Intake Of Cu Research Articles

Mitochondrial miR-12294-5p-Regulated Copper Exposure-Caused Mitochondrial-Dependent Ferroptosis by Targeted Inhibition of CISD1 in Chicken Hepatocytes.

Copper (Cu) is a common trace element additive in animal and human foods, and excessive intake of Cu has been shown to cause hepatotoxicity, but the underlying mechanism remains unclear. Our previous research found that Cu exposure dramatically upregulated mitochondrial miR-12294-5p expression and confirmed its targeted inhibition of CISD1 expression in chicken hepatocytes. Thus, we aimed to explore the potential role of mitomiR-12294-5p/CISD1 axis in Cu exposure-resulted hepatotoxicity. Here, we observed that Cu exposure resulted in Cu accumulation and pathological injury in chicken livers. Moreover, we found that Cu exposure caused mitochondrial-dependent ferroptosis in chicken hepatocytes, which were prominent on the increased mitochondrial Fe2+ and mitochondrial lipid peroxidation, inhibited levels of CISD1, GPX4, DHODH, and IDH2, and also enhanced level of PTGS2. Notably, we identified that inhibition of mitomiR-2954 level effectively mitigated Cu-exposure-resulted mitochondrial Fe2+ accumulation and mitochondrial lipid peroxidation and prevented the development of mitochondrial-dependent ferroptosis. However, increasing the mitomiR-12294-5p expression considerably aggravated the influence of Cu on these indicators. Meanwhile, the overexpression of CISD1 effectively alleviated Cu-caused mitochondrial-dependent ferroptosis, while silent CISD1 eliminated the therapeutic role of mitomiR-12294-5p inhibitor. Overall, our findings indicated that mitomiR-12294-5p/CISD1 axis played a critical function in Cu-caused hepatotoxicity in chickens by regulating mitochondrial-dependent ferroptosis.

Copper in Commercial Marine Fish: From Biomonitoring to the ESG (Environment, Social, and Governance) Method

The presence of potentially harmful metals in commercially available saltwater fish has been extensively documented in scientific literature. This has demonstrated the significance of monitoring the crucial copper (Cu) levels in fish fillets from a perspective focused on human health risks (HHR). This study aimed to evaluate the human health risk (HHR) associated with the presence of Cu in 40 different species of commercial marine fish purchased from Malaysia. The fish samples were gathered from various sources from April to May 2023. The 40 species of commercial marine fish had concentrations of Cu (0.72–82.3 mg/kg dry weight) that fell below acceptable levels defined by seafood safety recommendations. Therefore, these fish are considered good sources of the essential element. The target hazard quotient values for Cu were below 1, suggesting that the hazards of Cu from fish eating are non-carcinogenic. Furthermore, it was discovered that the computed values for the predicted weekly consumption were lower than the defined provisional tolerated weekly intake of Cu. Consuming fish purchased from Malaysia is unlikely to harm consumers’ necessary copper intake. However, it is crucial to consistently monitor the safety of consumers who heavily depend on commercially caught marine fish from Malaysia. This monitoring is an essential aspect of implementing environmental, social, and governance (ESG) practices, which industries are concerned about and report on annually.

Factors Affecting Dietary Intake of Copper and Zinc via Rice Consumption by Residents of Major Rice-Producing Regions in China

Background: Copper (Cu) and zinc (Zn) are essential nutrients that must be maintained at adequate levels in the human body in order to make physiological functions normal and sustainable. Rice is a leading staple cereal crop which can be the main source of Cu and Zn in the diet. Results: Here, we aimed to investigate Cu and Zn concentrations in rice with corresponding soil influencing factors and to assess the dietary intake of Cu and Zn from rice consumption by residents of major rice producing regions. A total of 712 rice grain and 90 paired soil–rice samples were collected from September to November 2015 covering eleven provinces across China. Average Cu and Zn concentrations were 27.2 and 69.1 mg kg−1, respectively, in soils, and 1.98 and 12.3 mg kg−1 in rice. The concentrations and bioconcentration factors (BCFs) of Cu and Zn followed the sequence: roots > shoots > grains. Soil pH, cation exchange capacity (CEC), and soil organic carbon (SOC) play important roles in rice Cu and Zn uptake with negative effects. The average Cu and Zn intakes from rice consumption were 0.597 and 3.68 mg day−1, respectively. Conclusions: The status of Cu and Zn daily intake from rice consumption were fully adequate but there remained some sampling sites where Zn intake for males and Cu intakes were deficient at 1.40%, indicating that local residents need to maintain their dietary nutrient requirements.

