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Risks and benefits of copper in light of new insights of copper homeostasis
... Absorption is inhibited by the presence of other minerals like zinc and iron, which can compete with copper for absorption. Additionally, certain compounds like phytates and oxalates bind to Cu 2+ in the gastrointestinal tract and inhibit absorption (11). The relative absorption has been reported to be lower in lacto-ovo-vegetarian compared to non-vegetarian diets, but as the copper content was higher in the vegetarian diet, the net absorption was higher (12). ...
... Other suggested indices of copper status include superoxide dismutase (SOD) activity, platelet copper concentration and cytochrome C oxidase activity because all of these have been shown to decline at low copper intakes. However, none of these indicators has been found suitable for the detection of marginal copper deficiency or marginal copper toxicity (11,25). Instead, animal studies have suggested that one of the copper chaperones, CCS1, might be a potential biomarker for marginal copper deficiency and toxicity (26). ...
Copper functions as a structural component in many proteins involved in energy and iron metabolism, production of neurotransmitters, formation of connective tissue and endogenous antioxidant defence. Several biochemical indices have been suggested and used to assess copper status, but none of these has been found suitable for the detection of marginal copper deficiency or marginal copper toxicity. Copper imbalances have been linked to the pathogenesis of several chronic inflammatory diseases. During the last decade, a number of meta-analyses and systematic reviews have been published shedding light on the association between copper imbalances and some of these pathologies. Most of these meta-analyses are based on case–control studies. All show that blood copper concentrations are higher in cases than in controls, but there is inconclusive evidence to change the recommendations.
... The synthesized metallic NPs have unique optical, catalytic, biological and electromagnetic properties and can be applied in different areas such as biochemistry, engineering, medicine, agriculture, electronics, biomedicine, and groundwater treatment 24-29 . Among metal NPs, Cu has attracted significant attention due to its non-toxicity, affluence, high optical sorption coefficient and low band energies, as well as use in reaction progress, semiconductor devices, solar energy conversion, gas measurement, antimicrobial materials, night light sources, emission devices and Li-ion electrodes [30][31][32][33] . ...
... All synthesized compounds were dissolved in DMSO at an initial concentration of 40,960 μg/ml and two-fold serially diluted in a 96-well microtiter. 100 μl of the microbial suspensions and 80 μl of broth culture media (Mueller-Hinton for bacteria and Sabouraud dextrose for fungi) were added to each well of the microplate containing 20 μl of diluted solution of compounds to obtain final concentrations 4096, 2048, 1024, 512, 256, 128, 64,32,16,8,4, and 2 μg/ml. The microplates were incubated at 37 °C for 24 h. ...
The physicochemical properties of materials change significantly in nanometer dimensions. Therefore, several methods have been proposed for the synthesis of nanoparticles. Plant extracts and essential oils are applied as natural and economic resources to prepare nanomaterials especially metal nanoparticles. In this project, a green, simple and efficient method has been designed for the synthesis of Cu nanoparticles using Purple cabbage extract as a reducing and stabilizing agent. They were successfully loaded onto a new Ag complex containing 1,3,5-triazine Schiff base as ligand to form Cu@Ag-CPX nanocomposite. Phytochemical contents of extract were identified by standard qualitative analyses. The chemical structure of all synthesized compounds was characterized using spectral data. In FT-IR, coordination of C=N bond of Schiff base ligand to Ag⁺ ions shifted the absorption band from 1641 to 1632 cm⁻¹. The UV–Vis spectrum of Cu@Ag-CPX nanocomposite shown the peak related to Cu nanoparticles in the region of around 251 nm. 5:7 molar ratio of Cu to Ag in Cu@Ag-CPX was determined using ICP-OES. The FESEM, TEM, and DLS techniques provided valuable insights into the morphology and size distribution of the nanocomposite, revealing the presence of rods and monodispersed particles with specific diameter ranges. These analyses of the nanocomposite displayed rods with diameters from 40 to 62 nm as well as monodispersed and uniform particles with average diameter of 45 nm, respectively. The presence of elements including carbon, nitrogen, oxygen, Cu and Ag was proved by EDX-EDS analysis. The XRD pattern of Cu@Ag-CPX shown the diffraction peaks of Cu and Ag particles at 2θ values of 10°–80°, and confirmed its crystalline nature. The inhibitory properties of the synthesized compounds were evaluated in vitro against four Gram-negative and two Gram-positive bacteria, as well as two fungal strains. The MIC, MBC and MFC values obtained from microdilution and streak plate sensitivity tests were ranged from 128 to 4096 µg ml⁻¹. While Cu nanoparticles and Ag complexes were effective against some pathogens, they were not effective against all them. However, the growth of all tested microbial strains was inhibited by Cu@Ag-CPX nanocomposite, and makes it as a new promising antimicrobial agent. Modification of nanocomposite in terms of nanoparticle and complex can improve its blocking activities.
... The suggested safe concentration in drinking water for humans varies depending on the source but tends to stabilize between 1.5 and 2 mg L −1 . Dietary reference intake: the tolerable upper limit for adult consumption of dietary copper from all sources is 10 mg/day [6,7]. ...
... The experimental adsorption data were fitted to linear forms of adsorption isotherms models. The data were calculated from selected adsorption isotherms models, using Equations (4)- (7) in Table 2 at the experimental temperature of 25 °C. ...
The study of Cu(II) from aqueous solutions using the adsorption process on synthetically modified geopolymers was performed under static conditions. Three geopolymers (based on meta-phase of Serbian clay, metaphase of German clay and metaphase of German clay plus 10% of carbon cloth) were used. The geopolymers were made by condensing a mixture of metaphases and alkali activator solution at a fixed ratio at room temperature and then at a temperature of 60 °C in a dry oven. Then, the geopolymer samples were pre-crashed to a fixed-radius size. Their properties were characterized by X-ray diffractometry (XRD), Diffuse Reflectance Infrared Fourier Transform (DRIFT) analysis and Scanning Electron Microscopy (SEM) with Energy Dispersive Spectroscopy (EDS). Adsorption experiments were carried out under batch process as a function of the dose, concentration of metal, and contact time. The uptake of Cu(II) was rapid, and it increased with increasing metal concentration. The sorption percentage decreased with increasing concentration of Cu(II). The equilibrium adsorption capacity of geopolymers was measured and extrapolated using more isotherms. The data fit very well the linear Langmuir isotherm model. The pseudo-second-order kinetic model can well describe the adsorption behavior of Cu(II) ions with geopolymers samples. These results show that used geopolymers hold great potential to remove Cu(II) from industrial wastewater.
... Cu is found in natural mineral water, and water pipes can also release some Cu into drinking water, while seafood, organ meat, cocoa products, nuts (particularly cashew), and seeds are also important sources (150). Cu is absorbed in the intestine and secreted into the portal vein circulation, where it binds to albumin, transporters, low molecular weight Cu histidine complexes, or combinations of them as Cu 2+ and is excreted into the gastrointestinal tract, either via the bile or in a non-absorbed form (151). The recommended dietary allowance for Cu increases throughout later childhood and adolescence, and is 900 μg/day in adults (152). ...
... In addition to the damage caused by oxidative stress, Cu overload can cause other adverse effects. Large doses of acute excess Cu can be fatal, whereas small doses of acute Cu excess present early with gastrointestinal reactions, such as nausea and vomiting, possibly due to stimulation of the vagus nerve (151). Other symptoms include abdominal pain, gastrointestinal hemorrhage, melena, jaundice, anorexia, severe thirst, diarrhea, and liver and kidney failure (181). ...
Background and objective:
Chronic kidney disease (CKD) is an important public health concern. With the decline of renal function, CKD patients gradually progress to end-stage kidney disease and need to undergo dialysis or kidney transplantation to maintain life, bringing a heavy economic burden to the family and society. Therefore, it is necessary to effectively prevent and delay the progression of CKD. Essential trace elements play an indispensable role in CKD, and the objective of this study is to systematically review their benefits in the disease and summarize the risks of their excess.
Methods:
The keywords "trace elements", "chronic kidney disease", "dialysis", "inflammation", and "fibrosis" and their combinations were used to search for relevant literature published in the PubMed database and Web of Science. We then summarized the role of trace element abnormalities in CKD patients in anemia, oxidative stress, inflammation, and chronic fibrosis, and the risk of their excess.
