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... Conversely, (32,5) found an increase in body weight gain in goat kids supplemented with organic Cu, compared with inorganic Cu. In a recent meta-analysis (33). The assessment of the benefits of organic trace minerals, only marginal improvements in the production of milk, the fat content of the milk and milk proteins have been found. ...
... Other parameters, including the effectiveness of the diet, the index of consumption, the humoral and cell mediated immune response and the ceruloplasmin activity, have not been affected by the Cu source (25,36). Organic sources of Cu have been seriously criticized by (33) who consider that the technologies of protection against the rumen antagonisms are extravagant and provide no any other advantage than conventional CuSO4. According to (30) led to commercial purposes, the continuation of benefits compared to insignificant cheap and effective to inorganic Cu sources must stop, and focus should be on the prediction of the necessary supplementation, rather than under-supply of Cu and its impact on the environment (24). ...
... However, these technologies seem to be more effective in monogastric animals that in ruminants. Mechanisms to ensure an optimal level of ruminally available minerals, and optimize the supply of minerals to the lower gastrointestinal tract without compromising the post-ruminal absorption require research further (33,37). ...
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The key component in striving towards optimum animal production are possible by the provision of essential nutrients such as protein, carbohydrates, fats, minerals and vitamins to livestock in a balance pattern. The important role of trace minerals in term of animal production is far away very much highlighted broadly, as the trace elements are recognized with the most significant functional components of numerous metabolic processes. The body has the basic needs of trace minerals in trace amounts, ranging from 0.10 to 50.0 mg/kg of dry matter in the feed of dairy animals. These trace elements are essential for all biochemical processes of the body that supports the growth and the appropriate maintenance. Such as, copper (Cu) is necessary for the function of the superoxide dismutase and in the removal of toxic by-products of metabolic pathways. The exclusion of these toxic by-products permits metabolism to perform efficiently, uninhibited by damaging oxygen free radicals. Manganese(Mn), an essential trace mineral, important for development, metabolism, in the antioxidant system and has a slight effect on stimulating the activity of the Urease. Zinc (Zn), a significant trace mineral for the enzymatic function, help in the regulation of the production of nucleic acid, the metabolism of carbohydrates and protein synthesis, thus providing a stable framework for the development. Generally, Legume forages, grains, dairy rations an d dietary trace mineral complexes are the fair sources of these trace minerals to meet the requirements of livestock. The immune system is part of the defense of the host against the destructive forces from the outside of the body, such as bacteria, fungi, parasites and viruses, or of the Interior, such as the malignant cells or those who produce auto-antibodies. Trace minerals have an important role for normal immune function and disease resistance including zinc, copper and manganese. An insufficiency in atleast one of these components can compromise immunocompetence of an animal. The body immune framework is made of two branches: the innate or non-specific of the immune framework, and the adaptive or specific framework of immunity. In this review paper, an effort has been established to scrutinize the effects of minerals supplement in the rumen metabolism and their individual or joined effects on body immune processes in different species of animals.
... 167 Food, drinking water, and Cu-containing supplements are the main sources of Cu toxicity in humans. 168 The main factors which can input the toxicity of high Cu to humans include season (Cu concentration is higher in greener portions), high Cu feed additives from livestock, soil quality, geography, water source, aquatic products, plants, use of fertilizers, and food processing methods, such as organ meat (liver), seafood (oysters), cocoa products, nuts (particularly cashew), and seeds. 168 In addition to food, drinking water can be another major source of Cu for humans. ...
... 168 The main factors which can input the toxicity of high Cu to humans include season (Cu concentration is higher in greener portions), high Cu feed additives from livestock, soil quality, geography, water source, aquatic products, plants, use of fertilizers, and food processing methods, such as organ meat (liver), seafood (oysters), cocoa products, nuts (particularly cashew), and seeds. 168 In addition to food, drinking water can be another major source of Cu for humans. Atmospheric dust, plant decay, and volcanic eruptions in natural activities and thermal power generation, garbage incineration, and agricultural sewage in man-made activities all lead to Cu entering the water cycle. ...
... 171 When the ingested Cu concentration continues to increase, direct stimulation of the hypothalamic vomit center triggers vomiting. 168 Another main example of chronic Cu toxicity is Wilson's disease (an autosomic recessive disorder characterized by a mutation in Cu transporter ATP7B) in humans, 172 that is, excessive accumulation of Cu in the liver, kidney, brain, and cornea will lead to Wilson's disease. Its early onset is characterized by hepatic symptoms such as lethargy, abdominal pain, hepatomegaly, and jaundice; it will evolve into chronic hepatitis, cirrhosis, and even liver failure when it develops for a long time. ...
Article
The extensive use of high-concentration copper (Cu) in feed additives, fertilizers, pesticides, and nanoparticles (NPs) inevitably causes significant pollution in the ecological environment. This type of chain pollution begins with animal husbandry: first, Cu accumulation in animals poisons them; second, high Cu enters the soil and water sources with the feces and urine to cause toxicity, which may further lead to crop and plant pollution; third, this process ultimately endangers human health through consumption of livestock products, aquatic foods, plants, and even drinking water. High Cu potentially alters the antibiotic resistance of soil and water sources and further aggravates human disease risks. Thus, it is necessary to formulate reasonable Cu emission regulations because the benefits of Cu for livestock and plants cannot be ignored. The present review evaluates the potential hazards and benefits of high Cu in livestock, the environment, the plant industry, and human health. We also discuss aspects related to bacterial and fungal resistance and homeostasis and perspectives on the application of Cu-NPs and microbial high-Cu removal technology to reduce the spread of toxicity risks to humans.
... In a systematic review on possible biomarkers of copper status, Harvey et al. (2009) stated that no conclusions can be drawn on the usefulness of erythrocyte and platelet copper; leucocyte SOD; erythrocyte, platelet and plasma glutathione peroxidase; platelet and leucocyte cytochrome c oxidase; total glutathione; and urinary pyridinoline. There was a lack of data for novel biomarkers such as CCS (copper chaperone for SOD) (Harvey et al., 2009;de Romana et al., 2011), and peptidyl glycine αamidating monooxygenase activity (Harvey et al., 2009;Bousquet-Moore et al., 2010) as biomarkers of copper status. More recently it has been suggested that CCS mRNA may be related to copper status (Araya et al., 2014), but more work is needed to test if it can be a biomarker in the general population. ...
... Factors such as season (copper concentration is higher in greener portions), soil quality (Ginocchio et al., 2002;Chaignon et al., 2003), geography, water source and use of fertilisers influence the copper content in food. Rich dietary sources of copper are liver, some seafood (oysters), cocoa products, nuts (particularly cashew) and seeds (de Romana et al., 2011). ...
... If the copper content is higher (> 1-2 mg/L), water may account for up to 50 % of total intake. In infants, contribution of water to daily copper intake may be higher because they consume proportionally more water than adults (de Romana et al., 2011). ...
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Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for copper. Owing to the absence of appropriate biomarkers of copper status and the limitations of available balance studies, the Panel was unable to derive Average Requirements (ARs) and Population Reference Intakes (PRIs). Hence, Adequate Intakes (AIs) were defined based on mean observed intakes in several European Union (EU) countries, given that there is no evidence of overt copper deficiency in the European population. Data from balance studies were used as supportive evidence. For adults, AIs of 1.6 mg/day for men and 1.3 mg/day for women are proposed. For children, AIs are 0.7 mg/day for children aged 1 to < 3 years, 1 mg/day for children aged 3 to < 10 years, and 1.3 and 1.1 mg/day for boys and girls aged 10 to < 18 years, respectively. For infants aged 7–11 months, based on mean observed intakes in four EU countries, an AI of 0.4 mg/day is proposed, which is supported by upwards extrapolation of estimated copper intake in exclusively breast-fed infants. For pregnant women, an increment of 0.2 mg/day is estimated to cover the amount of copper deposited in the fetus and the placenta over the course of pregnancy and in anticipation of the needs for lactation, and for lactating women the same increment is estimated to cover the amount of copper secreted with breast milk. Thus, for pregnant and lactating women, the Panel derived an AI of 1.5 mg/day.
... Offal (liver), wheat germ and bran, oatmeal, nuts, some seafood (oyster), cocoa, and sunflower seeds are the food products rich in copper. Sometimes, tap water may be considered a rich source of copper, especially when fittings are made of copper alloys [62,63]. However, low consumption of the aforementioned products leads to an insignificant overall copper intake. ...
... The results of the present study are in full agreement with the European and Polish data, as cereals provided the highest amounts of copper in the daily diet, followed by vegetables, meat and fruits. In addition, it was revealed that the contribution of products based on tap water (water and beverages) to the daily copper intake was very low-2.1% and 2.9% among women and men, respectively, which confirms the estimation of de Romana and coworkers [63] that foods account for over 90% of copper intake in adults when the concentration of this metal in water is low (<0.1 mg/L). ...
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Food is a major source of minerals for humans. The main objective of this study was to determine the intake level of 10 essential macro-(Na, K, Ca, and Mg) and trace elements (Cu, Zn, Mn, Fe, Cr, and Se) with major food groups among young adults. Dietary intake of elements was evaluated using the 24-h dietary recall technique in combination with F-AAS and ICP-OES methods. A very high intake of sodium and a very low intake of calcium, combined with inappropriate sodium/potassium ratio, may be harmful to the health of the population. Dietary intake of trace elements was within the range of reference values in the subjects, with cereals being the major source of a majority of those elements, while meat (38% for Na), vegetables (25% for K), and milk products (75% for Ca) were the main contributors to the daily dietary intake of macroelements. PCA revealed several visible trends in the datasetAmong men, the intake of Zn, Cr Na and K was significantly correlated with the consumption of meat and vegetables, whereas Mg, Se, Fe and Cu with cereals and water and beverages. Among women, the intake of Mg was significantly correlated with the consumption of meat and vegetables.
... Experimental and clinical studies have demonstrated that inflammatory cytokines disturb trace element homeostasis, leading to elevated copper-to-zinc ratios in some disease conditions [15]. Wisniewska et al. [16] reported elevated copper-to-zinc ratios in neonates with early congenital infections, and also observed that deficiencies of these micronutrients impaired the immune defense and made patients more susceptible to infectious diseases [17][18][19]. These disturbances in micronutrients in response to inflammation may be contributing factors to a vicious cycle of impaired immune defense and higher risk of infection in susceptible individuals [16]. ...
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Sickle cell disease (SCD) is an inherited disorder and a major health challenge in Nigeria. Micronutrient deficiencies often associated with the disorder may cause inflammation and abnormal metabolism in the body. The copper-to-zinc ratio is a more relevant diagnostic measure than the concentration of either metal alone in clinical practice. This study seeks to evaluate serum levels of c-reactive protein (CRP), copper, zinc and the copper-to-zinc ratio, and to correlate the latter with CRP in adult subjects with SCD. Serum copper, zinc, CRP and plasma fibrinogen were assayed in 100 confirmed SCD patients in steady clinical state and 100 age- and sex-matched subjects with normal hemoglobin. Serum copper and zinc were assayed by the colorimetric method using reagents supplied by Centronic, Germany, while CRP and fibrinogen were assayed using reagents supplied by Sigma (St. Louis, MO, USA) and Anogen (Ontario, Canada), respectively. The copper-to-zinc ratio was calculated from serum levels of copper and zinc. The measured parameters were compared between the groups using the Students t-test, and the Pearson correlation coefficient was used to relate CRP with the other parameters. Serum copper, CRP, fibrinogen and the copper-to-zinc ratio were significantly higher (p < 0.001), while zinc level was lower in SCD patients than in controls. Serum CRP concentration correlated with copper (r = 0.10; p < 0.02), zinc (r = −0.199; p < 0.05) and the copper-to-zinc ratio (r = 0.312; p < 0.002), but the correlation between CRP and fibrinogen was not significant. Inflammation may modulate copper and zinc homeostasis, and the copper-to-zinc ratio may be used as a marker of nutritional deficiency and inflammation in SCD patients.
... Even though the biocompatibility of 5 wt% copper with stainless steel is within the allowable range, there are still concerns about excessive dissolution in the oral cavity in the long term. The intake of excessive copper leads to severe liver damage (cirrhosis), owing to copper-induced oxidative damage in the liver and other tissues [27]. Therefore, in this study, we mainly investigated the antibacterial and mechanical properties of forged 304 Metals 2021, 11, 43 3 of 8 stainless steel by adding a low copper content (0.18, 0.54, 1.05, 1.80, and 2.05 wt%). ...