Toxicity, physiological, and morphological alterations of Indian camphorweed (Pluchea indica) in response to excess copper.

Indian camphorweed (Pluchea indica (L.) Less.) is used as herbal tea due to the presence of volatile aromatic oils and several phytochemical compounds. The aim of this study was to assess the impact of copper (Cu) contamination on the physiology and morphology of P. indica, and the health risks associated with its consumption as tea. The cuttings of P. indica were subjected to 0mM (control), 5mM (low Cu), and 20mM (excess Cu) of CuSO4 treatments for 1, 2, and 4weeks. Thereafter, Cu contamination as well as physiological and morphological parameters were assessed. Cu accumulation was higher in the root tissues of plants (25.8 folds higher as compared to the leaves) grown under 20mM CuSO4 for 4weeks. This increased Cu accumulation resulted in the inhibition of root length, root fresh weight, and root dry weight. Cu concentration was found maximum (1.36μgg-1 DW) in the leaf tissues under 20mM Cu exposure for 4weeks, with the highest target hazard quotient (THQ = 1.85), whereas Cu was not detected in control. Under exposure to 20mM Cu treatment for 4weeks, leaf greenness, maximum quantum yield of photosystem II, and photon yield of photosystem II diminished by 21.4%, 16.1%, and 22.4%, respectively, as compared to the control. Leaf temperature was increased by 2.5°C, and the crop stress index (CSI) exceeded 0.6 when exposed to 20mM Cu treatment for 2 and 4weeks; however, the control had a CSI below 0.5. This led to a reduced transpiration rate and stomatal conductance. In addition, the net photosynthetic rate was also found sensitive to Cu treatment, which resulted in decreased shoot and root growth. Based on the key results, it can be suggested that P. indica herbal tea derived from the foliage of plants grown under a 5mM Cu level (0.75μgg-1 DW) with a target hazard quotient below one aligns with the recommended dietary intake of Cu in leafy vegetables. The study recommends choosing cuttings from plants with a small canopy as plant material in the greenhouse microclimates to validate the growth performance in the Cu-contaminated soil and simulate the natural shrub architecture and life cycle.

Limited impacts of high doses of dietary copper on the gut bacterial metal resistome explain negligible co-selection of antibiotic resistance

High dietary intake of Cu has previously been linked to the selection of Cu resistance and co-selection of antibiotic resistance in specific gut bacteria. Based on a novel HT-qPCR metal resistance gene chip as combined with 16S rRNA gene amplicon sequencing and phenotypic resistance typing of Escherichia coli isolates, we here report the impacts of two contrasting Cu-based feed additives on the swine gut bacterial metal resistome and community assembly. DNA was extracted from fecal samples (n = 80) collected at day 26 and 116 of the experiment from 200 pigs allotted to five dietary treatments: negative control (NC) diet with 20 μg CuSO4 g−1 and four diets added 125 or 250 μg CuSO4 g−1 feed or 125 or 250 μg Cu2O g−1 feed to the NC diet. Dietary Cu supplementation reduced the relative abundance of Lactobacillus, but it had negligible impacts on bacterial community composition relative to the gut microbiome maturation effect (time). The relative importance of different bacterial community assembly processes was not markedly affected by the dietary Cu treatments, and differences in swine gut metal resistome composition could be explained primarily by differences in bacterial community composition rather than by dietary Cu treatments. High dietary Cu intake (250 μg Cu g−1) selected for phenotypic Cu resistance in E. coli isolates, but surprisingly it did not result in increased prevalence of the Cu resistance genes targeted by the HT-qPCR chip. In conclusion, the lacking impacts of dietary Cu on the gut bacterial metal resistome explain results from a previous study showing that even high therapeutic doses of dietary Cu did not cause co-selection of antibiotic resistance genes and mobile genetic elements known to harbor these genes.

