessments.

Effects of hot-melt extruded nano-copper on the Cu bioavailability and growth of broiler chickens.

This study was aimed to investigate the Cu bioavailability, growth response, digestibility of nutrients, and blood metabolites of broiler chicks fed CuSO4 in nano or common forms. A total of 720 broiler chickens were distributed between eight treatments according to a completely randomized design. There were 8 treatments and 6 replicates in each treatment with 15 birds/replicate. The treatments were divided into common copper sulfate at the doses of 16 ppm, 40 ppm, 80 ppm, and 120 ppm (INO) and hot-melt extruded copper sulfate at the doses of 16 ppm, 40 ppm, 80 ppm, and 120 ppm (HME-Cu). The experiment was operated for 35 days in 2 phases (phase 1, d 0 to 14; and phase 2, d 15 to 35). No significant differences were shown in growth performance, feed intake, FCR, and nutrient digestibility among the treatments. The concentration of Cu in the serum was increased in the HME-Cu broilers compared with the INO broilers at phase 2. A linear increase was observed in the concentration of Cu in the liver in broilers fed INO diets, however, no significant differences were observed by the supplementation of HME-Cu levels. The linear increase was detected in the content of Cu in excreta in the INO and HME-Cu treatments by increasing the dietary Cu content. The HME-Cu treatments showed a lower Cu concentration in the excreta compared with the INO treatments. The higher bioavailability of Cu in HME form can decrease the recommended dose of Cu in broiler diets.

Physiological responses of Vicia faba to copper toxicity

Abstract. Copper plays an important role in multiple plant physiological processes including photosynthesis and protein synthesis. Excess copper in tissues leads to physiological and biochemical disturbances. In order to determine the physiological response of Vicia faba L. to copper toxicity, two varieties (Sidi Aïch and Super Aguadulce) were grown in a substrate of sand and compost (3V/V) and contaminated by different doses of Cu (0, 80, 160, 240, 320, 400 mg kg-1). Dose rates ≥160 mg kg-1 led to the accumulation of copper in roots and shoots, in turn leading to decreases in photosynthetic activity and protein content and to the accumulation of proline, a stress indicator, and soluble sugars.

Chronic tribasic copper chloride exposure induces rat liver damage by disrupting the mitophagy and apoptosis pathways

Despite the fact that copper (Cu) is a vital micronutrient to maintain body function, high doses of Cu through environmental exposure damage various organs, especially the liver, which is the main metabolic organ. To investigate the influence of long-term Cu-induced toxicity on mitophagy and apoptosis in rat liver, 96 seven-month-old male Sprague-Dawley rats were fed TBCC for 24 weeks. The results revealed that exposure to high Cu concentrations could promote oxidative stress liver injury by increasing the hepatic function index (ALT, AST and ALP) and MDA content, while reducing the activity of antioxidant enzymes (T-SOD, GSH-Px and CAT) related to oxidative stress. Consistent with histopathological observations, proper dietary Cu (15–60 mg/kg) could improve antioxidant stress levels and induce a dose-dependent increase in the mRNA expression of mitophagy-related genes, whereas a high Cu concentration (120 mg/kg) could cause severe liver impairment and ultrastructural changes and a reduction in mitophagosomes, accompanied by downregulation of Atg5, Beclin1, Pink1, Parkin, NIX, P62 and LC3B. The expression of apoptosis-related genes (Bax, Bax/Bcl-2, Caspase3, Cytc and p53) and proteins (Caspase3 and p53) was upregulated with the addition of dietary Cu. The results demonstrated that an appropriate dose of TBCC could improve liver function by promoting mitophagy and Cu enzymes that play antioxidative roles, while the accumulation of excess Cu could induce liver lesions by enhancing apoptosis and inhibiting mitophagy pathways.

Concentration, composition, and exposure contributions of fine particulate matter on subway concourses in China.

Concentrations of airborne metal-rich particles are typically higher on subway platforms and in subway tunnels than in ambient air. The subway concourse is an area of direct air exchange with both platforms and the outside environment, but few researchers have measured the concentrations and composition of fine particles on subway concourses. We characterized the concentrations and composition of fine particles on six subway concourses in Nanjing, China in both summer and winter. We used a respiration rate-adjusted microenvironment exposure model to estimate the contribution of a 6-h work period to daily mean exposure to fine particulate matter of subway workers and compared the estimate with those for general indoor and outdoor workers. We found that particle concentrations were typically higher on the station concourses than in ambient air. The most abundant elements composing the particles were Fe, S, Ca, Si, and K in both subway concourses and reference ambient air, but their contents varied greatly between indoor and outdoor air. The indoor/outdoor ratios of Fe, Cu, and Mn were highest, and subway workers were disproportionately exposed to these three metals. The mean daily exposure dose to Fe was 44.8μg for subway workers, approximately five times the exposure dose of indoor and outdoor workers. Daily exposure doses of Cu, Mn, V, Sr, As, Co, Sn, and Cr were also higher for subway workers. The quality of indoor air at subway stations is therefore of occupational health concern and strategies should be formulated to reduce worker exposure.