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The aim of this study was to investigate the effect of incorporating low copper (0, 0.5, 1, 1.5, and 2 wt.%) additions into as-forged AISI 304 stainless steel (304SS). The microstructures and mechanical properties of the steel were examined using scanning electron microscopy and a universal testing machine. The antibacterial properties of the Cu-bearing 304SS specimens were investigated using Escherichia coli. Each specimen was soaked in artificial saliva to detect the release of copper ions through inductively coupled plasma atomic emission spectrometry. The addition of copper had no significant effect on the microstructure of the as-forged Cu-bearing 304SS, but it slightly increased its maximum tensile strength. The antibacterial rate of the as-cast and as-forged 304SS with 2 wt.% Cu was over 80%, which corresponded to an increase in the release of copper ions. This study demonstrates that low-Cu-content stainless steel can reduce bacteria and can be a suitable material for the oral environment because of the low release of Cu ions.
... Although copper plays an essential role in the development of healthy nerves and other physiological functions in the CNS 22 , the accumulation of excessive Cu 2+ amounts can lead to neuroinflammatory injury 23,24 . WD results from copper accumulation in the liver and brain caused by mutations in ATP7B, encoding a copper transporter. ...
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Wilson’s disease (WD) is an inherited disorder characterized by excessive accumulation of copper in the body, particularly in the liver and brain. In the central nervous system (CNS), extracellular copper accumulation triggers pathological microglial activation and subsequent neurotoxicity. Growing evidence suggests that levels of inflammatory cytokines are elevated in the brain of murine WD models. However, the mechanisms associated with copper deposition to neuroinflammation have not been completely elucidated. In this study, we investigated how the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome contributes to copper-mediated neuroinflammation in an animal model of WD. Elevated levels of interleukin-1β, interleukin-18, interleukin-6, and tumor necrosis factor-α were observed in the sera of WD patients and toxic milk (TX) mice. The protein levels of inflammasome adaptor molecule apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), cleaved caspase-1, and interleukin-1β were upregulated in the brain regions of the TX mice. The NLRP3 inflammasome was activated in the TX mice brains. Furthermore, the activation of NLRP3 inflammasome was noted in primary microglia treated with CuCl 2 , accompanied by the increased levels of cleaved caspase-1, ASC, and interleukin-1β. Blocking NLRP3 inflammasome activation with siNlrp3 or MCC950 reduced interleukin-1β and interleukin-18 production, thereby effectively mitigating cognitive decline, locomotor behavior impairment, and neurodegeneration in TX mice. Overall, our study demonstrates the contribution of copper overload-mediated activation of NLRP3 inflammasome to progressive neuropathology in the CNS of a murine model of WD. Therefore, blockade of the NLRP3 inflammasome activation could be a potential therapeutic strategy for WD.
... Copper acts as a co-enzyme of lysine oxidase in the formation of connective tissue, particularly collagen and elastin. It is also involved in the metabolism of tyrosine, allowing this amino acid to play its role in the formation of thyroid hormones and in the pigmentation of the skin 46,47 . ...
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Abstract: The excessive use of plant organs such as bark, trunk and especially roots often leads to their disappearance. The overall objective of this study is to contribute to the valorization of Griffonia simplicifolia seeds from Togolese flora in agro-food and phytomedicine with biodiversity conservation. Specifically, this consists analyzing the phytochemical composition of the seeds, determining their mineral composition; and identifying some essential amino acids available in these seeds. The results obtained show that the Soxhlet extraction of the seeds’ powder with hydro-methanolic mixture (50%-50%: V/V) gave a yield of total extracts of 30.72 ± 1, 45%. Phytochemical screening of the total extracts by staining and precipitation tests revealed that alkaloids, flavonoids, tannins, saponins and total phenols are the major chemical groups contained in the extract. Flame atomic absorption spectroscopy assay has proved in the seeds the presence of minerals such as: Ca, P, K, Na, Mg, Fe, Zn, Cu, and Mn, with varying contents. Paper chromatography analysis shows that the seeds would probably contain amino acids such as: Ile, Trp, Phe and Leu. However, the analysis did not clearly identify the presence of other amino acids such as: Ala, Arg, Lys and Cys. In conclusion, the seeds of Griffonia simplicifolia have a significant nutritional potential and contain phytoconstituents with interesting pharmacological properties to promote its use in agri-food and phytomedicine in Togo. However, other studies on toxicity and anti-nutritional substances of the seeds are important before incorporation of these seeds into human beings’ diet. Keywords: Griffonia simplicifolia seeds, phytoconstituents, agri-food, phytomedicine
... Resveratrol is a plant polyphenol found in skin of red grapes and berries which has been extensively researched for its antioxidant properties [103]. Metallic copper, likewise, has been widely tested in pre-clinical studies for its potential health benefits [104]. We have discovered that when Resveratrol and Copper are combined, a remarkable reaction is triggered [71,99,101]. ...
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It is estimated that 10–50 DNA double-strand breaks (DSBs) occur in a nucleated human cell per cell cycle. We reviewed the present state of knowledge and hypothesized that the currently accepted mechanisms cannot explain such high frequency of DSBs occurring daily under normal physiological conditions. We propose an alternative model that implicates illegitimate genomic integration into healthy cells of cell-free chromatin (cfCh) particles released from the billions of cells that die in the body every day. Repeated genomic integration of cfCh may have catastrophic consequences for the cell, such as DSBs, their faulty repair by nonhomologous end joining (NHEJ) followed by apoptosis with release of more cfCh which would integrate into genomes of surrounding cells. This can creates a vicious cycle of cfCh integration, DSBs, NHEJ, and more apoptosis, thereby providing a potential explanation as to why so many billions of cells die in the body on a daily basis. We also recount the recent observation that cfCh integration and the resulting DSBs activate inflammatory cytokines. This leads us to propose that concurrent DSBs and induction of inflammation occurring throughout life may be the underlying cause of ageing, degenerative disorders, and cancer. Finally, we discuss the prospect that agents that can inactivate/degrade cfCh may hold the key to making healthy ageing a realizable goal.
... As a result of the researches, it was found that the amount of copper that should be taken daily should be 1 milligram. [7][8][9] ...
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Major depressive disorder (MDD) is a long-term mood disorder that occurs in an individual's mood. It is a disease that is mostly encountered in the adolescence period of living things, but it can also occur in other life stages. Social environment or genetic factors can be effective in the emergence of depression. The person constantly feels sad and tired, changes in eating habits, not being able to enjoy the work done, loss of concentration, and this process may result in suicide. MDD is medically treatable, but relapses occur in most individuals. Copper mineral, which plays a role in the strengthening of the skeletal-muscular system and the regeneration of tissues, is the most abundant mineral in the tissues after zinc and iron and is taken into the body through diet. It is known that in cases where copper homeostasis is not provided, it causes the development of diseases by affecting many cellular processes. In this article, the link between depression and high copper concentration in the organism will be discussed.
... Heavy metals such that present in the wastewater can be a major environmental concern, thus can cause adverse health effect to the human if consumed in higher dosage. An excessive dosage of copper can lead to chronic effect such as Wilson disease, liver damage, and insomnia [4][5] as it only needed in trace amounts. Exceeding amount of zinc could affect several human body systemic systems such as IOP Publishing doi: 10.1088/1757-899X/1053/1/012084 2 neurology, respiratory and gastrointestinal system [6]. ...
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Plating industry wastewater is one of the processes that may contain various types of heavy metals. The most common heavy metals that mostly found are copper, nickel, cadmium, chromium, silver, zinc, and lead. In this study, three types of metals which are copper, zinc and chromium trivalent were removed using hydroxide precipitation and sulphide precipitation. Both performances of the method were observed and compared. A jar test was used to determine the optimum pH, coagulant dosage and precipitant dosage. The coagulant and precipitant used in this experiment was ferric chloride (FeCl 3 ), poly aluminium chloride (PAC), sodium hydroxide (hydroxide precipitant) and sodium sulphide (sulphide precipitation) respectively. In order to remove chromium trivalent, sodium metabisulfite was used to reduce chromium hexavalent to chromium trivalent. Based on the result, hydroxide precipitation can remove 86.61% of copper, 99.81% of zinc and 99.99% of chromium trivalent. While, for sulphide precipitation, 93.91% of copper, 99.37% of zinc and 99.99% of chromium trivalent were removed. Therefore, sulphide precipitation can remove better mixed heavy metals, thus it also produces less total suspended solid compared to hydroxide precipitation.
... 18 Copper is an essential trace element engaged in activities of several mammalian enzymes. 20 It plays an important role in erythropoiesis, collagen synthesis, and assists in iron absorption. In addition, it is part of many enzymes, such as, ceruloplasmin, cytochrome c oxidase, and lysyl oxidase. ...
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Aim: To estimate the serum levels of copper (Cu) and zinc (Zn) in oral submucous fibrosis (OSMF) patients residing in the rural area. Materials and methods: The current study included 100 participants after receiving their written consent. The participants were broadly divided into group I (OSMF patients) and group II (Control), comprised of 70 and 30 individuals, respectively. The participants in group I were further categorized into three groups based on their clinical severity into group IA, group IB, and group IC corresponding to clinical stage I, stage II, and stage III OSMF, respectively. Intravenous blood was collected under a sterile environment in the plane bulb. Serum was separated and samples were stored at −40°C until use. The samples were returned to room temperature and serum Cu and Zn levels were estimated by a calorimetric test using Dibromo-PAESA method described in the kit manufactured by Centronic GmbH. Results: There were 30 participants in group IA, 25 participants in group IB, and 15 participants in group IC. Serum Cu level was significantly increased in all OSMF patients (mean = 195.305 μg/dL) in comparison with the control group and there was an increase in serum Cu level with an increase in the disease severity. Zinc level was decreased with a mean value of 80.12 μg/dL in comparison with the control group. Besides, the value decreased with an increased disease severity. Conclusion: This study reveals that these trace elements are involved in the pathophysiology of OSMF. Serum Cu and Zn levels can be used as a diagnostic tool for the early diagnosis of OSMF. Clinical significance: Serum Cu and Zn can be used as a marker to assess the OSMF disease severity. Being an important entity in the pathogenic mechanism of OSMF, their estimation may prove to be useful to dental surgeons in planning the treatment to the patients.
... Moreover, long-term intake of Cd and Pb via the food chain threatens human health (Naushad., 2014;Zhuang et al., 2014). Although copper (Cu) and zinc (Zn) are essential for various metabolic processes, they are dangerous in excess (De Romana et al., 2011;Xu et al., 2014). A recent nationwide survey of soil contaminants in China revealed that 16.1% of the investigated sites and 19.4% of the investigated farmland soils were contaminated by heavy metal(loid)s, and that heavy metal contamination of soil is particularly serious in South China (The Ministry of Environmental Protection and The Ministry of Land and Resources., 2014). ...
Article
Pfaffia glomerata is a candidate for the remediation of heavy metal-contaminated soil, but phytoremediation efficiency requires enhancement. In this study, we evaluated how application of DA-6, EDTA, or CA affected the growth and heavy metal accumulation of P. glomerata and soil microorganisms. We found that P. glomerata removed more Cd and Zn than Pb or Cu from contaminated soil. When compared to the control, application of DA-6, CA, or CA + DA-6 increased plant biomass and increased stem Cd concentration by 1.28-, 1.20-, and 1.31-fold respectively; increased leaf Cd concentration by 1.25-, 1.28-, and 1.20-fold, respectively; and increased the total quantity of Cd extracted by 1.37-, 1.37-, and 1.38-fold, respectively. When compared to the control, application EDTA or EDTA + DA-6 significantly increased the soil available metal and Na concentrations, which harmed plant growth. Application of EDTA or EDTA + DA-6 also significantly decreased the Cd concentration in roots and stems. 16S rRNA high-throughput sequencing analysis revealed that application of EDTA or CA alone to soil significantly reduced the richness and diversity of soil bacteria, while foliar spraying of DA-6 combined with EDTA or CA slightly alleviated this reduction. EDTA or CA addition significantly changed the proportion of Actinobacteria and Proteobacteria. In addition, EDTA or CA addition caused changes in soil properties (e.g. heavy metal availability, K concentration, Na concentration, soil pH, soil CEC, and soil DOC concentration) that were associated with changes in the bacterial community. EDTA addition mainly affected the soil bacterial community by changing soil DOC concentration, the soil available Pb and Na concentration, and CA addition mainly affected the soil bacterial community by changing the soil available Ca concentration.
... The absorption of Cu occurs by the small intestine and is then transferred to the liver via the portal vein from which it is further distributed to the muscle and brain through the bloodstream (de Romaña et al., 2011). Copper transport protein 1 (CTR1) is essential for the absorption of Cu via the small intestine, making it clear that CTR1 is required for Cu to be bioavailable (Nose et al., 2006). ...