Sensitive detection and intracellular imaging of free copper ions based on DNA-templated silver nanoclusters aggregation-inducing fluorescence enhancement effect

Free copper ions (Cu+ and Cu2+) have critical toxicity to cells, although copper is an essential element for human body. Hence, sensitive monitoring is crucial to avoid over intake of Cu+/Cu2+. We herein designed a ssDNA sequence (A31) for synthetizing A31-templated silver nanoclusters (AgNCs), and demonstrated that Cu+/Cu2+ can induce the aggregation of A31-templated AgNCs and thus greatly enhanced the fluorescence emission of A31-templated AgNCs. Based on Cu+/Cu2+-induced fluorescence enhancement effect of A31-templated AgNCs, a label-free and signal-on fluorescent sensing platform was developed for the specific and sensitive detection of Cu+/Cu2+ in biological samples and intracellular imaging of Cu+/Cu2+ in cells. The signal-on fluorescent sensing platform could be used to rapidly detect Cu+ and Cu2+ with a detection limit of 0.1 µM within 30 min., and to perform the intracellular imaging of Cu+ and Cu2+ in cells with good cell permeability and biocompatibility. By using the signal-on fluorescent sensing platform, we have successfully detected Cu+ and Cu2+ in cells fluids and human serum with a recovery of 90–104% and a RSD (n = 5) < 5%, and performed the imaging of Cu+/Cu2+ in Hela cells. The developed fluorescent sensing platform has obvious analytical and imaging advantages such as signal-on, simple operation, short analysis time, both Cu+ and Cu2+ detection, similar or higher sensitivity, good cell permeability and biocompatibility, which promising a reliable approach for the rapid and on-site detection or imaging of free copper ions in biological samples in clinical diagnosis.

Zirconium based metal-organic framework for the adsorption of Cu (II) ions in real water samples

Copper (II) is one of the most abundant heavy metal ions commonly found in water resources from industrial effluents discharge. Subsequently, it contaminates the food chain and becomes a source of toxicity to human beings and the entire ecological system. High intake of Cu (II) causes serious health effects and even death. The amino acid ligands possess high interaction towards metal ions. To efficiently remove Cu (II) ions from wastewater, we designed and prepared an eco-friendly Zirconium-based Metal-Organic Framework (Zr-MOF) using solitary amino acid (L-tyrosine) as ligand via a simple solvothermal method. The Zr-MOF is partially amorphous, strong solid with a thermal stability of 180 °C. The Zr-MOF has a surface area of 295 m2 g−1, wide pore size distribution ranges from 0.2 to 1.2 nm, with a pore volume of 0.6 cm3 g−1, which can easily trap the Cu (II) ions. Cu (II) ions adsorption analyses are carried out using a simple one-step method (UV Visible Spectroscopy) over other complicated experiments and equations. Zr-MOF exhibits adsorptive behavior on Cu (II) ions from water under any pH range from 1 to 13. The newly developed adsorption technique iss successfully employed to remove Cu (II) with an average adsorption capacity (qe) of Zr-MOF is 79.34 mg g−1 (maximum: 125 mg g−1) and a maximum Cu (II) ion removal efficiency (R) of Zr-MOF is found as 50% (average: 31.7%) in real water samples. This amino acid ligated MOF synthesis will open the doors towards biocompatible MOF development for the environmental remediation applications.