Key content and findings:
Imbalance of essential trace elements is a common complication of CKD and a risk factor for CKD progression, cardiovascular events, and death. This article reviews the effects of essential trace elements (iron, zinc, selenium, copper, iodine, and manganese) on CKD. We analyze literature and discuss the advantages and disadvantages of various essential trace elements.
Conclusions:
Research shows CKD patients have an imbalance of essential trace elements, and treatment based on these is an important direction for future exploration. A knowledge of the homeostasis of trace elements is important to improving the prognosis of CKD patients and delaying the progression of the disease.
... In contrast, a mutation in the ATP7B gene results in Wilson's disease, which causes copper accumulation and toxicity in the brain and liver as ATP7B is crucial for copper transport from the liver into bile (Czlonkowska et al., 2018;Mercer et al., 2017). Disturbances in copper homeostasis have also been observed in a variety of neurodegenerative diseases, including Alzheimer's disease (Li et al., 2012), Parkinson's disease (Bisaglia and Bubacco, 2020) and amyotrophic lateral sclerosis (Tokuda and Furukawa, 2016), as well as in patients with cardiac disease (de Romana et al., 2011). Thus, copper homeostasis is essential for human health as both deficiency and excess of copper result in significant pathology and are observed in multiple diseases. ...
Invasive fungal infections represent a significant global health problem, and present several clinical challenges, including limited treatment options, increasing rates of antifungal drug resistance and compounding comorbidities in affected patients. Metals, such as copper, iron and zinc, are critical for various biological and cellular processes across phyla. In mammals, these metals are important determinants of immune responses, but pathogenic microbes, including fungi, also require access to these metals to fuel their own growth and drive expression of major virulence traits. Therefore, host immune cells have developed strategies to either restrict access to metals to induce starvation of invading pathogens or deploy toxic concentrations within phagosomes to cause metal poisoning. In this Review, we describe the mechanisms regulating fungal scavenging and detoxification of copper, iron and zinc and the importance of these mechanisms for virulence and infection. We also outline how these metals are involved in host immune responses and the consequences of metal deficiencies or overloads on how the host controls invasive fungal infections.
... In the present study, cotton thread was chosen as the substrate material for the proposed µTAD due to its suitable properties, including high hydrophobicity and capillarity through the cotton thread lumen, which make it highly desirable for use in the construction of µTAD. 1 For the choice of the most suitable cotton thread, initially, two types of commercial cotton thread were tested with and without pretreatment using hot sodium carbonate saline: surgical cotton thread (F 1 ) and crochet cotton thread (F 2 ), along with their respective treated versions F 1 T and F 2 T. This analysis was performed in order to find out which cotton thread exhibits the best capillarity and offers the greatest color intensity for CPZ-Cu complex solution. ...
In the present work, we report the development of a novel cotton thread-based colorimetric sensor modified by carboxymethylcellulose (CMC) and cuprizone (CPZ) with smartphone detection and its application for the quantitative determination of cupric ions in water and cachaça. The cotton thread/smartphone detection-based colorimetric method is an easily affordable, low-cost technique which allows one to perform real-time and on-field determination analyses, especially with limited financial resources. The method involves the complexation of Cu(II) with CPZ, which causes a change in the coloration of the cotton thread from a shade of white to blue in the detection zone of the colorimetric sensor. The immobilization of CPZ on CMC in the cotton thread leads to the pre-concentration of Cu(II) via a complexation mechanism with colorimetric reaction. The application of the colorimetric sensor allows the quantification of copper in the range from 1 to 12 mg L-1, with a low limit of detection of 0.21 mg L-1. In addition, the recovery assays conducted in samples of water and cachaça resulted in recovery percentages ranging from 84.9% to 107%, which is indicative of a precise method. To validate the precision of the proposed colorimetric method, the values obtained from the quantification analysis were compared with those of the flame atomic absorption spectrometry and a good agreement at the 95% confidence level was obtained.
... Henceforth, the future consideration of confining metal concentrations within a physiologically tolerable range is warranted [155][156][157]. Moreover, it is imperative to devise methodologies capable of precisely modulating the concentration of trace metal elements within a confined region and specific cell types and organs, thereby circumventing any systemic repercussions subsequent to administration. ...
Trace metal elements are of vital importance for fundamental biological processes. They function in various metabolic pathways after the long evolution of living organisms. Glucose is considered to be one of the main sources of biological energy that supports biological activities, and its metabolism is tightly regulated by trace metal elements such as iron, zinc, copper, and manganese. However, there is still a lack of understanding of the regulation of glucose metabolism by trace metal elements. In particular, the underlying mechanism of action remains to be elucidated. In this review, we summarize the current concepts and progress linking trace metal elements and glucose metabolism, particularly for the trace metal elements zinc, copper, manganese, and iron.
... Copper is a micronutrient that is necessary for many biological processes that are necessary for life to continue. However, excessive amounts of it can be harmful (De Roman et al., 2011). The soil's Cu concentration ranges from 576.80 mg/kg to 3,625.60 mg/kg, which is higher than Mokgolele and Likuku's (2011) findings. ...
Radionuclides and heavy metals exist in every human environment as a result of increasing anthropogenic activities. Their pollution of soil, water, and atmosphere represents a growing environmental problem affecting food quality and human health. The samples of soil used for this study were collected from Foron Bisitchi and Mazat communities of Barkin Ladi Area of Plateau state. The samples were analyzed using Canberra Model 727/727R Lead Shield Gamma ray Spectrometer with NaI(Ti) detector and ED-XFR. The result shows the range of the concentration of 40 K, 226 Ra and 232 Th in soils as, 203.56 ± 0.80 to 217.39 ± 0.54 Bq/Kg, 69.39 ±0.16 to 98.07 ± 0.88 Bq/Kg and 69.52 ±0.79 to 97.88 ± 0.67 Bq/Kg respectively. The concentrations of Cr, Mn, Ni, Cu, Zn and Zr in the soil ranges from 1,083-2,380.00 mg/kg, 1,006.79-2,709.00 mg/kg, 235.70-707.40 mg/kg, 1,156.00-2,288.00 mg/kg, 0.00-560.10 mg/kg and 4,440-7,770.00 mg/kg respectively. The radionuclides highest TF of 0.99 was recorded in potato while the least with 0.44 was recorded in cabbage. Likewise, the heavy metals recorded the highest TF of 38.57 in spinach with the least as 0.086 also in spinach. The result is found to be higher than the maximum permissible limit except for 40 K which is lower. Almost all the TF are greater than 0.5 which is an indication that there is high uptake of the metals by the crops and vegetables. From the result obtained, it is evident that both the soil and the vegetables are polluted with the radionuclides and heavy metals. The soil is therefore not good for agricultural purposes unless the soil undergoes remediation.
... Copper is absorbed in the small intestine, with the duodenum serving as its primary absorption site and having an absorption efficiency of up to 60% (7). Copper in the diet is usually present in the form of Cu 2+ , but only Cu + can be absorbed and reused. ...
Copper is an essential trace element that acts as a cofactor in various enzyme active sites in the human body. It participates in numerous life activities, including lipid metabolism, energy metabolism, and neurotransmitter synthesis. The proposal of “Cuproptosis” has made copper metabolism-related pathways a research hotspot in the field of tumor therapy, which has attracted great attention. This review discusses the biological processes of copper uptake, transport, and storage in human cells. It highlights the mechanisms by which copper metabolism affects hepatocellular carcinogenesis and metastasis, including autophagy, apoptosis, vascular invasion, cuproptosis, and ferroptosis. Additionally, it summarizes the current clinical applications of copper metabolism-related drugs in antitumor therapy.
... Copper is a micronutrient that is necessary for many biological processes that are necessary for life to continue. However, excessive amounts of it can be harmful (De Roman et al., 2011). The soil's Cu concentration ranges from 576.80 mg/kg to 3,625.60 mg/kg, which is higher than Mokgolele and Likuku's (2011) findings. ...