Article
Mining in Butte, Montana has been ongoing since the mid-19th century. The US Environmental Protection Agency (EPA) added the Butte Area to the National Priority List in 1983, designating it a Superfund site. Butte is currently part of the largest EPA Superfund site in the United States. The EPA lists arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg) as metal contaminants of concern for residents living in proximity to the Butte Area Superfund site. However, very limited human biomonitoring has been conducted in Butte and studies that have been published focus on Pb and, to a lesser extent, As. No synergistic, antagonistic, or additive studies have been conducted, even though it is widely accepted that the exposure in Butte is a metal mixture scenario, rather than single element exposure. Metals that are trace micronutrients, such as copper (Cu), manganese (Mn), and zinc (Zn) have been largely unrecognized as possibly having negative health effects on residents of Butte, despite the fact the metals have been historically released into the soil, water, and air through active blasting and crushing of ore and are known to be potential neurotoxins. This study aims to gather data on metal distribution in soil and dust samples from a neighborhood near active mining operations, determine the bioavailability of the metals present, extract and quantify proteins and inflammatory markers from meconium samples, and investigate metal mixture interactions in human bronchial epithelial cells (BEAS-2B) and human embryonic kidney cells (HEK-293). A physiologicalbased extraction test (PBET), inductively coupled plasma mass spectrometry (ICP-MS), and inductively coupled plasma optical emission spectrometry (ICP-OES) were employed to assess metal distribution and bioavailability. To determine a link between metal exposure and possible health effects, inflammatory markers were measured by enzyme-linked immunoassays (ELISA), and metal-specific proteins were quantified by western blot assays. Metal distribution results showed that As, Mn, and Pb levels were highest in the soil samples, whereas levels of the Cd, Cu, and Zn were highest in the dust samples. The bioavailability of the metals was determined to be highest in the stomach phase for the dust samples and highest in the intestinal phase for the soil samples. Furthermore, expression of the mammalian proteins and cytokines of interest was affected differently by exposure to metal mixtures compared to single metal exposures.
... de Romaña et al., 2011 Increased shrimp mortality from zinc sulfate deposition. Lin et al., 2013 Trace mineral elements ...
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Using structured surveys in 2008 and 2016, change in disease burden and use of chemical treatments in Bangladesh shrimp farm management was examined. Overall, disease burden had increased in all farms and was more polarized, with a fewer number of individual infectious diseases responsible for most disease in ponds. Farmers also reported physical deformities, nutritional deficiencies, and unknown diseases further indicating poor health of their stock. To combat the threat, more chemical treatments were used (5.2 treatments per farm in 2008 versus 28.8 in 2016), resulting in an average increase of 424% in the number of active substances entering shrimp ponds. Although there was a modest reduction in the use of antimicrobials, shrimp was being exposed to a wider range of chemicals during rearing. The subsequent concern for the environment, animal and human health demands further research to identify potential risks from residues of chemical products.
... Acute infections alter metabolism, while deficiencies increase the risks of infection. While acute infections cause an increase in serum copper in the context of an acute phase response [70], they cause a decrease in serum zinc due to its redistribution in the liver and other tissues [68]. Physiological conditions, such as age and sex, as well as malabsorption, inflammatory condition, and genetics, significantly influence the concentrations of both trace elements [71]. ...
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Cystic fibrosis (CF) patients require a stable and sufficient supply of micronutrients. Since copper is an essential micronutrient for human development, a cross-sectional study was carried out to investigate the serum copper levels, serum copper/zinc (Cu/Zn) ratios, and their relationship with nutritional indicators in a group of CF patients. Anthropometric, biochemical, and dietary measurements, an abdominal ultrasound, and respiratory and pancreatic tests were conducted. Seventeen CF patients were studied (10 females, 59%), 76.5% of whom were ∆F580. Their mean serum copper (113 ± 23 µg/dL) was normal, and there was only one teenager with hypocupremia (6%) and two children with hypercupremia (18%). A significant association between serum copper and zinc levels was discovered. The Cu/Zn ratio was higher than 1.00 for 94% of patients, which is an indicator of an inflammation status. There was no significant correlation between the serum copper concentrations and respiratory and pancreatic function, respiratory colonization, and the results of the abdominal ultrasound. Linear regression analysis showed that serum copper had a positive association with both the Z-score body mass index (BMI) and mean bone conduction speed (BCS). Therefore, since 94% of CF patients had a Cu/Zn ratio > 1.00, this factor must alert us to consider the risk of zinc deficiency and high inflammatory response. The measurement of serum zinc alone does not show one's zinc status. However, the Cu/Zn ratio may be an indicator of zinc deficiency and the inflammatory status of CF patients.
... Copper is a crucial element for humans to maintain their biological processes, but an excessive amount in the human diet might be toxic and may introduce several adverse effects including kidney damage and liver dysfunction (de Romana et al. 2011). The highest and lowest amount of Cu was found in pond-cultured (1.20 mg/kg) and wild (0.09 mg/kg) tilapia, respectively. ...
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The present study was conducted to determine the variations of heavy metal (Cu, Pb, Ni, Cr, Cd, and Zn) bioaccumulation in edible muscles among the wild, pond-, gher- and cage-cultured tilapia, followed by risk assessment in humans caused by consumption of the contaminated fish. A total of 120 fishes from four different aquatic environments were collected, and the heavy metal levels were analyzed using an atomic absorption spectrophotometer (AAS). The result found the highest Zn concentration in all tilapia samples; however, the Ni was below the detection limit. The average concentrations of metals were found as Zn > Pb > Cr > Cu in wild tilapia, Zn > Pb > Cr > Cu > Cd in pond-cultured tilapia, Zn > Pb > Cr > Cd in gher-cultured tilapia, and Zn > Cd > Cr > Pb > Cu in cage-cultured tilapia. The estimated daily intake (EDI) value was lower than the maximum tolerable daily intake value, and target hazard quotient (THQ) and hazard index (HI) for adults, adolescent, and children was < 1 for wild and cultured tilapia, indicating that tilapia is safe for human consumption. However, high HI of Pb and Cd might be alarming and need further investigation in the near future.
... Copper is a crucial element for humans to maintain their biological processes, but an excessive amount in the human diet might be toxic and may introduce several adverse effects including kidney damage and liver dysfunction (de Romana et al. 2011). The highest and lowest amount of Cu was found in pond-cultured (1.20 mg/kg) and wild (0.09 mg/kg) tilapia, respectively. ...
Article
The present study was conducted to determine the variations of heavy metal (Cu, Pb, Ni, Cr, Cd, and Zn) bioaccumulation in edible muscles among the wild, pond-, gher-and cage-cultured tilapia, followed by risk assessment in humans caused by consumption of the contaminated fish. A total of 120 fishes from four different aquatic environments were collected, and the heavy metal levels were analyzed using an atomic absorption spectrophotometer (AAS). The result found the highest Zn concentration in all tilapia samples; however, the Ni was below the detection limit. The average concentrations of metals were found as Zn > Pb > Cr > Cu in wild tilapia, Zn > Pb > Cr > Cu > Cd in pond-cultured tilapia, Zn > Pb > Cr > Cd in gher-cultured tilapia, and Zn > Cd > Cr > Pb > Cu in cage-cultured tilapia. The estimated daily intake (EDI) value was lower than the maximum tolerable daily intake value, and target hazard quotient (THQ) and hazard index (HI) for adults, adolescent, and children was < 1 for wild and cultured tilapia, indicating that tilapia is safe for human consumption. However, high HI of Pb and Cd might be alarming and need further investigation in the near future.
... Following the development of glomerular endothelial atherosclerosis, the kidney filtration barrier is damaged. Inevitably, proteinuria resulted [10,[28][29][30]. ...
Article
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Background & objective Chronic kidney disease (CKD) is a common condition in worldwide with underlying causes. The role of trace elements such as copper and zinc in CKD is uncertain. We aimed to examine the relationship of serum copper and zinc with kidney function status and explore its possible effect modifiers in the general population. Methods Data from 5353 National Health and Nutrition Examination Survey (NHANES) participants from 2011 to 2016 were analyzed for the role of trace elements in the age range 18 to 80 years. The kidney outcomes were reduced estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² and increased urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g. Results Findings showed a significant positive association between serum copper and urinary ACR (OR = 1.04, 95% CI = 1.00–1.07). Serum copper levels of 18.0 μmol/L (median) or higher (reference level <18.0 μmol/L) were significantly associated with increased urinary ACR (OR = 1.67, 95% CI = 1.21–2.31) after adjusting for confounding factors. In contrast, there was a significant inverse association between serum zinc and reduced eGFR (OR = 0.89,95% CI = 0.81–0.99). Where serum zinc level was greater than 12.3 μmol/L (median), the prevalence of reduced eGFR was lower (OR = 0.65, 95% CI = 0.16–0.60). In addition, a stratified analysis based on various risk factors found that in those individuals with serum albumin greater than 43 g/L or systolic blood pressure greater than 120 mmHg, positive correlations between serum copper and risk of increased urinary ACR was more significant. Conclusions Our findings suggest that the reference levels of serum copper and zinc levels in healthy individuals may be different from current understanding. If further studies substantiate the same, the results will be a useful guide for designing future clinical trials and nutritional guidelines.
... In the human body, copper is taken mainly through food and water [6,7]. The waters with a slightly acidic pH have a higher content of this microelement [8]. The Cu (II) ions are excellent catalysts in electron transfer reactions in the organisms possessing a high redox activity [9]. ...
Article
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A new cyclic voltammetric method has been developed for the determination of Cu(II) in the presence of Fe(III) in tap and surface water samples using complexing properties of 5,5'-diphenylimidazolidine-2,4-dione derivative. In acetate buffer solution (0.1 mol L-1 ; pH 5.25 ± 0.01) containing minimum tenfold excess of imidazolidine derivative, copper metal ion was determined as complex compound following redox process into the working hanging mercury drop electrode (HMDE) versus Ag/AgCl, 3 mol L-1 KCl using as a reference electrode. Limits of detection as low as 0.0415 mg L-1 Cu(II) was achieved. The interfering effect of various cations as K(I), Na(I), Mg(II), Ca(II), Al(III), Zn(II), Fe(II), Fe(III) and anions: Cl − , NO 3 − , SO 4 2− , PO 4 3− , most common in surface and tap water samples, were also assessed.
... To be exact, conditions associated with increased inflammatory and/or deficient nutrition may be signaled by decreased Zn [105] and/or increased Cu [20], leading to an altered Cu/Zn ratio [106]. Therefore, in patients with an active disease, Cu levels could be higher than in patients in remission [107]. According to Lee et al., this association could be explained by the importance of Cu in collagen tissue repair [108]. ...
Article
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Copper is an essential micronutrient for humans. A cross-sectional and comparative study was done to assess serum Cu levels and serum copper/zinc (Cu/Zn) ratio and its association with nutritional indicators in a series of children and adolescents with chronic diseases. Anthropometric, biochemical, dietary, body composition, and bone densitometry assessments were carried out. Serum Cu and Zn were measured by atomic absorption spectrophotometry. Seventy-eight patients (55% women) participated. The mean serum Cu in the entire series and by nutritional status through body mass index (BMI) was normal. Serum Cu decreased significantly with age and was meaningfully higher in children than in adolescents. The risk of finding altered Cu levels in children and men was higher than in adolescents and women, respectively. Twenty-two per cent of patients had abnormal serum copper levels, 13 had hypercupremia, and four had hypocupremia. The Cu/Zn ratio was greater than 1.00 for 87% of the patients, which is an indicator of an inflammatory state. All patients with hypozincemia and hypocupremia had deficient Zn intake, but only 65% of the patients with hypercupremia had dietary Zn deficiency. Consequently, the Cu/Zn ratio could indicate an inflammatory state and a high risk of zinc deficiency in this specific child population.
... Due to its antioxidant properties, Cu plays an important role in the immune system maintenance and possesses antioxidant activity. This component acts as a cofactor of number of metalloenzymes such as superoxide dismutase (SOD) to achieve the decrease of reactive oxygen species [12]. ...
Article
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In an attempt to know the elemental composition of two endemic Algerian thyme species, we analyzed eleven mineral and trace elements (Br, Ca, Cr, Cu, Fe, K, Mn, Rb, Sr, V, and Zn) in Thymus algeriensis Boiss & Reut. and Thymus capitatus (L.) Hoffm. & Link. These species are commonly used in Algeria as aromatic and medicinal shrubs. The total concentrations of chemical elements were determined by EDXRF spectrometry. The instrument calibration was assessed through the analysis of certified reference material CRM–336 (Lichen) from the IAEA, Vienna, Austria. The results show that the highest concentrations of the micronutrients (Br, Cr, Cu, Mn, Sr, V, and Zn) were registered in T. algeriensis, while the maximum concentrations of Ca, Fe, and the non-essential element, Rb, were found in T. capitatus. Potassium contents were similar in the two species. The concentrations of essential chemical elements in T. algeriensis leaves were found in the following order: K > Ca > Mn > Fe > Zn > Cu > Cr. However, the order of these elements in T. capitatus was Ca > K > Fe > Zn > Mn > Cu > Cr. Principal component analysis (PCA) showed that T. algeriensis was highly associated with Br, Cr, Cu, Mn, Sr, V, and Zn, while T. capitatus was correlated with Ca, Fe, K, and Rb. Dietary element intakes through ingestion of 1 teaspoon of dry powder (~ 10 g) were estimated and compared to recommended daily intakes and permissible limits under FAO/WHO guidelines. In all cases, these estimates were below those levels. These findings can enhance the dissemination of these medicinal plants, which have medicinal and organoleptic properties, and provide an experiment-based guidance to the pharmaceutical and food industries.