CuO nanoparticles in irrigation wastewater have no detrimental effect on rice growth but may pose human health risks

The possibility of metal-based nanoparticles (NPs) being released into agricultural soils via sewage systems has raised widespread concern about their negative effects on crop plants, soils, and potential risks to human health via the food chain. The objectives of this study were to (i) determine the effect of CuO NPs in irrigation water on plant growth and Cu accumulation in a rice–soil system using continuous sub-irrigation with treated wastewater (CSI), and (ii) assess the Cu exposure and potential health risk associated with rice consumption. CuO NPs were examined in treated municipal wastewater (TWW) at environmentally acceptable concentrations (0, 0.02, 0.2, and 2.0 mg Cu L−1), allowing for effluent discharge and/or crop irrigation reuse. Low CuO NP concentrations in TWW had no adverse effect on plant growth, yield, or grain quality. Cu accumulation significantly increased in various parts of rice plants and paddy soils at 2.0 mg Cu L−1. CuO NPs had no discernible effect on rice plants when compared to CuSO4 at 0.2 mg Cu L−1. The estimated daily intake of Cu derived from inadvertent consumption of Cu-contaminated rice (by CuO NPs in TWW) for young children aged 0–6 years exceeded the oral reference dose for toxicity. Overall, we found no acute toxicity of CuO NPs in TWW to rice plants, but significant Cu accumulation in grains. This implies that there is a high risk of human health problems associated with rice that was intensively irrigated with TWW containing CuO NPs.

Effects of Long-Term Exposure to Copper on Mitochondria-Mediated Apoptosis in Pig Liver.

Copper (Cu) is listed as one of the main heavy metal pollutants, which poses potential health risks to humans. Excessive intake of Cu has shown toxic effects on the organs of many animals, and the liver is one of the most important organs to metabolize it. In this study, pigs, the mammal with similar metabolic characteristics to humans, were selected to assess the effects of long-term exposure to Cu on mitochondria-mediated apoptosis, which are of great significance for studying the toxicity of Cu to humans. Pigs were fed a diet with different contents of Cu (10, 125, and 250mg/kg) for 80days. Samples of blood and liver tissue were collected on days 40 and 80. Experimental results demonstrated that the accumulation of Cu in the liver was increased in a dose-dependent and time-dependent manner. Meanwhile, the curve of pig's body weight showed that a 125mg/kg Cu diet promoted the growth of pigs during the first 40days and then inhibited it from 40 to 80days, while the 250mg/kg Cu diet inhibited the growth of pigs during 80days of feeding. Additionally, the genes and protein expression levels of Caspase-3, p53, Bax, Bak1, Bid, Bad, CytC, and Drp1 in the treatment group were higher than that in the control group, while Bcl-2, Bcl-xL, Opa1, Mfn1, and Mfn2 were decreased. In conclusion, these results indicated that long-term excessive intake of Cu could inhibit the growth of pigs and induced mitochondria-mediated apoptosis by breaking the mitochondrial dynamic balance. Synopsis: Long-term exposure to high doses of Cu could lead to mitochondrialdysfunction by breaking the mitochondrial dynamic balance, which ultimatelyinduced mitochondria-mediated apoptosis in the liver of pigs. This might be closelyrelated to the growth inhibition and liver damage in pigs.

Toxicological mechanism of large amount of copper supplementation: Effects on endoplasmic reticulum stress and mitochondria-mediated apoptosis by Nrf2/HO-1 pathway-induced oxidative stress in the porcine myocardium

Copper (Cu) is an essential micronutrient that is required by all living organisms. However, Cu can also be a potentially toxic metal if excessive dietary supplementation occurs. The current study aimed to investigate the mechanism of Cu toxicity in the cardiomyocytes of large mammal pigs. Here, we used pigs to explore Cu toxicity in the control group (10 mg/kg Cu) and treatment groups (125 mg/kg and 250 mg/kg Cu) for a period of 80 days. Consequently, we identified that large amount intake of Cu led to in oxidative damage, and activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)-mediated antioxidant pathway, indicating an imbalanced redox status in the myocardium. Furthermore, Cu exposure activated endoplasmic reticulum (ER) stress through upregulating levels of glucose-regulated protein 78 (GRP78), c-Jun N-terminal kinase (JNK), glucose-regulated protein 94 (GRP94), X-box binding protein 1 (XBP1), and C/EBP homologous protein (CHOP). Additionally, mitochondrial fission and fusion homeostasis was disrupted and the copy number of mitochondrial DNA (mtDNA) was reduced under Cu exposure. Furthermore, Cu exposure could induce apoptosis, evidenced by the increased terminal deoxynucleotidyl transferase biotin-d UTP nick end labeling (TUNEL)-positive staining, the upregulated expression levels of Cytoplasm-cytochrome C (Cytc), Bcl-2-associated X protein (Bax), and Cleaved-caspase3, and decreased expression level of B-cell lymphoma-2 (Bcl-2) and Mitochondrial-cytc. In summary, large amount of Cu could trigger Nrf2/HO-1 pathway-mediated oxidative stress, which promotes ER stress and mitochondrial damage pathways, causing apoptosis in cardiomyocytes.