Radionuclides and heavy metals exist in every human environment as a result of increasing anthropogenic activities. Their pollution of soil, water, and atmosphere represents a growing environmental problem affecting food quality and human health. The samples of soil used for this study were collected from Foron Bisitchi and Mazat communities of Barkin Ladi Area of Plateau state. The samples were analyzed using Canberra Model 727/727R Lead Shield Gamma ray Spectrometer with NaI(Ti) detector and ED-XFR. The result shows the range of the concentration of 40K, 226Ra and 232Th in soils as, 203.56 ± 0.80 to 217.39 ± 0.54 Bq/Kg, 69.39 ±0.16 to 98.07 ± 0.88 Bq/Kg and 69.52 ±0.79 to 97.88 ± 0.67 Bq/Kg respectively. The concentrations of Cr, Mn, Ni, Cu, Zn and Zr in the soil ranges from 1,083 – 2,380.00 mg/kg, 1,006.79 – 2,709.00 mg/kg, 235.70 – 707.40 mg/kg, 1,156.00 – 2,288.00 mg/kg, 0.00 – 560.10 mg/kg and 4,440 – 7,770.00 mg/kg respectively. The radionuclides highest TF of 0.99 was recorded in potato while the least with 0.44 was recorded in cabbage. Likewise, the heavy metals recorded the highest TF of 38.57 in spinach with the least as 0.086 also in spinach. The result is found to be higher than the maximum permissible limit except for 40K which is lower. Almost all the TF are greater than 0.5 which is an indication that there is high uptake of the metals by the crops and vegetables. From the result obtained, it is evident that both the soil and the vegetables are polluted with the radionuclides and heavy metals. The soil is therefore not good for agricultural purposes unless the soil undergoes remediation
... [35] COPPER TOXICITY Increasing evidence suggests that Cu deficiency may be more prevalent than previously thought, and Cu toxicity is uncommon under customary daily life conditions. [36] Excess of Cu absorbed in the body is generally excreted through bile. A tight control of Cu homeostasis prevents excess accumulation of Cu in the body, and therefore, acute and chronic Cu toxicities are relatively rare. ...
... Copper (Cu 2+ ) is essential for the healthy growth of biological activity because it strengthens [118] the bones and immune system, but an excessive amount of Cu 2+ can cause vomiting, pain, and disturbance of biological activity [119]. So, it is necessary to develop an easy and inexpensive sensing method to detect Cu 2+ . ...
Carbon dots (CDs) are zero-dimensional nanomaterials composed of carbon and surface groups attached to their surface. CDs have a size smaller than 10 nm and have potential applications in different fields such as metal ion detection, photodegradation of pollutants, and bio-imaging, in this review, the capabilities of CDs in metal ion detection will be described. Quantum confinement is generally viewed as the key factor contributing to the uniqueness of CDs characteristics due to their small size and the lack of attention on the surface functional groups and their roles is given, however, in this review paper, the focus will be on the functional group and the composition of CDs. The surface functional groups depend on two parameters: (i) the oxidation of precursors and (ii) their composition. The mechanism of metal ion detection is still being studied and is not fully understood. This review article emphasizes the current development and progress of CDs, focusing on metal ion detection based on a new perspective.
... Although Cu is toxic in excess, it is an essential micronutrient involved in biological processes that sustain life. Current evidence suggests that Cu deficiency may be more common than previously thought, whereas Cu toxicity is rare in everyday life situations (de Romana et al., 2011). The antioxidant function of Cu is very important; in its deficiency, Fe accumulation increases the production of hydroxyl radicals and causes oxidative damage to proteins, lipids, and DNA (Mohammadifard et al., 2019). ...
Corylus avellana L. is one of the most widely grown and traded nuts in the world. There are many types and varieties, and their ingredients are a good source of nutrients in terms of minerals. However, depending on their region and soil structure, they may contain a variety of heavy metals and toxic elements. Mineral element composition and potentially toxic element contents of different C. avellana L. varieties (15 samples) collected from the city of Giresun, which is known as the hazelnut capital of Turkey, were determined by inductively coupled plasma mass spectrometry (ICP-MS) after microwave assisted acid digestion. The elemental composition of hazelnuts is in the following ranges mg kg-1; manganese (Mn): 58.9–193, iron (Fe): 44.1–62.2, zinc (Zn): 27.0–53.8, selenium (Se): 0.01–0.12, chromium (Cr): <0.0004–0.387, copper (Cu): 16.9–25.8, magnesium (Mg): 1132–1327, calcium (Ca): 1264–1899, potassium (K): 5459-6841, sodium (Na): 1.32–7.88, lead (Pb): <0.001, cadmium (Cd): <0.001, nickel (Ni): 0.82–2.52 and arsenic (As): 0.003–0.009. These findings were used to calculate recommended dietary allowance (RDA), target hazard quotient (THQ), hazard index (HI), and carcinogenic risk (CR) values for hazelnuts. Considering the THQ values, it was determined that hazelnuts are safe for consumption by both genders. According to the carcinogenic risk calculation, all of the hazelnuts examined in this study were categorized as moderately risky in terms of Ni contents, and it was concluded that Ni may be the most important element exceeding the risk limit in hazelnuts in general.
... Skutki uboczne wynikające z nadmiernego spożycia miedzi zdarzają się rzadko, aczkolwiek mogą wystąpić w postaci takich objawów, jak: nudności, wymioty, niedociśnienie, żółtaczka, biegunka [41]. Nieustanne przyjmowanie dużej ilości miedzi może prowadzić natomiast do uszkodzenia wątroby i nerek [26]. W przypadku choroby Wilsona dochodzi do patologicznego gromadzenia się miedzi, co upośledza funkcje wątroby. ...
Miedź od wieków była używana do eradykacji zakażeń bakteryjnych. Pierwiastek ten ma nie tylko działanie bakteriobójcze, ale również przyśpiesza proces angiogenezy i epitelizacji. W niniejszej pracy omówiono rolę miedzi w procesie gojenia ran.
For centuries copper has been used to fight bacterial infections. This element not only has a bactericidal effect, but it also accelerates the process of angiogenesis and epithelization. In the presented paper, the role of copper in the wound healing process has been discussed.
... These nanoparticles are also used in biomedical applications [12,13]. It has been sighted that the intake of copper is less than the recommended level (2 mg/day) in a substantial fraction of the population [14]. Since copper is used in various biological processes, its insufficiency can lead to risks or manifestations of ischemic heart disease (IHD) [15]. ...
Nanoparticles (NPs) have gained recognition for diagnosis, drug delivery, and therapy in fatal diseases. This review focuses on the benefits of green synthesis of bioinspired NPs using various plant extract (containing various biomolecules such as sugars, proteins, and other phytochemical compounds) and their therapeutic application in cardiovascular diseases (CVDs). Multiple factors including inflammation, mitochondrial and cardiomyocyte mutations, endothelial cell apoptosis, and administration of non-cardiac drugs, can trigger the cause of cardiac disorders. Furthermore, the interruption of reactive oxygen species (ROS) synchronization from mitochondria causes oxidative stress in the cardiac system, leading to chronic diseases such as atherosclerosis and myocardial infarction. NPs can decrease the interaction with biomolecules and prevent the incitement of ROS. Understanding this mechanism can pave the way for using green synthesized elemental NPs to reduce the risk of CVD. This review delivers information on the different methods, classifications, mechanisms and benefits of using NPs, as well as the formation and progression of CVDs and their effects on the body.
... There are no studies available regarding measures of plasma levels of copper. It is important to note that reduced levels of copper in serum are not typically reported because the normal body mechanisms of copper regulation are extremely sensitive and can protect against deficiencies and excesses [29]. ...
Objective:
To analyze the nutritional status and plasma levels of vitamins and minerals in a cohort of Chilean children between 4 and 14 years old from three cities in Chile (Santiago, Antofagasta, and Concepcion).
Design:
This is a descriptive analysis of micronutrient levels in Chilean children as it relates to obesity and food consumption.
Setting:
This study included 1235 children from schools in Santiago (central area), Antofagasta (northern area), and Concepcion (southern area) in Chile.
Results:
Plasma levels of micronutrients revealed deficiencies in children from all these cities. Copper (26.4%) and calcium (33.0%) deficiencies were found in the children from Antofagasta, whereas iron (26.7%) and zinc (20.8%) deficiencies were found in the children from Concepcion and Santiago, respectively. The percentage of children with vitamin D deficiencies was exceptionally high in all cities (over 78%). The analysis of micronutrients and nutritional status revealed that vitamin D deficiencies were significantly higher (p = 0.02) in overweight children, particularly in Antofagasta. In the analysis of the nutritional status of children and their food consumption habits, the proportion of overweight and obesity was significantly higher (p = 0.001) in children that skipped breakfast compared to children that did not. Finally, children from low socioeconomic levels were significantly more overweight and obese compared to children from high socioeconomic levels (p < 0.05).