... Some works have described that the elevation of the copper/zinc ratio (case of our study) is associated with the aggravation of oxidative stress, inflammation, malnutrition and immune deficiency. In the blood circulation, 95% of copper is transported by ceruloplasmin [95]. In our study, we observed a drastic drop in serum ceruloplasmin concentrations in the White SS group compared to the Black SS group. ...
Article
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The 25-hydroxyvitamin D3 (25OHD3) deficiency in chronic kidney disease (CKD) is associated with immune system dysfunction (pro-inflammatory cytokines storm) through macrophages renal infiltration, oxidative stress (OxS) damage and athero-thromboembolic risk. Conversely, cholecalciferol supplementation (25OHD-S) prevents kidney fibrosis by inhibition of vascular calcification and nephrotic apoptosis (nephrons reduction). The objective of this study was to investigate the pleiotropic effects of 25OHD-S on immunomodulation, antioxidant status and in protecting against thromboembolic events in deficiency CKD Black and White individuals living in the Southern Sahara (SS). The oral 25OHD-S was evaluated in 60,000 IU/month/36 weeks versus in 2000 IU/day/24 weeks in Black (n = 156) and White (n = 150). Total serum vitamin D was determined by liquid chromatography-tandem mass spectrometry. All biomarkers of pro-inflammatory cytokines (PIC) were assessed by ELISA tests. OxS markers were assessed by Randox kits. Homocysteine and lipoproteine (a) were evaluated by biochemical methods as biomarkers of atherothromboembolic risk. All statistical analyses were performed with Student’s t-test and one-way ANOVA. The Pearson test was used to calculate the correlation coefficient. The means will be significantly different at a level of p value < 0.05. Multiple logistic regressions were performed using Epi-info and Statview software. Vitamin D deficiency alters the PIC profile, OxS damage and atherothrombogenic biomarkers in both SS groups in the same manner; however, these disorders are more acute in Black compared to White SS individuals. The results showed that the serum 25OHD3 concentrations became normal (>75 nmol/L or >30 ng/mL) in the two groups. We have shown that the dose and duration of 25OHD-S treatment are not similar in Black SS residents compared to White SS subjects, whilst the same inhabit the south Sahara environment. It appears that a high dose intermittent over a long period (D60: 36 weeks) was more efficient in Black people; while a lower dose for a short time is sufficient (D2: 24 weeks) in their White counterparts. The oral 25OHD-S attenuates PIC overproduction and OxS damage, but does not reduce athero-thromboembolic risk, particularly in Black SS residents.
... mg/day (United States (US)) [47]. On average, the individual consumes~2 mg per day (WHO, 1996) [48], and 2-3 mg/day of Cu intake is safe and adequately prevents Cu deficiency, while ingesting >5 mg/day is deemed toxic [49]. for Cu is 0.9-1.3 ...
Article
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Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), are key regulators of differentiation and development. In the cell, transcription factors regulate the production of miRNA in response to different external stimuli. Copper (Cu) is a heavy metal and an essential micronutrient with widespread industrial applications. It is involved in a number of vital biological processes encompassing respiration, blood cell line maturation, and immune responses. In recent years, the link between deregulation of miRNAs’ functionality and the development of various pathologies as well as cardiovascular diseases (CVDs) has been extensively studied. Alzheimer’s disease (AD) is the most common cause of dementia in the elderly with a complex disease etiology, and its link with Cu abnormalities is being increasingly studied. A direct interaction between COMMD1, a regulator of the Cu pathway, and hypoxia-inducible factor (HIF) HIF-1a does exist in ischemic injury, but little information has been collected on the role of Cu in hypoxia associated with AD thus far. The current review deals with this matter in an attempt to structurally discuss the link between miRNA expression and Cu dysregulation in AD and CVDs.
... (accessed on 1 January 2022 )) and the data were log-transformed and Pareto-scaled before the PCA analysis. 27 Al, 24 Mg, 39 K, 43 Ca, 51 V, 55 Mn, 57 Fe, 59 Co, 63 Cu, 60 Ni, 66 Zn, 78 Se, 88 Sr, 95 Mo, 111 Cd, 208 Pb ...
Article
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A study was conducted to determine the effect of long-term supplementation with selenium and copper, administered at twice the level used in the standard diet of rats, on the content of selected elements in the femoral bones of healthy rats and rats with implanted LNCaP cancer cells. After an adaptation period, the animals were randomly divided into two experimental groups. The rats in the experimental group were implanted with prostate cancer cells. The rats in the control group were kept in the same conditions as those in the experimental group and fed the same diet, but without implanted cancer cells. The cancer cells (LNCaP) were intraperitoneally implanted in the amount of 1 × 106 (in PBS 0.4 mL) at the age of 90 days. The content of elements in the samples was determined by a quadrupole mass spectrometer with inductively coupled plasma ionization (ICP-MS). In the femoral bones of rats with implanted LNCaP cells, in the case of the standard diet and the copper-enriched diet, there was a marked decreasing trend in the content of the analysed elements relative to the control rats. This may indicate slow osteolysis taking place in the bone tissue. Contrasting results were obtained for the diet enriched with selenium; there was no significant reduction in the level of these elements, and there was even an increase in the concentrations of Fe and K in the bones of rats with implanted LNCaP cells. Particularly, numerous changes in the mineral composition of the bones were generated by enriching the diet with copper. The elements that most often underwent changes (losses) in the bones were cobalt, iron, manganese and molybdenum. The changes observed, most likely induced by the implantation of LNCaP cells, may indicate a disturbance of mineral homeostasis.
... The concentration of Cu in the liver is considered to be a good indicator of its reserves in the animal (Reglero et al. 2008) because the hepatocyte is crucial in the control of Cu homeostasis (De Romaña et al. 2011). However, in our study, Cu levels were deficient or marginal in both liver and kidney tissues for most of the animals. ...
Article
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To evaluate the nutritional status and the environmental exposure to toxic elements of the wild boar Sus scrofa L. (n = 20) from northwestern (NW) Russia, we determined the contents of the essential (Co, Cu, Fe, Mg, Mn, Ni, and Zn) and toxic (Cd and Pb) elements in the muscle, kidney, and liver. A second aim was to study the interactions between these elements and several antioxidants, namely, the activity of superoxide dismutase (SOD) and catalase, and the contents of glutathione (GSH), retinol, and α-tocopherol. A third aim was to assess whether the meat and offal of the wild boar are suitable for consumption or unsuitable due to the level of toxic elements. According to reference values of elements reported for domestic pigs, the wild boar from NW Russia was deficient in most of the essential elements (Co, Cu, Mn, Ni, and Zn) but had optimal values of Fe and Mg. The concentrations of Cd and Pb were lower than the values reported for pigs and wild boars living in heavily polluted areas. The correlations between antioxidants and elements could indicate that mineral balance in the body is regulated by antioxidants, among which the SOD activity, GSH, and retinol levels are the most sensitive parameters. Our assessment indicates that consumption of wild boar meat and liver, either rarely (4 times a year) or regularly (monthly), does not pose a health risk to adults and children, although wild boar kidney is not suitable for consumption.
... 51,52 In addition, ATP7B conveys excessive Cu tubule membranes and mediates the excretion of Cu into bile. 53,54 CP binding with Cu is the main carrier of Cu in serum. When CP reaches the surface of target cells, it interacts with corresponding receptors to release Cu, which is absorbed and utilized by target cells. ...
Article
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Ceruloplasmin (CP) is a multicopper oxidase and antioxidant that is mainly produced in the liver. CP not only plays a crucial role in the metabolic balance of copper and iron through its oxidase function but also exhibits antioxidant activity. In addition, CP is an acute-phase protein. In addition to being associated with aceruloplasminemia and neurodegenerative diseases such as Wilson's disease, Alzheimer's disease, and Parkinson's disease, CP also plays an important role in metabolic diseases, which are caused by metabolic disorders and vigorous metabolism, mainly including diabetes, obesity, hyperlipidemia, etc. Based on the physiological functions of CP, we provide an overview of the association of type 2 diabetes, obesity, hyperlipidemia, coronary heart disease, CP oxidative stress, inflammation, and metabolism of copper and iron. Studies have shown that metabolic diseases are closely related to systemic inflammation, oxidative stress, and disorders of copper and iron metabolism. Therefore, we conclude that CP, which can reduce the formation of free radicals in tissues, can be induced during inflammation and infection, and can correct the metabolic disorder of copper and iron, has protective and diagnostic effects on metabolic diseases.
... In addition to being an indicator of the copper-zinc metabolism of the human body, the Cu/Zn ratio is also related to inflammation, oxidative stress, and insulin resistance in patients undergoing MHD or other populations with chronic diseases. In patients with cystic fibrosis [11] and inflammatory bowel disease [37] and those undergoing peritoneal dialysis [9] and hemodialysis [8], the serum Cu/Zn ratio is regarded as an inflammatory marker and is positively correlated with CRP or other inflammatory markers. ...
Article
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Patients undergoing maintenance hemodialysis (MHD) are at risk of an imbalance of copper and zinc homeostasis. We hypothesized that there is an association between the blood copper-zinc (Cu/Zn) ratio and nutritional status in these patients. For this cross-sectional study, blood samples were collected from patients undergoing MHD at Guangzhou Red Cross Hospital in September 2019. Zinc and copper levels were measured using inductively coupled plasma mass spectrometry. The seven-point subjective global assessment (SGA), nutritional risk screening 2002 (NRS2002), and geriatric nutritional risk index (GNRI) were used to evaluate the overall nutritional status. We enrolled 144 MHD patients (men:women = 78:66), with an average age of 64.33 ± 13.39 years and a median dialysis vintage of 33.50 (16.25–57.50) months. Patients with a higher blood Cu/Zn ratio had lower levels of hemoglobin, blood zinc, serum prealbumin, albumin, and creatinine as well as low SGA and GNRI scores, but higher modified Charlson comorbidity index score, serum C-reactive protein level, interleukin-6 level, blood copper level, and NRS2002 score (all p < 0.05). After adjustment for confounding factors in multivariable models, a high blood Cu/Zn ratio was independently associated with nutritional risk defined by all nutritional parameters (SGA, NRS2002, and GNRI). Prospective studies with larger sample sizes are warranted to confirm these results.
... To be exact, conditions associated with increased inflammatory and/or deficient nutrition may be signaled by decreased Zn [105] and/or increased Cu [20], leading to an altered Cu/Zn ratio [106]. Therefore, in patients with an active disease, Cu levels could be higher than in patients in remission [107]. According to Lee et al., this association could be explained by the importance of Cu in collagen tissue repair [108]. ...
Article
Full-text available
Copper is an essential micronutrient for humans. A cross-sectional and comparative study was done to assess serum Cu levels and serum copper/zinc (Cu/Zn) ratio and its association with nu-tritional indicators in a series of children and adolescents with chronic diseases. Anthropometric, biochemical, dietary, body composition, and bone densitometry assessments were carried out. Serum Cu and Zn were measured by atomic absorption spectrophotometry. Seventy-eight patients (55% women) participated. The mean serum Cu in the entire series and by nutritional status through body mass index (BMI) was normal. Serum Cu decreased significantly with age and was meaningfully higher in children than in adolescents. The risk of finding altered Cu levels in children and men was higher than in adolescents and women, respectively. Twenty-two per cent of patients had abnormal serum copper levels, 13 had hypercupremia, and four had hypocupremia. The Cu/Zn ratio was greater than 1.00 for 87% of the patients, which is an indicator of an in-flammatory state. All patients with hypozincemia and hypocupremia had deficient Zn intake, but only 65% of the patients with hypercupremia had dietary Zn deficiency. Consequently, the Cu/Zn ratio could indicate an inflammatory state and a high risk of zinc deficiency in this specific child population.
... Copper is necessary to form hemoglobin and is a cofactor for over 30 proteins including superoxide dismutase, ceruloplasmin, lysyl oxidase, cytochrome c oxidase, tyrosinase and dopamine-β-hydroxylase (Arredondo and Núñez, 2005). During the past decade there has been increasing interest in the concept that marginal copper deficits ( López de Romaña et al., 2011) can contribute to the development and progression of cardiovascular disease and diabetes. Deficits in this nutrient during pregnancy can cause gross structural malformations in the fetus and persistent neurological and immunological abnormalities in the offspring (Uriu-Adams and Keen, 2005). ...