Copper and Zinc Levels in Commercial Marine Fish from Setiu, East Coast of Peninsular Malaysia.

Potentially toxic metals (PTMs) in edible marine fish have been widely reported from at least 15 different regions or countries in the literature. This evidently demonstrates the importance of monitoring the PTMs in fish fillets from a human health risk (HHR) point of view. This study aims to assess the HHR of Cu and Zn in 19 species of marine fish from popular marine fish loading sites at Setiu in Terengganu, on the east coast of Peninsular Malaysia, collected between August 2016 and February 2017. With overall ranges of concentrations (mg/kg dry weight) of Cu (1.50–7.83), and Zn (24.1–80.5), the 19 species of marine fishes from Setiu are good sources of these essential elements because they are below the maximum permissible limits set by seafood safety guidelines. The target hazard quotient values of Cu and Zn were lower than one, indicating non-carcinogenic risks of Cu and Zn in fish consumption. It was also found that the calculated values of the estimated weekly intake were below the established provisional tolerable weekly intake of Cu and Zn. It can be concluded that the consumption of fish from Setiu would not pose adverse effects from the PTMs to consumers. Nonetheless, continuous monitoring is necessary to ensure the safety of consumers who rely heavily on marine fish in Setiu coastal waters.

Carpet industry irrigational sources risk assessment: Heavy metal contaminated vegetables and cereal crops in northern India

Wastewater is often discharged to natural water bodies through an open channel as well as used by marginal farmers to irrigate the agricultural fields, particularly in sub-urban areas of developing countries. In the present study, the samples of irrigation water, soil, vegetables (i.e., palak; Beta vulgaris L. var All green H1, radish; Raphanus sativus L., garlic; Allium sativum L., cabbage; Brassica oleracea L. var. capitata, brinjal; Solanum melongena L.) and crops (i.e., paddy; Oryza sativa L. and wheat; Triticum aestivum L.) were collected from the agricultural areas receiving untreated wastewater from a carpet industrial and residential areas since a decade. The contents of Cd, Cr, Cu, Ni, and Zn in the filtrates of water, soil, and crops were determined using an Atomic Absorption Spectrophotometer (Perkin-Elmer AAnalyst 800, USA). Daily intake, hazardous quotient and heavy metal pollution index were computed to assess the health risk associated with consumption of heavy metal contaminated crops. The mean concentrations of Cd and Zn in B. vulgaris (5.35 µg g−1 dw and 58.41 µg g−1 dw, respectively) and Cr, Cu, and Ni in grains of T. aestivum (16.02 µg g−1 dw, 27.97 µg g−1 dw and 40.74 µg g−1 dw, respectively) were found highest and had exceeded the Indian safety limit. Daily intake of Cu, Ni, and Cr via consumption of tested cereal crops was found higher than the vegetables. The health quotient revealed that health of local residents is more linked to vegetables than cereal crops. The present findings may be helpful to the policymakers and regulatory authorities to modify the existing policy of wastewater uses in the agriculture and disposal to the natural water bodies. The regular monitoring of heavy metals in the wastewater should also be ensured by the regulatory authorities for their safe disposal to natural water bodies/agriculture in order to reduce the human health risk associated with the degree of heavy metal contaminated suburban food systems.

Intake of divalent copper and nickel onto natural zeolite from aqueous solutions: a study in mono- and dicomponent systems.