Conclusions:
this is the first study to describe plasma levels of micronutrients in Chilean children and adolescents. High percentages of obesity, overweight, and vitamin D deficiency were detected in children. These results are of significant relevance to future public health policies in Chile.
... Copper is a vital mineral that aids in the production of neurotransmitters, connective tissue, neuropeptides, and energy [25]. Amounts of the mineral in food vary based on the season, soil quality, and water sources [26]. A case study found copper deficiency-induced anemia and neutropenia in a child who changed from a liquid to solid ketogenic diet [27]. ...
Objective:
The aim of this study was to evaluate the macronutrient and micronutrient intake and status in youth with type 1 diabetes mellitus (T1DM) following the consumption of a low-carbohydrate diet (LCD).
Research methods and procedures:
In a prospective intervention clinical trial, adolescents with T1DM using a continuous glucose monitoring device were enrolled. Following a cooking workshop, each participant received a personalized diet regime based on LCD (50-80 g carbohydrate/day). A Food Frequency Questionnaire was administered, and laboratory tests were taken before and 6 months following the intervention. Twenty participants were enrolled.
Results:
The median age was 17 years (15; 19), and the median diabetes duration was 10 years (8; 12). During the six-months intervention, carbohydrate intake decreased from 266 g (204; 316) to 87 g (68; 95) (p = 0.004). Energy intake, the energy percent from ultra-processed food, and fiber intake decreased (p = 0.001, p = 0.024, and p < 0.0001, respectively). These changes were accompanied by declines in BMI z-score (p = 0.019) and waist-circumference percentile (p = 0.007). Improvement was observed in the median HbA1c from 8.1% (7.5; 9.4) to 7.7% (6.9; 8.2) (p = 0.021). Significant declines below the DRI were shown in median intake levels of iron, calcium, vitamin B1, and folate.
Conclusions:
The LCD lowered ultra-processed food consumption, BMI z-scores and the indices of central obesity. However, LCDs require close nutritional monitoring due to the possibility of nutrient deficiencies.
... However, Cu was reported as highly toxic in aquatic mediums and to have adverse effects on fish, invertebrates, and amphibians, with all three categories being vulnerable to chronic exposure ( Kundu et al., 2017 ). Also, prolonged exposure to high levels of Cu can be toxic for humans and may prompt symptoms like damage to the liver and kidney, localized death of living cells, and hypotension ( de Romaña, Olivares, Uauy & Araya, 2011 ;Ezeonyejiaku, Obiakor & Ezenwelu, 2011 ). The copper concentration determined in the tilapia fish feeds of the current study was far below the recommended FAO guideline of 10 mg/kg ( FAO/WHO, 2001 ;Kundu et al., 2017 ;FAO, 1983 ). ...
Tilapia, the third most cultured fish, is a part of the daily diet of more than 50% of the population of Bangladesh. Thus, adequate nutrition and toxic metal-free tilapia fish feeds are the prerequisites of sustainable aquaculture. The present study was carried out to investigate the nutritional profile and heavy metal pollution in nursery, grower, and finisher types of feeds of tilapia commercially available in Bangladesh. The proximate composition (moisture, protein, lipid, ash, crude fibre, and carbohydrate), mineral nutrients, fatty acid profile, and heavy metals (Pb, Cd, Cr, Ni, Cu, and Zn) of feed samples were assessed. Low protein content and the absence of essential fatty acids mark the feeds as low-quality diets. A significant amount of trace metals were also detected in the feeds, posing a direct threat to the health of the fish and, ultimately, to consumers. The results revealed the highest Zn concentration in all tilapia feed samples. The descending order of heavy metal concentrations was identified as Zn>Ni>Pb>Cu>Cr in nursery feeds, Zn>Cu>Cr in grower feeds, and Zn>Ni>Cu>Cr>Cd in finisher feeds. Pb and Cr values were higher than the recommended values set by FAO. Therefore, strong monitoring is recommended to ensure the optimum quality and safety feeds.
... 5 The amount and availability of copper in cells needs to be tightly regulated, since too little copper will lead to cellular starvation while too much copper will lead to cellular poisioning. 6 This concept can be utilised in controlling growth and proliferation of cells to combat diseases. For example, increasing copper levels in the cellular environment by dosing with copper-releasing complexes can lead to destruction of cancer cells and disruption of bacterial cell growth. ...
Copper Pyrithione, [Cu(PyS) 2 ] has shown excellent biological activity against cancer cells and bacterial cells, however, it has extremely low aqueous solubility, limiting its applicability. Herein, we report a series of...
... This neurodegenerative disorder results in impaired Cu absorption, causing widespread effects, including bone lesions such as delayed growth, generalized osteoporosis, and exacerbated appendages of long bones [140]. The level of bone changes in Cu deficiency is mainly determined by functional defects in osteoblasts, while osteoclast activity remains unchanged [141,142]. Unaltered osteoclast activity in Cu deficiency, accompanied by low osteoblast activity, contributes to impaired bone tissue transformation leading to osteopenia [127]. The effects of Cu deficiency are mediated by various enzymes in which Cu is a cofactor, including amine oxidase, ceruloplasmin, cytochrome oxidase, dopamine monooxygenase, extracellular superoxide dismutase, lysyl oxidase, Cu/Zn superoxide dismutase, and tyrosinase. ...
The paper presents the current understanding on the effects of five metals on bone tissue, namely iron, zinc, copper, cadmium, and mercury. Iron, zinc, and copper contribute significantly to human and animal metabolism when present in sufficient amounts, but their excess or shortage increases the risk of developing bone disorders. In contrast, cadmium and mercury serve no physiological purpose and their long-term accumulation damages the osteoarticular system. We discuss the methods of action and interactions between the discussed elements as well as the concentrations of each element in distinct bone structures.
... mg/day as per WHO. When the concentration of Cu 2+ crosses the limit, it causes diseases like prion disease, Alzheimer's disease, and Wilson's disease [109][110][111][112][113]. ...
Metal cations such as Zn²⁺, Al³⁺, Hg²⁺, Cd²⁺, Sn²⁺, Fe²⁺, Fe³⁺ and Cu²⁺ play important roles in biology, medicine, and the environment. However, when these are not maintained in proper concentration, they can be lethal to life. Therefore, selective sensing of metal cations is of great importance in understanding various metabolic processes, disease diagnosis, checking the purity of environmental samples, and detecting toxic analytes. Schiff base probes have been largely used in designing fluorescent sensors for sensing metal ions because of their easy processing, availability, fast response time, and low detection limit. Herein, an in-depth report on metal ions recognition by some Schiff base fluorescent sensors, their sensing mechanism, their practical applicability in cell imaging, building logic gates, and analysis of real-life samples has been presented. The metal ions having biological, industrial, and environmental significance are targeted. The compiled information is expected to prove beneficial in designing and synthesis of the related Schiff base fluorescent sensors.
... As an essential micronutrient, it is involved in a variety of biological processes. However, it is toxic when present in excess with the most noticeable chronic effect being liver damage (De Romaña et al. 2011). Usual copper contents in wild species are from 10 to 75 mg kg À1 (Kala c 2019). ...
Five wild edible mushroom species, namely, Macrolepiota mastoidea, Macrolepiota konradii, Macrolepiota procera, Suillus collinitus and Cuphophyllus pratensis, were studied for their trace element contents by inductively coupled plasma – mass spectrometry (ICP-MS). The potential health risk assessments of children and adults were evaluated by the weekly intake (EWI), target hazard quotients (THQ), hazard index (HI) and cancer risk (CR). None of the analyzed elements exceeded the THQ value more than 1, but the HI values indicated that M. mastoidea and S. collinitus may be dangerous to children’s health. The values of CR for As and Cd for children in all mushroom species were above 1 × 10⁻⁴ suggesting that there was a potential health risk. The CR values for adults suggest that all mushrooms may pose a threat to human health related to Cd.
... Nevertheless, two other platyrrhine primate species, spider monkeys (Laska et al., 2000) and squirrel monkeys (Laska, 2001), also displayed significant positive correlations between their food preferences and copper content of the food items tested, whereas three catarrhine primate species, pigtail macaques (Laska, 2001), white-handed gibbons (Jildmalm et al., 2008) and ringtailed lemurs (Hansell et al., 2020) did not. Considering that copper deficiency in nonhuman primates has been associated with osteoporosis, cardiovascular disease, and poor immune response (Lopez de Romana et al., 2011) future studies on the diet of platyrrhine primates under human care should therefore consider a sufficient supply of this trace mineral. ...