... This result may indicate the possible participation of Cu in inflammatory and pro-oxidant mechanisms in the pathogenesis of COVID-19 (Fernandes et al. 2020;Bo et al. 2008). Even though Cu is an essential micronutrient involved in various biological mechanisms, controlling its homeostasis is critical in maintaining the balance between absorption and distribution and biliary/urinary excretion (de Romaña et al. 2011;Peña et al. 1999). Both Cu deficiency and excess have been associated with specific clinical symptoms (Hordyjewska et al. 2014). ...
Article
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The role of micronutrient deficiency in the pathogenesis of COVID-19 has been reviewed in the literature; however, the data are limited and conflicting. This study investigated the association between the status of essential metals, vitamins, and antioxidant enzyme activities in COVID-19 patients and disease severity. We recruited 155 patients, who were grouped into four classes based on the Adults guideline for the Management of Coronavirus Disease 2019 at King Faisal Specialist & Research Centre (KFSH&RC): asymptomatic (N = 16), mild (N = 49), moderate (N = 68), and severe (N = 22). We measured serum levels of copper (Cu), zinc (Zn), selenium (Se), vitamin D3, vitamin A, vitamin E, total antioxidant capacity, and superoxide dismutase (SOD). Among the patients, 30%, 25%, 37%, and 68% were deficient in Se (< 70.08 µg/L), Zn (< 0.693 µg/mL), vitamin A (< 0.343 µg/mL), and vitamin D3 (< 20.05 µg/L), respectively, and SOD activity was low. Among the patients, 28% had elevated Cu levels (> 1.401 µg/mL, KFSH&RC upper reference limit). Multiple regression analysis revealed an 18% decrease in Se levels in patients with severe symptoms, which increased to 30% after adjusting the model for inflammatory markers. Regardless of inflammation, Se was independently associated with COVID-19 severity. In contrast, a 50% increase in Cu levels was associated with disease severity only after adjusting for C-reactive protein, reflecting its possible inflammatory and pro-oxidant role in COVID-19 pathogenesis. We noted an imbalance in the ratio between Cu and Zn, with ~ 83% of patients having a Cu/Zn ratio > 1, which is an indicator of inflammation. Cu-to-Zn ratio increased to 45% in patients with mild symptoms and 34%–36% in patients with moderate symptoms compared to asymptomatic patients. These relationships were only obtained when one of the laboratory parameters (lymphocyte or monocyte) or inflammatory markers (neutrophil-to-lymphocyte ratio) was included in the regression model. These findings suggest that Cu/Zn might further exacerbate inflammation in COVID-19 patients and might be synergistically associated with disease severity. A 23% decrease in vitamin A was seen in patients with severe symptoms, which disappeared after adjusting for inflammatory markers. This finding may highlight the potential role of inflammation in mediating the relationship between COVID-19 severity and vitamin A levels. Despite our patients’ low status of Zn, vitamin D3, and antioxidant enzyme (SOD), there is no evidence of their role in COVID-19 progression. Our findings reinforce that deficiency or excess of certain micronutrients plays a role in the pathogenesis of COVID-19. More studies are required to support our results.
... Adequate copper consumption promotes health benefits, correlating with good functionality of the cardiovascular system, lower blood glucose, cholesterol, and lipid levels [72], cognitive, and is not associated with arthritis or cancer, cofactor, antioxidant effects, oxidative activity, absorption, and others [73]; whereas, elevated copper intake is related to mitochondrial dysfunction [74], liver damage, and Alzheimer's disease [75]. Disturbances in the copper metabolism due to genetic conditions can result in copper deficiency (Menkes syndrome) and toxicity (Wilson's disease) [76]. ...
Article
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This study evaluates the elemental content in 4 types of canned tuna fish groups, each with 4 brands that are commercialized for human consumption in Brazil. The results are based on trace elements in canned tuna fish quantified by ICP OES and a comparison to limit levels set by the FAO/WHO. We also checked the carcinogenic risk (CR), non-carcinogenic risk (Hazard Index (HI) and Hazard Quotient (HQ)), and pollution index (PI) for the studied canned tuna samples. As and Se concentrations in all groups are above the intake values set by FAO/WHO considering specific groups. The carcinogenic risk values for arsenic (As) in groups are considerably unacceptable (≥10−4). Hazard quotients (HQ) were >1 for As in all groups, while no sample was below 1 for HI. The pollution index (PI) results show that the main canned tuna fish contaminant is aluminum, then selenium and arsenic, respectively. Only half of the samples did not present elemental contaminant levels. All studied brands of canned tuna presented elemental concentrations that could pose a health risk to human consumption, that could be from CR, HQ, HI, or PI. The contaminant levels are alarming and should raise a red flag for the intake of these products, especially a long-term one. These results urge the authorities to supervise and enforce better practices for this type of food, protecting their population from health hazards.
... This event may be due to the redistribution of the serum Se into the damaged tissues [12]. Besides, acute infections or in ammation status lead to an increase of Cu serum level concentration [13]. Interaction of this process results in an increased serum Cu/Se ratio. ...
Preprint
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Background: The relationship between strong immune response to infections and trace elements such as selenium (Se) and copper (Cu) is well documented. Furthermore, Se and Cu behave as negative and positive acute phase reactants under infectious conditions, respectively. Since SARS-CoV-2 causes systemic inflammation, this study was conducted to evaluate the association of Se and Cu serum levels with symptoms and immune response to SARS-CoV-2, and then assess the Cu/Se ratio in this matter. Methods: Blood samples and nasopharyngeal swabs were obtained from 126 SARS-CoV-2 participants with mild and severe clinical symptoms. The SARS-CoV-2 infection and immune response to the virus were confirmed by RT-PCR and anti-SARS-CoV-2 IgG, respectively. The measurement of Se and Cu serum levels were analyzed by atomic absorption spectrophotometry and colorimetric assay, respectively. Finally, data were analyzed and a P-value < 0.05 was considered statistically significant. Results: The mean Se levels were higher in patients with mild symptoms (108.73 ± 5.38 μg/L, P-value = 0.0012) and IgG non-responders (110.33 ± 3.38 μg/L, P-value < 0.001), whereas, the mean Cu was higher in participants with severe symptoms (111.055 ± 11.98 μg/dL, P-value = 0.045) and IgG responders (112 ± 9.98 μg/dL, P-value = 0.0058). The Cu/Se ratio was lower (ratio < 1) in participants with no immune responses to infection and mild symptoms versus immune responder patients with severe symptoms (P-value < 0.001). Conclusion: Our results suggest that Cu/Se ratio may be considered as a nutritional biomarker of severity and immune response in SARS-CoV-2-infected patients.
... Copper is an essential metal present in several proteins essential for biological activities in humans (de Romaña et al., 2011;Wang et al., 2021). Despite the benefits of copper in trace amounts, higher dosages are toxic to humans. ...
Thesis
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This thesis contributes to the evaluation of Cu0 + NaBH4 as a promising system for reductive dehalogenation of halogenated organic compounds (HOCs) in water. The first part of the thesis describes an investigation of Cu0 + NaBH4 in order to determine product selectivity patterns and reaction pathways in dehalogenation reactions of HOCs with the general formula CCl3–R, where R = H, F, Cl, Br, and CH3. Selectivity patterns were determined under various experimental conditions, e.g. in water matrix and with catalyst supports. When Cu0 + NaBH4 was applied to CCl3–R compounds, the formation of slowly degrading intermediates such as CH2Cl2 from CHCl3 was inevitable. Hence, optimization of Cu0 + NaBH4 in order to ensure minimization or elimination of these intermediates is discussed. The second part of the thesis explores the reactivity of Cu0 + NaBH4 with various HOC classes frequently encountered in water, soils, and sediments. A comparison was made between Cu0 + NaBH4 and the common reduction systems employing nanoscale zero-valent iron (nZVI) as a reagent and Pd catalysts + H2 as the reductant for these HOC classes. Criteria for comparison were based on the HOC’s reactivity presented as specific metal activities, yields, and the fate of the halogenated intermediates, metal costs, and metal stability in water. Application areas for Cu, nZVI, and Pd are discussed with regard to each class of HOCs. Finally, water-matrix effects on the stability of Cu catalysts were investigated for reductive dehalogenation reactions. Diese Dissertation trägt zur Untersuchung von Cu0 + NaBH4 als einem vielversprechenden System zur reduktiven Dehalogenierung von halogenierten organischen Verbindungen (HOCs) in Wasser bei. Im ersten Teil dieser Arbeit wurde das System Cu0 + NaBH4 untersucht, um die Produktselektivität und Reaktionswege während der reduktiven Dehalogenierung von HOCs mit der allgemeinen Formel CCl3–R mit R = H, F, Cl, Br und CH3 zu bestimmen. Die Selektivität wurde unter verschiedenen experimentellen Bedingungen, z.B. der Zusammensetzung der Wassermatrix und Variationen des Katalysatorträgers, bestimmt. Die Bildung von halogenierten Zwischenprodukten, unter Verwendung von Cu0 + NaBH4, ist für diese Verbindungsklassen unvermeidlich, daher wird die Optimierung des Systems zur Minimierung oder Vermeidung der Akkumulation dieser diskutiert. Im zweiten Teil der Dissertation wurde die Reaktivität des Systems Cu0 + NaBH4 mit verschiedenen HOC-Klassen untersucht, die häufig in Wässern, Böden und Sedimenten vorkommen. Zudem wurde ein Vergleich des Cu0 + NaBH4 Systems mit gebräuchlicheren Reduktionsmitteln, wie nullwertigem Eisen (nZVI) und Pd-Katalysatoren + H2, an den HOC-Klassen vorgenommen. Dabei wurden insbesondere die HOC-Reaktivität mittels der spezifischen Metall-Aktivität, die Produkt Ausbeuten, der Verbleib der halogenierten Zwischenprodukte, sowie der Katalysator- und Reduktionsmittelkosten und der Metallstabilität in Wasser diskutiert. Des Weiteren, werden Einsatzmöglichkeiten für Cu, nZVI und Pd, im Hinblick auf die verschiedenen Klassen von HOCs, diskutiert. Abschließend wurden die Auswirkungen der Wassermatrix auf die Stabilität von Cu-Katalysatoren für die reduktive Dehalogenierung untersucht.
Article
This study shows that Cu occurs predominantly as Cu-sulfides and Cu-bearing phosphates and -carbonates in organic matter (OM) colloids within smelter-impacted soils in which they are often associated with other inorganic components. Major emitters of Cu are smelters and coal-power plants, which cause severe damages to the health of soils and aquatic systems as elevated Cu concentrations are toxic for terrestrial and aquatic organisms. Toxic effects and long-term environmental fate of Cu depend among many other factors on its speciation in soil and water bodies. This study explores the role of OM colloids (defined as particles with diameters in the range of 100 to 1000 nm and with a larger proportion of organic than inorganic material) in the sequestration of Cu in contaminated soils around the Horne smelter, Rouyn Noranda, Quebec, Canada, focusing on a thin soil overlying bedrock (bedrock soil) and a forest soil. The sequestration and mobilization of Cu by OM colloids is studied using a combination of column leaching experiments, ultra-centrifugation and transmission electron microscopy (TEM). TEM analysis indicates that Cu occurs as nano-sized CuSx phases in OM colloids of the bedrock soil, and as Cu-bearing Ca-Mg-phosphates and Ca-carbonates in OM colloids of the forest soil. The nano-sized CuSx phases occur along the rim of OM colloids or are attached to silica inclusions located within OM colloids, suggesting that their in-situ formation is strongly controlled by the presence of polar groups within or on the surface of OM colloids. The proportion of Cu-bearing colloids in the soil leachates ranges from 20 to 40% of the total colloidal fraction, suggesting that OM colloids can play a significant role in the sequestration of Cu in surficial soil environments.
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This review focuses on Cu/TiO2 sequentially and Cu-TiO2 co-sputtered catalytic/photocatalytic surfaces leading to bacterial inactivation discussing their stability, synthesis, adhesion and antibacterial kinetics. The intervention of TiO2, Cu and the synergic effect of Cu and TiO2 on films prepared by a colloidal approach and other techniques is also reviewed leading to bacterial inactivation. Processes in aerobic media and anaerobic media leading to bacterial loss of viability on multidrug resistant (MDR) pathogens, Gram-negative (-) and Gram-positive(+) bacteria are described. Insight is provided for the interfacial charge transfer mechanism under solar irradiation occurring between TiO2 and Cu. surface properties of 2D TiO2/Cu and TiO2-Cu films are correlated with the bacterial inactivation kinetics observed in the dark and under light. The intervention of these antibacterial sputtered surfaces in health-care facilities leading to MRSA-isolates is described in the dark and under the actinic light. The synergic intervention of the Cu and TiO2 films leading to bacterial inactivation prepared by direct current magnetron sputtering (DCMS), pulsed direct current magnetron sputtering (DCMSP) and highly ionized pulse plasma magnetron sputtering (HIPIMS) is reported in a detailed way.