In this study, the noncompetitive and competitive adsorption process of copper (II) and nickel (II) ions on the natural zeolite were examined in simulated wastewater in a batch system with respect to concentration, pH and temperature. Optimum pH values were found as 5,0 for adsorption of copper and nickel ions on the zeolite. The effect of initial concentration and ambient temperature on the yield of adsorption was examined at this pH value. The equilibrium adsorption data of Cu (II) and Ni (II) onto the zeolite were analyzed by the Langmuir's and Freundlich's isotherms, and the experimental metal uptake data fitted well with both isotherm models. In case of the presence of simultaneous multimetal ions in the aqueous phase, the adsorption capacity of the adsorbent is slightly low probably due to the competitive uptake of each metal ion by the adsorbent. For the metal sorption system, the negative Gibbs free energy values show the applicability and spontaneous nature of the metal uptake treatment by the zeolite. The activation energy and enthalpy change of divalent cation adsorption demonstrate that the intake of Cu (II) and Ni (II) onto the zeolite involves not only a chemical adsorption process but also a physical adsorption process.

Copper exposure induces mitochondrial dynamic disorder and oxidative stress via mitochondrial unfolded protein response in pig fundic gland

Cu is a metallic element that widely spread over in the environment, which have raised wide concerns about the potential toxic effects and public health threat. The objective of this study aimed to investigate the impression of copper (Cu)-triggered toxicity on mitochondrial dynamic, oxidative stress, and unfolded protein response (UPRmt) in fundic gland of pigs. Weaned pigs were randomly distributed into three groups, fed with different Cu of 10 mg/kg (control group), 125 mg/kg (group I), and 250 mg/kg (group Ⅱ). The trial persisted for 80 days and the fundic gland tissues were collected for further researches. Moreover, the markers participated to mitochondrial dynamic, UPRmt，and oxidative stress in fundic gland were determined. Results revealed that vacuolar degeneration were observed in the treated groups contrast with control group, and the Cu level was boosted with the increasing intake of Cu. Besides that, the levels of CAT, TRX, H2O2, and G6PDH were reduced in group Ⅰ and group Ⅱ, the mRNA levels of NRF2, HO-1, SOD-1, CAT, SOD-2, GSR, GPX1, GPX4, and TRX in the treated groups were promoted contrast to control group. Furthermore, the protein expression of KEAP1 was dramatically decreased, and the protein expression of NRF2, TRX and HO-1 were markedly enhanced in group Ⅰ and Ⅱ at 80 days. Moreover, the mRNA and protein expression levels of MFN1, MFN2, and OPA1 down-regulated and protein level of DRP1 was increased with the adding levels of Cu. Nevertheless, the UPRmt-related mRNA levels of CLPP, HTRA-2, CHOP, HSP10, and HSP60 were enhanced dramatically in Cu treatment group compared with control group. In general, our current study demonstrated that excessive absorption of Cu in fundic gland were related with stimulating UPRmt, oxidative stress, and the NRF2 interceded antioxidant defense. These results could afford an updated evidence on molecular theory of Cu-invited toxicity.

Dietary Metals (Pb, Cu, Cd, Zn) Exposure and Associated Health Risks in Baia Mare Area, Northwestern Romania

This study estimated the non-carcinogenic health risk of Pb, Cu, Cd, Zn via dietary intake in the urban and rural areas of Baia Mare city, northwestern Romania, a former mining area. A total of 230 food items grouped in ten food categories (meat and animal organs, meat-derived products, animal fat, eggs, dairy, bread, corn flour, potato, vegetables, fruits) and 32 water samples were collected and analyzed for Pb, Cu, Cd and Zn using atomic absorption spectrometric method. The human health risk assessment through dietary exposure was evaluated by calculating the estimated daily intake of metals, the Target Hazard Quotients (THQ) and the Total Target Hazard Quotients (TTHQ) for normal daily consumption in adults. The average daily intakes of Pb, Cd and Zn were higher than the Tolerable Daily Intake (TDI) reference value for urban and rural residents, which showed that there was a potentially high risk of ingestion of food and water. The average daily intake of Cu with food and drinking water was lower than the corresponding TDI value, which indicated that Cu intake was not a potential hazard to the health of residents in the study areas. The individual target hazard quotients, calculated for food consumption in urban area decreased in the following order: Cd&gt;Cu&gt;Pb&gt;Zn, and in rural area: Pb&gt;Cd&gt;Cu&gt;Zn, having values higher than 1 for Pb and Cd in the rural area and approximately equal to 1 for Cd (urban) and Cu (rural), indicating non-carcinogenic adverse health effects. The TTHQs for the two areas (urban and rural) were 2.934 and 5.164, respectively, established cumulative adverse effects of metals. The results showed that vegetables, potato and bread were the main sources of metal intake from foodstuff for adults, but fruit, water and meat were secondary contributors.