The role that single nutrients may play for food choices in nonhuman primates is not fully understood. White-faced sakis ( Pithecia pithecia ) are unusual among frugivorous primates as they do not serve as seed dispersers but rather exploit the seeds they consume, presumably for their high contents of lipids and proteins. Therefore, we assessed the occurrence of spontaneous food preferences in zoo-housed white-faced sakis and analyzed whether these preferences correlate with nutrient composition. Using a two-alternative choice test, we repeatedly presented three female and two male sakis with all possible binary combinations of 15 types of food that are part of their diet under human care, and found them to display the following rank order of preference: peanut > hazelnut > avocado > melon > egg > apple > mealworms > beetroot > carrot > cucumber > cabbage > tomato > sweet potato > broccoli > eggplant. This preference ranking significantly and positively correlated with the total energy content of the food items. However, we found the strongest positive correlation among the three macronutrients providing metabolic energy between the sakis’ food preferences and lipid content. This is remarkable as all other primate species tested so far using this method displayed the strongest correlation with carbohydrates instead. Together with our finding that the sakis significantly preferred foods high in mono-unsaturated fatty acids, the building blocks of lipids, these results support the notion that white-faced sakis exploit the lipids contained in seeds to meet their requirements of metabolic energy.
... 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. ...
Background: The relationship between strong immune response to infections and trace elements such as selenium (Se) and copper (Cu) is well documented.
... Its concentration is highest in the liver, brain, kidneys and heart. [13,14] Copper is an important component of many oxidoreductase enzymes that play an important role in the generation of energy in the cell. The activity of these enzymes is highest in the heart, brain, liver and kidneys. ...
Introduction: Smoking can cause accumulation of some harmful chemical elements in tissues such as heavy metals cadmium (Cd), lead (Pb), mercury (Hg), arsenic (As), cesium (Cs), etc. Smoking can also cause disturbances in the metabolism of trace elements such as copper, zinc and selenium. This is manifested by a change in their levels in biological material, primarily in blood, urine, hair and nails. The aim of the study was to determine the differences in the concentrations of mercury in urine and copper in blood serum of smokers and ex- smokers in relation to non-smokers. Methods: The study included 108 respondents divided into three groups. The first group of respondents consists of regular smokers (n=51), the second group of ex-smokers (n=38) and the third group of respondents who have never consumed tobacco (n=17). Determination of the level of mercury in urine was performed by the method of atomic absorption spectrophotometry with an electrothermal atomizer. Level of copper in blood serum was performed by spectrophotometric method without deproteinization. Results: The analysis showed that there is no statistically significant difference in the level of mercury in the urine of smokers compared to non-smokers and ex-smokers (p=0.09). There is a statistically significant difference in copper values in the blood serum compared to the examined groups (p=0.039). Conclusion: Smoking did not prove to be a significant factor for increased concentration of mercury in the urine, but it significantly affected the level of copper in the blood serum.
... Because of the strong mutual interaction between metabolic abnormalities and obesity, abdominal obesity is even regarded as a main component for defining MetS (Grundy et al. 2005). Considering serum copper concentration could affect the status of fat metabolism, inflammation, oxidative stress, nonalcoholic fatty liver (NAFLD), MetS, and insulin resistance (Chen et al. 2021;de Romana et al. 2011;Krishnamoorthy et al. 2016;Lu et al. Lu et al. 2021), and these abovementioned factors were highly associated with the occurrence of obesity Responsible Editor: Lotfi Aleya Hongrong Wu and Qingqi Li contributed equally to this work. ...
Excessive serum copper has multiple effects on human health, while the association between copper and obesity remains unclear. The objective of this study is to examine the associations of serum copper concentrations with obesity and adiposity measures, including body fat composition and distribution among adults in the USA. This analysis utilized data from the National Health and Nutrition Examination Survey (NHANES) (2011–2016). A total of 7285 adults aged 18 years or older who had serum copper measures were included in this cross-sectional study. Multi-linear regression and logistic regression were used to estimate the independent risky effect of copper on fat deposition and all-cause mortality. Moreover, these associations were analyzed in stratification analysis by gender, age, and physical activity (PA). Generally, we found that participants who were females, non-Hispanic Black, or with inactive PA tended to have a higher serum level of copper. In addition, we observed positive associations between serum copper and adiposity measurements. Furthermore, a serum copper level higher than 133.9 μg/dL was a risk factor for all-cause mortality, which doubled the odds ratio of all-cause mortality compared to the normal serum copper level. Serum copper was positively associated with fat deposition of whole body and regional parts, and all-cause mortality. Furthermore, the effects of copper on fat distribution were also significant and could be modified by age, gender, and PA.
... Trace amounts of Cu are essential for the functioning of various biological processes in humans, plants, and animals. Nevertheless, higher Cu doses are toxic [86]. Therefore, the leaching of Cu into the environment must be controlled. ...
Most halogenated organic compounds (HOCs) are toxic and carcinogenic, hence unwanted in the environment. Several technologies exist for the treatment of both legacy and newly contaminated zones. In many contaminated subsurface environments , nano zero-valent iron (nZVI) as a reagent is the tool of choice, while palladium (Pd) as a catalyst faces technical challenges. A system comprising metallic copper and borohydride as a reducing agent (referred herein as copper-borohydride system, CBHS) provides an alternative to nZVI and Pd. This chapter presents a deeper understanding of the CBHS for the treatment of HOCs by highlighting the state of knowledge related to the i) type and classes of compounds that are treatable, ii) possible reaction pathways for their transformation, iii) specific metal activities for transformation of selected classes of HOCs, iv) influence of common water constituents on catalyst stability, and v) future perspectives regarding its application in water treatment applications. Furthermore, an up-to-date discussion is presented regarding the available techniques for the synthesis of copper nanoparticles. Based on the evaluation criteria including product selectivity patterns, amount and the fate of intermediates, and metal cost and stabilities in water, the most suitable application areas for Cu, Pd, and nZVI are presented as recommendations.
... Cu 2+ is one of the most abundant substances found in the environment amongst the heavy metals which was also defined as a nutrient for many life forms [3]. It is an essential component of cytochrome c oxidase, which binds oxygen in the respiratory system, and also acts as a cofactor for various enzymes related to hemoglobin formation and function, carbohydrate metabolism, catecholamine biosynthesis, etc. [4].The presence of this ion in trace amounts in the body is of vital importance for humans and animals [5]. ...
A facile and label-free detection method based on the formation of the G-quadruplex structure of Thioflavin T and a DNA sequence was developed for rapid and sensitive detection of copper (Cu 2+) ion. The DNA sequence with many guanine (G) repeats has the potential to form a G-quadruplex structure and exhibits high selectivity to Cu 2+. ThT promotes the formation of the G-quadruplex structure resulting in high fluorescence intensity because of its fluorescence molecular rotor characteristic. As opposed to, when the DNA sequence binds to its target in the presence of Cu 2+ , conformational changes occur, resulting in ThT dissociation and a substantial decrease in fluorescence intensity. By virtue of this change, unlabeled, low-cost, sensitive, and selective detection of Cu 2+ was achieved and not interfered by many other ions. The proposed method has high sensitivity and selectivity, with a detection limit of 30.7 nM, allowing it to directly measure Cu 2+ in contaminated water samples in a wide linear range from 0.1 to 100 µM with a high recovery rate.
... Copper is one of the important elements that contributes to red blood cell production, hormone formation and acts against oxida-tive damage (López-Alonso and Miranda, 2020), and it can be toxic when it is in high concentration due to the fact that ruminants do not have efficient Cu regulatory mechanisms (NRC, 2005;de Romaña et al., 2011;Mercer, 2001). Zinc is needed in protein synthesis and other biochemical reactions (Miller, 1970), and its deficiency can lead to the reduction of growth and appetites (Chesters, 1983). ...