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Ensuring adequate copper supplementation in ruminants is a challenging task due to the complexity of copper metabolism in these animals. The three-way interaction between copper, molybdenum and sulphur (Cu-Mo-S) in the rumen makes ruminants, particularly cattle, very susceptible to suffering from secondary copper deficiency. Paradoxically, excessive copper storage in the liver to prevent deficiency becomes a hazard when ruminants are fed copper-supplemented diets even slightly above requirements. While cattle were traditionally thought to be relatively tolerant of copper accumulation, and reports of copper poisoning were until recently somewhat rare, in recent years an increased number of episodes/outbreaks of copper toxicity in cattle, particularly in dairy cattle, have been reported worldwide. The growing number of lethal cases reported seems to indicate that copper intoxication is spreading silently in dairy herds, urging the development of strategies to monitor herd copper status and improve farmers’ awareness of copper toxicity. In fact, monitoring studies carried out on numerous samples collected from culled animals in slaughterhouses and/or diagnostic laboratories have demonstrated that large numbers of animals have hepatic copper concentrations well above adequate levels in many different countries. These trends are undoubtedly due to copper supplementation aimed at preventing copper deficiency, as dietary copper intake from pasture alone is unlikely to cause such high levels of accumulation in liver tissue. The reasons behind the copper overfeeding in cattle are related both to a poor understanding of copper metabolism and the theory of “if adding a little produces a response, then adding a lot will produce a better response”. Contrary to most trace elements, copper in ruminants has narrow margins of safety, which must also be formulated considering the concentrations of copper antagonists in the diet. This review paper aims to provide nutritionists/veterinary practitioners with the key points about copper metabolism in cattle to guarantee an adequate copper supply while preventing excessive hepatic copper loading, which requires à la carte copper supplementation for each herd.
Article
Berberine, a traditional Chinese medicine, was found to exhibit anticoccidial activity. However, its mechanism is unclear. Trace metals such as copper and zinc are extremely low (less than 0.01% of the total weight of the body) but play a vital role in organisms. In the present study, we investigated the effect of berberine on copper and zinc levels in chickens infected with Eimeria tenella. Firstly, our data confirmed that infected chickens with E. tenella exhibited classic impairment on the 8th day of post infection, such as weight loss and increased feed conversion. Further study showed that E. tenella infection decreased the contents of copper and zinc in the liver and serum of chickens. Berberine was similar to amprolium and significantly improved the pathogenic conditions. Berberine could restore copper and zinc imbalance caused by E. tenella in chickens to a large extent. Studies on the development of cecum lesions demonstrated that the protective effect of berberine on the intestinal cecum was similar to that of the Cu/Zn mixture. Additionally, the mRNA expression of several metal transport related genes of the chick small intestine, including zinc transporter 1, copper transporter 1 and divalent metal ion transporter 1, was elevated by the treatment with berberine. Taken together, we speculate that the anticoccidial activity of berberine may be related to the maintenance of certain metals (Cu/Zn) homeostasis by affecting mRNA expression of their transport genes. However, the mode of action of BBR on these vital metals in the chicks infected with E. tenella still needs to be further studied.
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In this study, the removal of the lead and copper (as a single and binary system) from a contaminated solution was examined in batch and continuous mode operation by the adsorption on the locally synthesized new composite adsorbent. This adsorbent was prepared from the loading of Mg/Fe Layered Double Hydroxide (in an optimum molar ratio equal to 3/1) on the low cost local adsorbent prepared from physical activation of date palm leaf base (in an optimum dose equal to 0.5 g/50 mL) and characterized by using the Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscope (SEM), Energy Dispersive Spectroscopy (EDS), X-Ray Diffraction Analysis (XRD) and Specific Surface Area (BET). Adsorption studies of the solutions were examined in batch mode through experiments replicated with different values of parameters such as contact time, agitation speed, pH, initial concentrations of contaminant and adsorbent dosages; the optimum value of they were to be (1 hr, 200 rpm, 6, 5 mg/L and 0.2 g/50 mL) respectively dependent on the higher removal efficiency obtained. While for the continuous system, the effect of magnetic field exposure distance, flow rate, pH, Pb+2 and Cu+2 initial concentration and bed height on the breakthrough curve were studied in fixed and fluidized bed continuous systems; the optimum values of these parameters were to be 15 cm, 6 L/hr, 6, 5 mg/L and 20 cm respectively. The adsorption studies of the Pb+2 and Cu+2 ions in binary systems were done by using the same optimum conditions of the single systems experiments in both systems of batch and continuous; the results showed that the lead is high affinity to adsorbent than copper. Four isotherm models were conducted and the Freundlich model gives better prediction for the adsorption processes due to its lower Sum Square Errors (3.56 for Cu+2 and 2.77 for Pb+2) and higher determination coefficient (0.991 and 0.994 for Cu+2 and Pb+2 respectively) comparing with the other four isotherm models. Both first order and second order kinetic models were applied, and it found that the lead and copper adsorption process follows the pseudo-second-order kinetics model. From this results, it can concluded that the adsorption process was a chemisorption process. For the adsorption contaminants from aqueous solution in different system, the artificial neural network were studied for the normalization (C/C◦). The mean square error was ≤ 0.0595 and the yielded correlation coefficient was ≥ 0.966 for this normalization. Adsorption efficiency prediction by the transfer functions consist of a tangent sigmoid and a linear at hidden and output layer respectively with neurons in the range (2–16) depended on adsorbent and sorbate kind. The influence of each variable was specified by the experimental data ranges indicated by the sensitivity analysis depending on the artificial neural network and founded that the exposure distance for the magnetic field was the most influential system for removing contaminants.
Thesis
A nivel global, se reconoce el pescado como una fuente importante de nutrientes para la alimentación humana. Sin embargo, su consumo puede estar expuesto a los efectos de la contaminación ambiental , donde los metales pesados son de los contaminantes de mayor importancia. En este trabajo de grado se evalúa el riesgo asociado a la ingesta de pescado Coryphaena hippurus, comúnmente conocido como dorado por metales pesados potencialmente tóxicos, arsénico (As), cadmio (Cd), cobre (Cu) y plomo (Pb). Para ello se cuantifican la concentración de estos elementos mediante la técnica de digestión ácida asistida por microondas con plasma inductivamente acoplado con Emisión óptica (MAD-ICP-OES) en muestras provenientes de supermercados y pescaderías locales de la República Dominicana. Además, se estima la ingesta semanal tolerable y la dosis de consumo máxima semanal segura para hombres y mujeres adultos. Como resultado, se obtuvo que el método desarrollado presentó una alta linealidad en las curvas de calibrado evaluadas y una veracidad aceptable según la prueba de recobrado analizada. Además, la mayoría de las concentraciones de los elementos analizados se encontraron dentro de los límites de seguridad alimentaria recomendados, sin embargo detectamos niveles significativos de cobre. Así mismo, los valores de la ingesta semanal tolerable no superaron los valores establecidos por la FAO/WHO, lo que indica que el músculo de dorado analizado en este estudio es seguro para el consumo humano. De igual forma, se recomienda dosis semanales de consumo para hombres y mujeres que varían según la procedencia de las muestras, donde el plomo es el elemento de mayor contribución por su concentración cuantificada. Palabras clave: dorado, Coryphaena, Coryphaena hippurus, metales pesados, riesgo para la salud, consumo de pescado
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This is the first report on the simple preparation of gold nanoclusters stabilized with pregabalin (PREG) as a capping and reducing agent. PREG is an active pharmaceutical ingredient of the commercially available drug "Lyrica" used to treat different diseases like epilepsy and anxiety. PREG has never been used before in the synthesis of any nanoparticles or nanoclusters. The prepared gold nanoclusters (PREG-stabilized gold nanoclusters [PREG-AuNCs]) have blue fluorescence with excitation/emission at 365/425 nm, respectively. The reaction conditions were optimized for the synthesis of the as-prepared AuNCs. Different tools were used for the characterization of the synthesized nanoclusters in terms of size and surface properties. The PREG-AuNCs were exploited as a sensitive and selective fluorescent nanosensor for Cu2+ detection. The quenching of AuNC fluorescence intensity in the presence of Cu2+ is due to the aggregation-induced fluorescence quenching mechanism. The detection limit of Cu2+ ions was found to be 1.11 × 10-7 M. The selectivity of the PREG-AuNCs was studied and proved to be excellent. The drug entrapment efficacy and in vitro drug diffusion studies along with drug release kinetics helped to understand more about the pharmaceutical approaches of PREG-AuNCs. Moreover, we think that PREG-AuNCs open new opportunities as a promising candidate material for drug delivery systems and medical applications.
Article
Aims To investigate the relationship of dietary copper intake with new-onset hypertension among Chinese adults. Methods A total of 12,245 participants who were free of hypertension at baseline from the China Health and Nutrition Survey (CHNS) were included. Dietary intake was measured by 3 consecutive 24-hour dietary recalls combined with a household food inventory. New-onset hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or diagnosed by a physician or under antihypertensive treatment during the follow-up. Results During a median follow-up of 6.1 years, 4,304 participants developed new-onset hypertension. Overall, the associations between dietary copper intake and new-onset hypertension followed a U-shape (P for nonlinearity <0.001). The risk of new-onset hypertension significantly decreased with the increment of dietary copper intake (per SD increment: HR, 0.71; 95% CI, 0.57-0.88) in participants with copper intake <1.57 mg/day, and increased with the increment of dietary copper intake (per SD increment: HR, 1.09; 95% CI: 1.07-1.12) in participants with copper intake ≥1.57 mg/day. Conclusions There was a U-shaped association between dietary copper intake and new-onset hypertension in general Chinese adults, with an inflection point at about 1.57 mg/day. Our results emphasized the importance of maintaining optimal copper intake levels for the primary prevention of hypertension.
Article
Background Excessive copper (Cu) has risky effect on insulin resistance (IR), oxidative stress and inflammation. Instead, some studies reported serum Cu to be protective for non-alcoholic fatty liver disease (NAFLD). The aim of this study was to reevaluate the evidence for a potential risky correlation of serum Cu to NAFLD in large-scale and non-institutionalized American subjects. Methods A cross-sectional study of 3211 subjects was from the National Health and Nutrition Examination Survey (NHANES). Logistic regression and cubic spline-based curve-fitting analyses were used to estimate the independent risky effect of Cu to hepatic steatosis index (HSI), US fatty liver index (USFLI) and NAFLD and their dose-effect relationship. Moreover, this association was analyzed in stratification of HOMA-IR, Metabolic syndrome (MetS) and severity of NAFLD, besides age and gender. Results The average level of serum Cu was 18.67 μmol/L and the prevalence of NAFLD was 54.53% and 32.60%, respectively defined by HSI and USFLI. Generally, the level of Cu was higher in females than males. Serum Cu was positively associated with higher HSI, USFLI index and risk of NAFLD. In fully adjusted models, compared with the lowest quartile, the risk of NAFLD increased 97% in the highest quartile of Cu. Interestingly, stratified analysis showed that the risky effect of Cu to NAFLD was more prominent in the middle-aged, females and subjects with improved status of IR (lower HOMA-IR and non-Mets) compared with their counterparts. Moreover, we further found that circulating copper was correlated to severity of NAFLD only in males. Conclusion Excess serum Cu is significantly associated with risk of NAFLD, which is prominent in females, middle-aged and subjects with improved status of IR, and seems to be related to the severity of NAFLD, additionally. It is necessary to be cautious of the toxic effect of Cu and prospective cohort and mechanism studies are needed to verify the causal effect of Cu to NAFLD.
Article
Copper (Cu) pollution in water and agricultural soil has always been a worldwide concern. This research aims to investigate the health effects of copper exposure on Caenorhabditis elegans (C. elegans) under the existing environmental quality standards (1 mg/L and 2 mg/L) via lifespan, reproduction, biological markers and transcriptome analysis. The results showed that copper of these two environmental standards shorten the lifespan of nematodes, reduced the brood size, reduced the frequency of pharyngeal pumps and prolonged defecation time as aging-related behaviors, and increased the levels of aging-related markers ROS, MDA and H2O2. There was a certain effect trend for the two exposure concentrations. Further, the possible molecular mechanism of copper-induced aging and reproductive effects on C. elegans was explored. Differential gene expression analysis was performed, and 2332 genes (567 up- and 1765 down-regulated genes) in the 1 mg/L group, 2449 DEGs (724 up- and 1725 down-regulated genes) in the 2 mg/L group in response to copper treatment. The top 20 regulated genes were vit (vit-1, vit-3, vit-4) genes, col genes (col-35, col-72, col-114, col-123, col-164, col-183, col-185), eea-1, him-18 and grl-20, which suggested that cuticle collagen synthesis and yolk expression were disrupted by copper. Analysis of KEGG pathway showed copper exposure widely affects longevity regulation pathways, thereby promoting aging. In summary, the sequencing results extensively and deeply reveal the health hazards of environmentally relevant doses of copper exposure to C. elegans, and behavioral testing verified that copper promoted aging of C. elegans.