The objective of this study was to investigate the effect of the harvesting site on the mineral concentration of selected browse species found in semi-arid areas of South Africa (North West and Limpopo Province sites). Five trees from each of the 52 woody browse species were randomly identified and harvested in the North West and Limpopo provinces, South Africa, dried and ground for laboratory analysis. One-way ANOVA was used to analyse the mineral composition of browse species that were not common in both harvesting sites, while a two-way factorial design within a completely randomized experimental design was used to analyse the mineral composition of browse species that were common in both harvesting sites. MANOVA tests were also used in order to assess the species and harvesting site effects on mineral concentrations of species common in both sites. Through ANOVA and MANOVA, there were significant species, harvesting site, and species × harvesting stage effects on all the measured parameters (both macro and micro mineral elements). Phosphorus and calcium concentrations were the highest in Adansonia digitata species, whereas the lowest was obtained in Androstachys jonhsonii browse species in the Limpopo harvesting site. Within each province, Schinus molle found in the North-West site had the highest phosphorus, potassium and sodium values when compared to all species within the same province. Vachellia nilotica subsp. kraussiana, M. azedarach and Ziziphus mucronata found in Limpopo province had the highest level of magnesium when compared to other species found within the same province. Senegalia caffra, Grewia flava, Vachellia karroo, Vachellia nilotica subsp. kraussiana, Searsia leptodictya and Melia azedarach found in the Limpopo province had the highest phosphorus level when compared to the same species found in the North West province. Senegalia caffra, Peltophorum africanum, Grewia flava, Vachellia hebeclada and Terminalia sericea found in the North West province had the highest iron levels when compared to the same species found in Limpopo province. There is a need to provide supplementation to those animals exposed to species that have a lower concentration of certain elements.
... The small amount of Cu found in nettle leaves does not contradict with the requirement of the metal for proper functioning of the body, because this metal is required in small amount (Cu = 0.3 mg/day) as a constituent of vitamin B12 and Cu = 3.5 mg/day [24]. As can be seen from Figure 7 zinc is the most concentrated (17.3mg/100g) in Woynadega and Iron is the most concentrated heavy metals in all nettles with values 14.686mg/100g while Cd the lowest. ...
Mopane caterpillars ( Gonimbrasia belina ) are one of the most consumed edible insects in Southern Africa, and they contribute nutritional benefits to human health. However, their contribution to the food and nutritional security can be hindered by food safety concerns due to heavy metal contamination associated with harvesting, processing and poor post-harvest practices. This study investigated the effectiveness of post-harvest practices (degutting, charcoal roasting and sun drying, boiling, frying and open pan roasting) in reducing the heavy metal contaminants (cadmium (Cd), mercury (Hg), lead (Pb), nickel (Ni), aluminium (Al), zinc (Zn), copper (Cu) and iron (Fe)) in mopane caterpillar sourced from Gwanda district in Zimbabwe. The post-harvest practice categories used in this study included: unprocessed (ungutted and naturally degutted samples), processed (manually degutted, and charcoal roasted and sun-dried), and cooked (boiled and salted; boiled, salted and roasted, and boiled, salted and fried) samples. An atomic absorption spectrometry (AAS) was used for quantification of metals and the values detected were used to assess health risks to consumers using a quantitative risk assessment calculation method. The unprocessed and manually degutted samples showed higher levels Cd and traces of Pb, while charcoal roasting and sun drying resulted in elevated levels of Al, Zn, Cu and Fe. Hg and Ni were not detected in any of the unprocessed, processed or cooked samples. Cooking processes resulted in reduction of the concentrations of detected metals to levels within the permissible values. The health risk assessment disclosed noncarcinogenic risks based on the high hazard index (HI) values (HI > 1) in unprocessed, processed, boiled and salted, and boiled, salted and roasted samples, indicating that caution should be taken. The overall findings from the study shows that by cooking mopane caterpillars through boiling and frying, health risks associated with heavy metal contamination can be reduced.
Background
Prenatal exposure to trace metals can have adverse effects on health and increase the risk of developing certain diseases. This study aimed to determine the effectiveness of giving women advice to reduce their exposure to trace metals during pregnancy or prior to conception. The study also examined differences in exposure between rural and urban environments in southern France.
Methods
In this prospective study, pregnant women or those intending to conceive were recruited from two medical centers for gynecology/obstetrics (rural location: Saint-Rémy-de-Provence; urban location: Marseille). Hair samples were collected and analyzed to determine the levels of exposure to trace metals. Participants with ‘risky’ levels were given corresponding advice sheets on how to reduce their exposure or, for certain metals, they were encouraged to find out about potential sources of exposure. A second hair sample was collected and analyzed 3 months later.
Results
It was found that 109 women had ‘risky’ levels of exposure to trace metals, out of a total of 184 women (59.2 %). Cerium was the most frequently identified metal (N = 26), followed by nickel (N = 23), and titanium (N = 19). There were more women at the urban center with ‘risky’ levels (56/86; 65.1 %) than at the rural center (53/98; 54.1 %), but this difference was not statistically significant (p = 0.13). Advice sheets were given to 64 of the 109 participants with ‘risky’ levels (58.7 %), but only 21 returned for the second hair analysis. Of these, 14 were found to have reduced their exposure, which corresponds to just 12.8 % (14/109) of the participants with ‘risky’ levels.
Conclusions
These results indicate that it would be helpful to develop new interventions to reduce trace metal exposure during or prior to pregnancy.
Background
Copper (Cu) is one of the minerals that has a key role in human health and cell metabolism. Recent reports show Cu homeostasis and Cu-induced cell death play crucial role in the pathogenesis of cardiovascular disease (CVD). However, the epidemiology evidence association between serum Cu and risk of cardiovascular disease is limited.
Objective
This national cross-sectional study aimed to assess the association between serum Cu and the risk of CVD.
Methods
Dataset were from the Nation Health and Nutrition Examination Survey (NHANES) 2011–2016. Weighted logistic regression model and dose-response curve were applied.
Results
A total of 5,154 participants were included, representing 21,995,1371 Americans adult. The average level of serum Cu was 18.6 µmol/L, and the overall prevalence of CVD was 7.4%. Serum Cu values in female, middle-aged, and non-Hispanic Black subjects were higher (P < .05). Subjects with a high prevalence of CVD had higher serum Cu levels than non-CVD subjects (P < .05). Those in tertile 3 had a significantly higher prevalence of CVD (OR: 1.64; 95% CI 1.16–2.33) than those in the lowest tertile. Continuous variable analysis showed that serum Cu was positively associated with the prevalence of CVD (per 1 SD; OR: 1.23; 95% CI: 1.03–1.47). The dose-response curve demonstrated a linear association of Cu levels with CVD prevalence (P-nonlinear = 0.40), with the OR of CVD doubled at serum Cu levels of 20.0 µmol/L.
Conclusion
Excess serum Cu is associated with the prevalence of CVD among adult Americans.
The bioaccumulation of heavy metals (HMs) in marine fish is a growing global concern due to potential human health risks. The study analyzed HM in the muscle tissue, gills, and gut of adult male and female cape horse mackerel and slinger seabream caught in the polluted Durban Basin and pristine Cape Vidal from April 2018 to February 2019. Results revealed interspecific, spatial, and organ-specific variability in HM levels. In the Durban Basin, slinger seabream had bioaccumulation (in mg/kg) of As (2.3 ± 0.2), Cr (2.6 ± 0.2), Ni (2.0 ± 0.1), and Pb (4.1 ± 0.3) while cape horse mackerel had Ni (1.6 ± 0.2), Pb (4.7 ± 0.6), and Zn (52 ± 3.01) exceeding World Health Organization (WHO) regulatory limits. Metal pollution index (MPI) values were also higher in Durban Basin (> 5.13) than Cape Vidal (< 3.32) for both species' muscles. Liver and gills of slinger seabream and gut of cape horse mackerel exhibited higher HM accumulation patterns proportionate to the environmental concentrations, indicating the bioindicative potential of HM pollution by the two species. Risk assessment indicated that both fish species had target hazard quotient > 1 for Cr, and target cancer risk < 10-4 for Pb, implying significant potential non-carcinogenic and carcinogenic health risks associated with fish consumption from the Durban Basin. The study recommends daily consumption limits of 16 g/day for slinger seabream and 14 g/day for cape horse mackerel to ensure health safety. The findings contribute to the understanding of HM pollution in the Durban Basin and provide important information for decision-makers and policymakers in developing effective strategies to mitigate and manage HM contamination in fish populations.