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A new type of fluorescent chemosensor has been designed and prepared by immobilizing a bis-salicylaldehyde Schiff base on the surface of SBA-15 mesoporous silica for the sensitive determination of Cu²⁺ ions in water. The characterization of nanosensor Saloph-SBA confirmed that the bis-Schiff base was successfully anchored, and the ordered mesopore channel structure was well-maintained after surface modification. Upon the addition of Cu²⁺ ions, the fluorescence of the Saloph-SBA suspension was quenched dramatically, and a good linear relation was observed for the detection of Cu²⁺ over concentration ranging 0−2 mg/L. The nanosensor had a low detection limit of 8.4×10⁻³ mg/L for Cu²⁺. In addition, the sensing selectivity study showed that the prepared probe had a good selectivity for Cu²⁺ over other interfering cations. Considering the effective regenerative ability and applicability of the nanosensor, Saloph-SBA could potentially be used as an effective nanosensor for the sensitive detection of Cu²⁺ ions in water.
Article
An AIE-active fluorescent probe,MHTS,with good sensitivity and selectivity for the detection of Cu²⁺was synthesized from myrtenal. The fluorescence intensity ofMHTSat 542 nm indicated a good linear relationship with the concentration of Cu²⁺in the range of 0-20 μM, and the detection limit was 1.25 × 10⁻⁷M, which was far lower than the national standard of Cu²⁺in drinking water. The interference experiment showed that other metal ions show no interference on the detection of Cu²⁺. The fluorescence ofMHTSchanged from yellow to colorless under a 365 nm UV light. The detection of Cu²⁺was effective in the pH range of 3-8. Therefore, it can be used for the detection of Cu²⁺in fresh vegetables and zebrafish. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2021.
Article
In a polluted environment, metals are present as complex mixtures. As a result, organisms are exposed to different metals at the same time, which affects both metal-specific as well as overall toxicity. Detailed information about the molecular mechanisms underlying the adverse effects of combined exposures remains limited in terms of different life stages. In this study, the freshwater planarian Schmidtea mediterranea was used to investigate developmental and physiological responses associated with a combined exposure to Cu and Cd. In addition, the cellular and molecular mechanisms underlying the provoked adverse effects were studied in different exposure scenarios to 20 μM CuCl2 and 10 μM CdCl2. Mixed exposure resulted in a decline in survival, diverse non-lethal morphological changes, neuroregenerative impairments, altered behaviour and a limited repair capacity. Underlying to these effects, the cellular redox state was altered in all exposure conditions. In adult animals, this led to DNA damage and corresponding transcriptional changes in cell cycle and DNA repair genes. In regenerating animals, hydrogen and glutathione contents were altered. Overall, our results demonstrate that (1) developing organisms are more susceptible to metal exposures, and (2) the toxicity of an individual metal increases significantly in a mixed exposure scenario. These aspects have to be included in current risk assessment strategies.
Article
Copper is considered as an indispensable trace element for living organisms. However, over-exposure to Cu can lead to adverse health effects on human. In this study, CuSO4 decreased sperm concentration and motility, increased sperm malformation rate. Concurrently, testicular damage including testicular histopathological aberrations and reduction of testis relative weight were observed. Then, the mechanism underlying Cu-induced testicular toxicity was explored. According to the results, CuSO4 elevated ROS production while reducing antioxidant function. Additionally, CuSO4 induced apoptosis which was featured by MMP depolarization and up-regulated levels of cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, caspase-12, cleaved-PARP and Bax, whereas down-regulated Bcl-2 expression. Meanwhile, CuSO4 caused testis DNA damage (up-regulation of γ-H2AX protein expression) and suppressed DNA repair pathways including BER, NER, HR, MMR, together with the NHEJ repair pathways, yet did not affect MGMT. To investigate the role of oxidative stress in CuSO4-induced apoptosis and DNA damage, the antioxidant NAC was co-treated with CuSO4. NAC attenuated CuSO4-induced ROS production, inhibited apoptosis and DNA damage. Furthermore, the spermatogenesis disorder was also abolished in the co-treatment with CuSO4 and NAC group. Altogether, abovementioned results indicated that CuSO4-induced spermatogenesis disorder is related to oxidative stress-mediated DNA damage and germ cell apoptosis, impairing male reproductive function.
Article
The presence of metals in canned fish has been associated with adverse effects on human health. The aim of this study was to evaluate risk-based fish consumption limits based on the concentrations of eight essential elements and four elements of toxicological concern in sardines and tuna brands commercially available in the Latin American canned goods market. One brand of canned sardines and six of canned tuna were collected and evaluated by ICP-MS and direct mercury analysis. The Hg content was much higher than that previously observed in scientific literature. According to the calculated hazard quotients, all brands may present some risk in terms of this element, especially brand F in which levels up to 3.1 µg/g were measured. Sardine samples surpassed the maximum limits of Mn and As. Stricter quality control in retail chains and industries should be implemented in order to guarantee safe levels in fishery products.
Thesis
*Full text is available in the database* Metallic copper has been widely proved as a promising antibacterial surface. This work aims to investigate the copper corrosion phenomena mostly observed in a certain type of antibacterial efficiency test, the so-called droplet method. By performing various ex-situ metallurgical methods, chemical and morphological changes on copper surfaces were characterised, with which the copper ion content and antibacterial activity were correlated. All these findings not only help to understand the origin of the antibacterial copper ion release, but also shift the research focus back on the copper surface itself, suggesting how materials research can function in antibacterial surface design.
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Red wines contain many components such as polyphenols and ethanol that may influence mineral absorption. We report on studies in a rat model that were designed to investigate the extent to which short- and long-term intake of red wine or ethanol may influence 67Zn and 65Cu absorption in rats. Rats (n 5 96) were divided into three groups, a control group that received demineralized water, a group that received red wine diluted with water (v/v) and an ethanol group that received 6% ethanol. Half of each group was used for the short-term study; the others were used for the long-term study. After 3 d (short-term study) or 28 d (long-term study) of beverage consumption, the rats were gavaged with 2 mL of solution containing 2027 nmol 67Zn and 902 nmol 65Cu. Subsequently, 3-d urinary and fecal collections were performed and analyzed for total and isotopic Zn and Cu. In the long-term study, blood, tibia and liver were also sampled for mineral status assessment. Neither short- nor long-term intake of red wine altered 67Zn or 65Cu absorption. In contrast, long-term (but not short-term) ethanol consumption significantly increased both 67Zn and 65Cu absorption compared with the control and red wine groups. The long-term consumption of ethanol or red wine did not affect blood or tissue Zn or Cu levels. In conclusion, short- or long-term consumption of red wine did not have a negative effect on intestinal absorption or tissue levels of zinc and Cu in rats. J. Nutr. 130: 1309 -1313, 2000.
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Copper, zinc superoxide dismutase (SOD) catalyses the very rapid two-step dismutation of the toxic superoxide radical (O− 2) to molecular oxygen and hydrogen peroxide through the alternate reduction and oxidation of the active-site copper1. We report here that after refitting and further refinement of the previous 2 Å structure of SOD2, analysis of the new model and its calculated molecular surface shows an extensive surface topography of sequence-conserved residues stabilized by underlying tight packing and H-bonding. There is a single, highly complementary position for O− 2 to bind to both the Cu(II) and activity-important Arg 141 with correct geometry; two water molecules form a ghost of the superoxide in this position. The geometry and molecular surface of the active site, together with biochemical data, suggest a specific model for the enzyme mechanism.
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In a double blind, 3 × 3 factorial (volume × dose) study, 70 adult females (18–60 years of age) at four different international sites (total pooled n=269) were given 100, 150, or 200 ml of bottled drinking water with 0.4, 0.8, or 1.2 mg of copper (Cu) as the sulfate salt once each week. Two additional doses (0 and 1.6 mg Cu) were added at the 200 ml volume to determine a dose–response relationship and corroborate previously reported results. All subjects completed a questionnaire at 0, 0.25, and 1 h post-dosing that screened for positive gastrointestinal (GI) effects (nausea, vomiting, abdominal pain, and diarrhea). Nausea was the most prevalent symptom reported and was generally reported within the first 15 min (water volume, p<0.032; copper dose, p<0.0001; and water volume × copper interaction, p<0.97). As volume increased, the effect of Cu-induced nausea decreased; as Cu dose increased, the incidence of nausea increased. At 200 ml, a significant increase in reported incidence of nausea at 0.25 h occurred at 1.2 mg Cu (6 mg Cu/L), indicating a NOAEL of 0.8 mg Cu (4 mg Cu/L) for adult females. These data confirm a previously determined human acute NOAEL for Cu added to distilled water, and provide additional, controlled human data for determining safe concentrations of Cu in drinking water.
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Classic copper indicators are not sensitive and specific for detecting excess copper exposure when this is higher than customary but not markedly elevated. Serum copper and ceruloplasmin (Cp) are the most commonly used indicators to assess nutritional status of copper. The objective of this paper was to study the influence of estrogens on these indicators and others used to assess early effects of excess copper exposure in humans and the expression of a set of copper related proteins in a hepatic cellular model. For the studies in humans, 107 healthy participants (18-50 years) were allocated as follows: group 1 (n = 39), women assessed on day 7 of their hormonal cycle; group 2 (n = 34), women assessed on day 21 of their hormonal cycle, and group 3 (n = 34, comparison group), healthy men. Participants received 8 mg Cu/day (as copper sulfate) during 6 months. Serum Cp and Cu, Cu-Zn-superoxide dismutase activity, liver function indicators [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyltransferase (GGT)], and serum Fe and Zn concentrations were measured monthly. In addition, the influence of estradiol on intracellular total copper content, hctr1, dmt1 and shbg mRNA abundance and hCTR1, and DMT1 expression was measured in HepG2 cells. Serum Cu, Fe, and Zn and liver aminotransferases but not Cu-Zn-superoxide dismutase varied depending on sex. Fe nutrition indicators, GGT, and ALT activities showed significant differences between the hormonal phases. Cellular experiments showed that estradiol increased cellular Cu concentration and hCTR1 and DMT1 mRNA expression and changed these proteins expression patterns. Estradiols significantly influence the responses to copper at the whole body and the cellular levels, suggesting that they help maintaining copper availability for metabolic needs.
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The response by Brewer & Althaus to our recent review on biomarkers for Cu ⁽ ¹ ⁾ bears testimony that the subject is topical and of public, scientific and commercial interest.
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Serum or plasma copper and ceruloplasmin concentrations are the most widely used laboratory indicators to evaluate copper status. Both indicators are decreased in moderate or severe copper deficiency. The activity of several cuproenzymes is decreased in mild copper deficiency. However, their use is limited by the nonexistence of standardized assays and high interindividual variability and because some of these indicators are affected by other conditions. Recently, it was shown that the protein expression of the copper chaperone for superoxide dismutase (CCS) is increased in erythrocytes of rodents with mild copper deficiency. However, no traditional laboratory indicators have been identified as potential early markers of copper excess. It is possible that the biomarkers studied so far are not sensitive enough to detect an increase in body copper before the appearance of functional or clinical effects or that the homeostatic mechanisms are so strong that no significant changes in body copper occur with mild-to-moderate copper exposure. The identification of appropriate biomarkers for early detection of an increase in body copper represents a major challenge for further research, and the development of new approaches, such as network biology, allows us to search and propose new candidates to be studied. Recently, we found that CCS mRNA abundance in mononuclear blood cells significantly decreased after copper supplementation. The usefulness of this indicator to detect an increase in body copper should be assessed in clinical trials.
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Emetic thresholds to copper sulfate administered into the Pavlov pouch, Forrest pouch, Thiry fistulas of the jejunum and ileum, and duodenal, jejunal and ileal catheters were measured in dogs to conjecture the site of emetic action of copper sulfate. The oral emetic threshold had been measured preoperatively. In the stomach, the pyloric antrum had a high sensitivity, while the corpus had a low sensitivity to the topically applied copper sulfate. In the intestine, the sensitivity was high in the duodenum, whereas a low sensitivity was noted in the jejunum. Almost no sensitivity was observed in the ileum. Thus it would appear that the site of the emetic action of copper sulfate was the pyloric antrum and/or duodenum.