The use of traditional medicine is increasing dramatically worldwide. In Ethiopia, people largely depend on the use of traditional medicinal plants as herbal remedies. However, the effectiveness of medicinal plants is affected by the presence of heavy metals. Thus, this study aimed to evaluate the distribution of heavy metals in selected medicinal plant roots and the soils in which they were grown. A total of five root and soil samples in triplicate were used for analysis. A wet digestion procedure involving the use of a mixture of strong acids was used for the analysis of plant and soil samples. Based on the results, the concentrations of Zn (21.82mg/kg) and Fe (7.78mg/kg) were higher in Solanum incanum and Carissa spinarum plant samples, respectively, than in the other plants. The concentrations of Mn, Cu, and Pb ranged from 1.70 ˗ 4.22mg/kg, 1.34 ˗ 3.43mg/kg, and 0.14 ˗ 0.34 mg/kg, respectively, but Cd was detected only in Carissa spinarum (0.15 mg/kg) and in Solanum incunm (0.21mg/kg). Regarding the contents of the metals in the soil samples, Zn (15.45 ˗ 44.3 mg/kg) is the most dominant metal, followed by Mn (9.54-23.07mg/kg), Fe (7.58 ˗ 12.68 mg/kg), Cu (3.16-12.55 mg/kg), and Pb (0.14-2.85 mg/kg) whereas Cd was detected only in Boyegararsa soil (0.21 mg/kg) and Warabaye (0.65 mg/kg) soil samples. The results indicated that the contents of the metals studied did not exceed the permissible limit for medicinal plants set by WHO/FAO. Further studies should be carried out on the bioavailability of toxic heavy metals in traditional herbal medicines.
Aim: To assess the association serum levels of selenium (Se) and copper (Cu) with symptoms and IgG immune response to SARS-CoV-2. Patients & methods/materials: Blood samples and nasopharyngeal swabs were obtained from 126 COVID-19 patients with mild and severe symptoms. The serum levels of Cu and Se were measured by atomic-absorption spectrophotometry. Results & conclusion: Mean Se was higher in patients with mild symptoms and IgG nonresponders, whereas mean Cu was higher in patients with severe symptoms and IgG responders. The Cu/Se ratio was lower in patients with no IgG responses to infection and mild symptoms versus IgG responders with severe symptoms. These results suggest the Cu/Se ratio as a nutritional biomarker of severity and IgG immune response in COVID-19 patients.
Настоящата книга представя актуални данни за обмяната на
микроелемента мед в контекста на взаимовръзката между различните микроелементи в организма, които споделят общи пътища на
обмяна. Значително внимание е отделено на лабораторните аспекти в микроелементния анализ, с детайлно характеризиране на отделните етапи в общия процес на изследване – преданалитичен,
аналитичен и следаналитичен. Тяхното познаване е гаранция за висока надеждност на резултатите.
Есенциалният характер на микроелементите върви ръка за ръка
с тяхната дуалистична природа. Разбирането за понижение или повишение на тяхната бионаличност следва да се тълкува в по-общия
план на разпределението им, от една страна, на клетъчно ниво, а
от друга – на системно. Множество механизми за поддържане на
хомеостазата на микроелементите в организма се преплитат и взаимно се контролират, като процесите са насочени към строг контрол
върху свободните фракции на йоните на металите, защото те са с
висока окислително-редукционна активност. Токсичните увреди при
дисбаланс преминават през механизма на оксидативния стрес.
Източник на хранителни вещества за организма са храната, водата и различни медикаменти. Върху организма влияние оказват и
фактори от околната среда. Това поставя въпроса за познаването на
взаимовръзката между генетичната предразположеност и действието на епигенетични фактори, някои от които могат да послужат като
средства за профилактика и лечение.
Мултиелементният анализ може да намери място в рутинната
клиничнолабораторната практика. Резултатите от тези анализи ще
са полезни както при редките заболявания, така и при редица социалнозначими състояния.
The bioaccumulation of heavy metals (HMs) in marine fish is a growing global concern due to potential health risks. The study analysed HM in the muscle tissue, gills, and gut of cape horse mackerel and slinger seabream caught in the polluted Durban Basin and pristine Cape Vidal from April 2018 to February 2019. Results revealed interspecific, spatial, and organ-specific variability in HM levels. In the Durban basin, slinger seabream had bioaccumulation (in mg/kg) of As (2.3± 0.2 ) , Cr (2.6±0.2), Ni (2.0±0.1), and Pb (4.1±0.3) while cape horse mackerel had Ni (1.6±0.2), Pb (4.7±0.6), and Zn (52±3.01) exceeding WHO regulatory limits. Metal pollution index (MPI) values were also higher in Durban Basin (>5.13) than Cape Vidal (<3.32) for both species muscles. Liver and gills of slinger seabream and gut of cape horse mackerel exhibited higher HM accumulation patterns proportionate to the environmental concentrations, indicating the bioindicative potential of HM pollution by the two species. Risk assessment indicated that both fish species had target hazard quotient (THQ) > 1 for Cr, and target cancer risk (TR) < 10 ⁻⁴ for Pb, implying significant non-carcinogenic and carcinogenic health risks associated with fish consumption from the Durban Basin. The study recommends daily consumption limits of 16 g/day for slinger seabream and 14 g/day for cape horse mackerel to ensure health safety. The findings contribute to the understanding of HM pollution in the Durban basin and provide important information for decision-makers and policymakers in developing effective strategies to mitigate and manage HM contamination in fish populations.
Cirrhosis is a serious liver disease with an unclear etiology and pathogenesis. Previous studies suggest a correlation between circulating copper and cirrhosis. However, whether circulating copper is a risk factor for cirrhosis is currently controversial because the liver is a major organ of copper metabolism and cirrhosis affects copper circulation. To address this, we used a mendelian randomization to explore the effect of circulating copper concentration on the risk of cirrhosis. We selected instrumental variables (IVs) of circulating copper from genome-wide association studies and analyzed two datasets from FinnGen, one for cirrhosis in general and the other for cirrhosis caused by non-alcoholic fatty liver disease (NAFLD). The inverse-variance weighted method was primarily used for mendelian randomization analysis. We created two SNP IVs that were associated with circulating copper, and their genetic associations with cirrhosis were extracted from the two datasets. The cirrhosis-related dataset included 811 cirrhosis patients and 273,592 controls, while the dataset for cirrhosis caused by NAFLD included 437 cirrhosis patients and 216,861 controls. Mendelian randomization analysis predicted a significant association between higher levels of circulating copper and increased risk of cirrhosis of liver (OR = 1.82, 95% CI: 1.30 to 2.54, P < 0.001). Additionally, higher levels of circulating copper were also associated with increased risk of cirrhosis of liver caused by NAFLD (OR = 1.68, 95% CI: 1.08 to 2.60, P = 0.021). The study suggests that higher levels of circulating copper may be a pathogenic risk factor for cirrhosis, providing important insights for the prevention and treatment of cirrhosis.
Simple Summary
Copper (Cu) is a redox active metal and an essential trace element for human health, which is required as a cofactor for enzymes involved in numerous important cellular functions and pathways. Chronic stress is a common environmental issue, which induces nutritional or metabolic disorders and leads to a significant adverse health consequence. In this study, corticosterone drinking water was used to simulate chronic stress to explore the effects of stress on the disorder of copper metabolism and its regulatory mechanism in mice. It was proved that corticosterone impairs copper transport by down-regulating intestinal CTR1 expression via GR-mediated transcriptional inhibition in vivo and in vitro. This study provides the theoretical basis for regulating the copper homeostasis under chronic stress.
Abstract
Numerous studies have discovered that chronic stress induces metabolic disorders by affecting iron and zinc metabolism, but the relationship between chronic stress and copper metabolism remains unclear. Here, we explore the influence of chronic corticosterone (CORT) exposure on copper metabolism and its regulatory mechanism in mice. Mice were treated with 100 μg/mL CORT in drinking water for a 4-week trial. We found that CORT treatment resulted in a significant decrease in plasma copper level, plasma ceruloplasmin activity, plasma and liver Cu/Zn-SOD activity, hepatic copper content, and liver metallothionein content in mice. CORT treatment led to the reduction in duodenal expression of copper transporter 1 (CTR1), duodenal cytochrome b (DCYTB), and ATPase copper-transporting alpha (ATP7A) at the mRNA and protein level in mice. CORT treatment activated nuclear glucocorticoid receptor (GR) and down-regulated CRT1 expression in Caco-2 cells, whereas these phenotypes were reversible by an antagonist of GR, RU486. Chromatin immunoprecipitation analysis revealed that GR bound to the Ctr1 promoter in Caco-2 cells. Transient transfection assays in Caco-2 cells demonstrated that the Ctr1 promoter was responsive to the CORT-activated glucocorticoid receptor, whereas mutation/deletion of the glucocorticoid receptor element (GRE) markedly impaired activation of the Ctr1 promoter. In addition, CORT-induced downregulation of Ctr1 promoter activity was markedly attenuated in Caco-2 cells when RU486 was added. These findings present a novel molecular target for CORT that down-regulates intestinal CTR1 expression via GR-mediated trans-repression in mice.
Regardless of the essential role of copper (Cu) in the physiological regulation process of mammalian reproduction, excessive exposure to Cu triggers the meiotic defects of porcine oocytes via compromising the mitochondrial functions. However, the connections between the excessive Cu exposure and meiotic defects of ovine oocytes have not been reported. In this study, the effect of copper sulfate (CuSO4) exposure on the meiotic potentials of ovine oocytes was analyzed. Subsequently, the ameliorative effect of glutathione (GSH) supplementation on the meiotic defects of CuSO4 exposed ovine oocytes was investigated. For these purposes, the in vitro maturation (IVM) of ovine cumulus oocyte complexes (COCs) was conducted in the presence of 5, 10, 20 and 40 μg/mL of CuSO4 supplementation. Subsequently, different concentrations of GSH (2, 4 and 8 mM) were added to the IVM medium containing CuSO4 solution. After IVM, the assay, including nuclear maturation, spindle organization, chromosome alignment, cytoskeleton assembly, cortical granule (CGs) dynamics, mitochondrial function, reactive oxygen species (ROS) generation, apoptosis, epigenetic modification and fertilization capacity of ovine oocytes were performed. The results showed that excessive Cu exposure triggered the meiotic defects of ovine oocytes via promoting the mitochondrial dysfunction related oxidative stress damage. Moreover, the GSH supplementation, not only ameliorated the decreased maturation potential and fertilization defect of CuSO4 exposed oocytes, but inhibited the mitochondrial dysfunction related oxidative stress damage, ROS generation, apoptosis and altered H3K27me3 expression in the CuSO4 exposed oocytes. Combined with the gene expression pattern, the finding in the present study provided fundamental bases for the ameliorative effect of GSH supplementation on the meiotic defects of CuSO4 exposed oocytes via inhibiting the mitochondrial dysfunctions, further benefiting these potential applications of GSH supplementation in the mammalian IVM system and livestock breeding suffering from the excessive Cu exposure.
Copper (Cu) is an essential trace element with tightly regulated homeostasis in the body. Alterations in homeostasis may have severe consequences for human health. Diagnosis of Cu dyshomeostasis by assessment...
The continuous industrialization with the evolution of humankind and the rapidly increasing population have led to undesirable environmental changes due to anthropogenic activities, harming the environment, especially the aquatic ecosystem. The constant discharge of different toxicogenic entities in the aquatic ecosystem globally poses one of the most significant risks to living organisms, causing virulent diseases and even death. With technological advancements, the urgent demand for pure water devoid of harmful toxins and having a sustainable ecosystem have become paramount concerns. Among the various technologies, electrospinning, which is an efficient and facile method of fabrication, has received significant attention from various research domains, especially in wastewater treatment. This is ascribed to the enhanced efficacy, structural properties, and augmented performance of the fabricated nanostructured geometry, presenting a new facet of nanotechnology. Currently, although various techniques are applied for the fabrication of materials for wastewater treatment, the electrospinning of biopolymers is emerging as a sustainable fabrication system for effluent treatment, which exhibit the advantages of biodegradability (∼ at 9–32 °C in seawater), accessibility, porosity (∼80–90%) and biocompatibility. In the present review, we comprehensively investigate different toxins and their hazardous and prevailing effects on living species, and the advantages and application of various electrospun biopolymers for effluent removal. Also, we highlight the different mechanisms, the application of biopolymers in sorption, and the kinetics and isotherms associated with fabricated nanofibers for a better understanding of electrospun biopolymers as adsorbents.
Copper is a transition metal with the symbol Cu and atomic number 29. It is an essential trace element in all known organisms and is found in all human body tissues, with the highest concentrations measured in the liver and brain [1]. Cu is mostly present in biological systems as cupric form (Cu++), although several distinct types of the bound cation can be found in Cu-containing enzymes, often in combination within a single protein. Nearly two-thirds of the body Cu content (80–120 mg) are located in muscle and skeleton, but studies with isotopes have shown that the liver is a principal site in maintaining plasma cu concentrations [2].
Liver cells respond to copper loading upregulating protective mechanisms. However, to date, except for liver content,there are no good indicators that identify individuals with excess liver copper. We hypothesized that administering highdoses of copper to young (5.5 mg Cu × kg21 . d21) and adult (7.5 mg Cu × kg21 . d21) capuchin monkeys would inducedetectable liver damage. Study groups included adult monkeys (2 females, 2 males) 3–3.5 y old at enrollment treated withcopper for 36 mo (ACu); age-matched controls (1 female, 3 males) that did not receive additional copper (AC); youngmonkeys (2 female, 2 males) treated from birth with copper for 36 mo (YCu); and young age-matched controls (2 female, 2males) that did not receive additional copper (YC). We periodically assessed clinical, blood biochemical, and liverhistological indicators and at 36 mo the hepatic mRNA abundance of MT2a, APP, DMT1, CTR1, HGF, TGFb, and NFk onlyin adult monkeys. After 36 mo, the liver copper concentration was 4–5 times greater in treated monkeys relative tocontrols. All monkeys remained healthy with normal routine serum biochemical indices and there was no evidence of livertissue damage. Relative mRNA abundance of HGF, TGFb and NFkB was significantly greater in ACu than in AC monkeys.In conclusion, capuchin monkeys exposed to copper at doses up to 50 times the current upper level enhanced expressionof genes related to inflammation and injury without clinical, blood biochemical, or histological evidence of liverdamage
(15) (PDF) Chronic copper toxicity in a nonhuman primate model: Preliminary results. Available from: https://www.researchgate.net/publication/284072579_Chronic_copper_toxicity_in_a_nonhuman_primate_model_Preliminary_results [accessed Jul 18 2023].
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Copper metabolismWilson's disease (WD, McKusick277900)Non-Wilsonian copper-related cirrhosis in childhood
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.
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.
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.‖
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)
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)
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.
Copper—cessential but toxicCopper metabolismNormal valuesWilson's disease (OMIM 277900)Non-Wilsonian copper-related cirrhosis in childhoodReferences
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.
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.
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.
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.
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.
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)
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.
The principal iron uptake system of Saccharomyces cerevisiae utilizes a reductase activity that acts on ferric iron chelates external to the cell. The FRE1 gene product is required for this activity. The deduced amino acid sequence of the FRE1 protein exhibits hydrophobic regions compatible with transmembrane domains and has significant similarity to the sequence of the plasma membrane cytochrome b558 (the X-CGD protein), a critical component of a human phagocyte oxidoreductase, suggesting that FRE1 is a structural component of the yeast ferric reductase. FRE1 mRNA levels are repressed by iron. Fusion of 977 base pairs of FRE1 DNA upstream from the translation start site of an Escherichia coli lacZ reporter gene confers iron-dependent regulation on expression of beta-galactosidase in yeast. An 85-base-pair segment of FRE1 5' noncoding sequence contains a RAP1 binding site and a repeated sequence, TTTTTGCTCAYC; this segment is sufficient to confer iron-repressible transcriptional activity on heterologous downstream promoter elements.
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.
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.
The daily intakes for eight age-sex groups (infants, young children, and male and female teenagers, adults, and older adults) of nine nutritional elements (sodium, potassium, calcium, phosphorus, magnesium, iron, zinc, copper, and manganese) were obtained by laboratory analysis of the Food and Drug Administration's 234 Total Diet Study (TDS) foods and by use of the USDA Nutrient Data Base for Standard Reference. Food substitutions were required for eight TDS foods that had no direct counterparts in the USDA database. When corrections were made for missing values for magnesium, zinc, copper, and manganese in the USDA database, average percent differences between the two methods (USDA-TDS) for the age-sex groups were -2.6 for iron, 0.6 for manganese, 0.9 for zinc, 5 for potassium and phosphorus, 7 for magnesium, 8 for sodium and calcium, and 11.0 for copper. Data in the USDA database (when corrected for missing values) provided estimates of daily intakes of nine nutritional elements that were similar to those obtained by use of data from laboratory analysis in the TDS.