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Cellular copper metabolism and the mechanism of resistance to copper toxicity were investigated using a wild type hepatoma cell line (HAC) and a copper-resistant cell line (HAC600) that accumulates copper and has a highly elevated level of metallothionein (MT). Of the enzymes involved in reactive oxygen metabolism, only glutathionine peroxidase was elevated (3–4-fold) in resistant cells, suggestive of an increase in the cellular flux of hydrogen peroxide. A majority of the cytoplasmic copper (> 60%) was isolated from both cell lines as a GSH complex. Kinetic studies of ⁶⁷Cu uptake showed that GSH bound ⁶⁷Cu before the metal was complexed by MT. Depletion of cellular GSH with buthionine sulfoximine inhibited the incorporation of ⁶⁷Cu into MT by greater than 50%. These results support a model of copper metabolism in which the metal is complexed by GSH soon after entering the cell. The complexed metal is then transferred to MT where it is stored. This study also indicates that resistance to metal toxicity in copper-resistant hepatoma cells is due to increases in both cellular GSH and MT. Furthermore, it is suggested that elevated levels of GSH peroxidase allows cells to more efficiently accommodate an increased cellular hydrogen peroxide flux that may occur as a consequence of elevated levels of cytoplasmic copper.
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Eleven young men were confined to a metabolic research unit for 90 d to determine the effect of the level of dietary copper on absorption and retention. Cu absorption was determined by feeding the stable isotope 65Cu. Absorption and retention averaged 36.3 +/- 1.3% and 0.17 mg/d, respectively, with an adequate-Cu diet (1.68 mg/d). Absorption averaged 55.6 +/- 0.9% and retention averaged -0.316 mg/d for 6 d and 0.093 mg/d for the next 36 d of a low-Cu diet (0.785 mg/d). Absorption averaged 12.4 +/- 0.9% with a high-Cu diet (7.53 mg/d) and retention was strongly positive at first, decreasing linearly with time. The study demonstrated that Cu absorption is strongly dependent on dietary Cu level and that Cu balance can be achieved by most young men from a diet of 0.8 mg Cu/d. These results suggest that current dietary Cu recommendations may be higher than necessary. The apparent regulation of Cu absorption and endogenous losses would tend to protect humans from Cu deficiency and toxicity.
Article
It is possible, in vitro, to label albumin with copper either exclusively on the specific binding site or partly on the specific site and also on other sites by altering the pH at which the two ligands are mixed. Copper attached exclusively to the specific site is taken up more rapidly than copper attached to that site and others on albumin. The effect is proportional to the amount of copper on the specific site. Additional histidine stimulates uptake irrespective of the copper binding site on albumin. The effect is related to the histidine on position 3 of the albumin, since it is not seen when dog albumin is labeled under the same conditions. The data suggest that the cell recognizes and presumably binds the copper-albumin (CuAlb) complex but may preferentially recognize the ternary complex formed by CuAlb and histidine. We suggest that, in vivo, copper is bound mainly as the ternary complex and that the structure formed, presumably similar to that formed by a copper-histidine complex, is what is actually recognized by the cell. After binding, the albumin and histidine are released, possibly by a reduction step, and the copper is transported across the membrane. If the copper cannot be transported (as occurs when the cells are incubated at 4 degrees C), it blocks further binding of the ternary complex.
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Copper metabolismWilson's disease (WD, McKusick277900)Non-Wilsonian copper-related cirrhosis in childhood
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Patient: A 26-year-old man who had ingested 10 times the maximum dose of dietary copper supplement for 2 years. Presentation: Acute liver failure. Outcome: Emergency liver transplant with successful outcome. Conclusions: Chronic copper intoxication can cause cirrhosis resembling Wilson's disease. Dietary copper supplements should carry a clear warning.
Article
The distribution and variation of copper in our foods is illustrated in the table presented in the report. It may be useful in determining the adequacy of copper in daily diets and in planning copper restricted diets.
Article
Introduction Low serum copper concentrations are characteristic of the newborn infant * and are known to occur in nephrosis,† in sprue,7 and in the hepatolenticular degenerative disorder of Wilson.‡ In addition, Zurukzoglu-Sklavounou in Switzerland,11 Stransky in the Phillipine Islands12 and Axtrup in Sweden,13 although attaching little or no significance to the findings, have published data indicating the sporadic occurrence of hypocupremia in infants with hypochromic, microcytic anemia. On the other hand, it is generally concluded that the serum copper concentration is normal or elevated in iron deficiency anemia and data supporting this position have been reported by Axtrup,13 Brenner,14 Freudenberg,15 and by Lahey and co-workers,9 as well as by the previously cited authors.§Infants maintained on nearly exclusive milk diets are likely to develop a microcytic, hypochromic anemia typical of iron deficiency and closely resembling the anemia produced in swine by copper-deficient diets.‖
Article
Two patients with sideroblastic anemia secondary to zinc-induced copper deficiency absorbed excess zinc secondary to oral ingestion. The source of excess zinc was a zinc supplement in one case; in the other, ingested coins. In each case, the sideroblastic anemia was corrected promptly after removal of the source of excess zinc. These two cases emphasize the importance of recognizing this clinical entity, since the myelodysplastic features are completely reversible. (JAMA. 1990;264:1441-1443)
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Hypocupremia occurred in an adult with sickle cell anemia who received zinc as an antisickling agent for two years. The hypocupremia was associated with microcytosis and relative neutropenia. Administration of copper resulted in an increase in RBC size and leukocyte counts. We have since observed hypoceruloplasminemia of varying degrees in several other sickle cell anemia patients who were receiving oral zinc therapy. This complication was easily corrected by copper supplementation. (JAMA 240:2166-2168, 1978)
Article
This analysis is based on the responses of participants in the most recent Nationwide Food Consumption Survey in 1987-88. The data are descriptive of nutrient intake of a large number of Americans. The results do not provide population estimates for the United States.
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Sensitivity of the assay for Cu,Zn superoxide dismutase 3 (SOD3), the predominant form of SOD in serum, can be increased, and interferences caused by low-molecular-weight substances in the serum can be reduced by conducting the assay at pH 10 with xanthine/xanthine oxidase and acetylated cytochrome c (cyt c) as superoxide generator and detector, respectively. Serum SOD3 activity was assayed under these conditions in an experiment where weanling, male rats were fed diets for 6 weeks containing 3, 5 and 15 mg Zn/kg with dietary Cu set at 0.3, 1.5 and 5 mg Cu/kg at each level of dietary Zn. Serum SOD3 responded to changes in dietary Cu but not to changes in dietary Zn. A second experiment compared serum SOD3 activity to traditional indices of Cu status in weanling, male and female rats after they were fed diets containing, nominally, 0, 1, 1.5, 2, 2.5, 3 and 6 mg Cu/kg for 6 weeks. Serum SOD3 activity was significantly lower (P<.05) in male rats fed diets containing 0 and 1 mg Cu/kg and female rats fed diet containing 0 mg Cu/kg compared with rats fed diet containing 6 mg Cu/kg. These changes were similar to changes in liver Cu concentrations, liver cyt c oxidase (CCO) activity and plasma ceruloplasmin in males and females. Serum SOD3 activity was also strongly, positively correlated with liver Cu concentrations over the entire range of dietary Cu concentrations (R2=.942 in males, R2=.884 in females, P<.0001). Plots of serum SOD3 activity, liver Cu concentration, liver CCO activity and ceruloplasmin as functions of kidney Cu concentration all had two linear segments that intersected at similar kidney Cu concentrations (18-22 microgram/g dry kidney in males, 15-17 microgram/g dry kidney in females). These findings indicate that serum SOD3 activity is a sensitive index of Cu status.
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Copper (Cu), an essential element required as a cofactor and/or structural component of numerous metalloenzymes, is uniquely positioned as a case study for issues associated with the essential metals health risk assessment, because of its extensive database. Essential elements pose distinct challenges when establishing regulatory guidelines because too little as well as too much intake can produce adverse health consequences and the dose-response curve is roughly U-shaped. Thus, conventional health risk assessment paradigms do not apply to essential elements; the dose-response assessment needs to define an acceptable range of oral intake (AROI) which prevents deficiency by meeting nutritional requirements while avoiding toxicity due to high intakes. The conceptual framework for this type of risk assessment includes consideration of biological processes that are unique to essential elements-homeostasis, basal and normative nutritional requirements, bioavailability, and nutrient-nutrient interactions. In this paper, the Cu database on physiology, deficiency, and excess is briefly reviewed in order to establish the range of potential health hazards associated with varying levels of intake. Issues discussed include the (1) development of suitable dose-response methodologies, including appropriate dose and response metrics, for Cu; (2) categorization of severity of response and functional significance; (3) use of endpoints of similar severity and functionality for deficiency and excess in dose-response assessment; (4) development of valid biomarkers for subclinical effects, exposures and susceptibilities. Guideline values for Cu intake have been established by nutritional and toxicologic regulatory or advisory boards. Although regulators are more concerned with the potential human toxicity arising from excessive Cu intake, the preponderance of evidence suggests that deficiency is more of a public health concern than excess.
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Tetrathiomolybdate (TM), an anticopper drug, has been developed for the neurologic presentation of Wilson's disease. In animal models, lowering copper levels with TM produces antifibrotic, anti-inflammatory, antiautoimmune, and anticancer effects, thought to be due to inhibition of many cytokines that are dependent on available copper for their activity. Clinical testing has been done relatively extensively in Wilson's disease and advanced cancers, but remains in its infancy in other diseases. To review current preclinical and clinical studies done with TM, and our current knowledge of TM efficacy and toxicity. We have reviewed the last 10 years of literature on TM therapy. TM has excellent efficacy and acceptable toxicity for the initial treatment of neurologically presenting Wilson's disease. TM has excellent efficacy in animal models of fibrotic, inflammatory, autoimmune, and neoplastic diseases, as well as Alzheimer's disease models.
Article
Copper is a redox active metal that is essential for biological function. Copper is potentially toxic; thus, its homeostasis is carefully regulated through a system of protein transporters. Copper is taken up across the lumen surface of the small intestinal microvilli as cuprous ion by Ctr1. Cupric ion may also be taken up, but those processes are less well understood. Within the cell, intestinal as well as others, copper is escorted to specific compartments by metallochaperones. One, CCS, donates copper to superoxide dismutase. Another, COX17, delivers copper to additional chaperones within the mitochondria for synthesis of cytochrome c oxidase. A third chaperone, Atox1, delivers copper to the secretory pathway by docking with 2 P-type ATPases. One, ATP7A, is the protein nonfunctional in Menkes disease. This protein is required for cuproenzyme biosynthesis, and in the enterocyte it is required for copper efflux to portal blood. The second, ATP7B, predominantly expressed in liver, is required for copper metallation of ceruloplasmin and biliary copper excretion. Mutations in ATP7B lead to Wilson disease. Additional intracellular hepatic copper-binding proteins COMMD1 (copper metabolism MURR1 domain) and XIAP (X-linked inhibitor of apoptosis protein) may also be required for excretion. Other proteins involved in copper homeostasis may include metallothionein and amyloid precursor protein. Plasma protein transport of copper from the intestine to liver and in systemic circulation probably includes both albumin and alpha2-macroglobulin. Changes in the expression of copper "transporters" may be useful to monitor copper status of humans, provided a suitable cell type can be sampled.
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Hypocupremia occurred in an adult with sickle cell anemia who received zinc as an antisickling agent for two years. The hypocupremia was associated with microcytosis and relative neutropenia. Administration of copper resulted in an increase in RBC size and leukocyte counts. We have since observed hypoceruloplasminemia of varying degrees in several other sickle cell anemia patients who were receiving oral zinc therapy. This complication was easily corrected by copper supplementation.
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Aspects of metabolism of various copper proteins absorption of copper, transport of copper, excretion of copper, copper in the diet, its metabolism in pre- and postnatal life, dietary copper deficiency, Menke's and Wilson's disease, hypo- and hypercupremia, copper toxicity, interrelationships between copper and other elements and human requirements are reviewed. 879 refs. (I. Syrovy, Prague)
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The Recommended Dietary Allowances serve two basic uses: As guidelines for planning diets and food supplies and as a tool for evaluating nutritional adequacy of food consumed. Establishing standards to serve these functions is not simple. Differences in individuals in different population groups dictate allowances with relatively high margins of safety to prevent deficiencies. Even so, anomalies arise. Surveys have shown that intakes of vitamin A and protein are likely to exceed their respective allowances. On the other hand, calcium and thiamin intakes of older women and iron in teenage boys and women in the reproductive years are difficult to meet in terms of nutrient density ratios. In addition, insufficient data make it impossible to set allowances for some essential trace elements--and, other essential elements may yet be discovered. Thus the allowances are not guaranteed to represent the totality of nutritional needs.