Dietary copper and selenium are associated with insulin resistance in overweight and obese Malaysian adults

Imbalance in or inadequate intake of micronutrients may impair insulin synthesis, secretion, and it's signaling pathways. This study aimed to investigate the associations between dietary copper (Cu) and selenium (Se) with insulin resistance (IR), in overweight/obese adults. We hypothesized that dietary Cu and Se are associated with IR in a non-linear trend. A cross-sectional study was conducted on 128 non-diabetic overweight and obese Malaysian adults aged ≥18 years with a body mass index ≥23 kg/m2. Dietary intake was assessed using food frequency questionnaire. IR was defined as homeostatic model assessment-insulin resistance (HOMA-IR) ≥1.7. Locally weighted scatterplot smoothing regression was performed to detect non-linearity and piecewise regression models were computed to examine the trend of the associations at different cut off points. In this study, 45% (n = 57) of the study participants were found to be insulin resistant. A U-shaped non-linear relation between Se and HOMA-IR was observed. Three-piecewise regression models revealed positive association between Se and HOMA-IR in individuals with relatively low (<0.3 µg/kg/d) and high (≥1.01 µg/kg/d) intake of Se (β coefficient = 3.835, CI = -12.216 to 19.886, P= 0.614; and β coefficient = 0.785, CI = 0.386-1.185, P = 0.014, respectively). Significant positive association was only found between dietary Cu and HOMA-IR with intake of Cu ≥ 13.4 µg/kg/d, 0.276 (CI = 0.025-0.526; P = 0.033). In conclusion, our findings reveal that a critical balance in the dietary intake of copper and Se is crucial for health, more so in insulin resistant and diabetic individuals. In the latter treatment should include measured intake of both copper and Se, personalized according to individual habitual food preferences and intakes.

Copper Induces Spleen Damage Through Modulation of Oxidative Stress, Apoptosis, DNA Damage, and Inflammation.

Copper (Cu) is an essential micronutrient for both humans and animals; however, excessive intake of Cu can be immunotoxic. There are limited studies on spleen toxicity induced by Cu. This study was conducted to investigate the effects of Cu on spleen oxidative stress, apoptosis, and inflammatory responses in mice orally administered with 0 mg/kg, 10 mg/kg, 20 mg/kg, and 40 mg/kg of CuSO4 for 42 days. As discovered in this work, copper sulfate (CuSO4) reduced the activities of antioxidant enzymes (SOD, CAT, and GSH-Px), decreased GSH contents, and increased MDA contents. Meanwhile, CuSO4 induced apoptosis by increasing TUNEL-positive cells in the spleen. Also, CuSO4 increased the expression of γ-H2AX, which is the marker of DNA damage. Concurrently, CuSO4 caused inflammation by increasing the mRNA levels of interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-12, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). In conclusion, the abovementioned findings demonstrate that over 10 mg/kg CuSO4 can cause oxidative stress, apoptosis, DNA damage, and inflammatory responses, which contribute to spleen dysfunction in mice.

Human Health Risk Assessment of Heavy Metals Through the Consumption of Common Foodstuffs Collected from Two Divisional Cities of Bangladesh

This study was designed to evaluate heavy metal status in commonly consumed foodstuffs collected from two divisional cities, viz., Chottogram and Mymensingh of Bangladesh and to assess potential human health risks through the consumption of those foodstuffs. A total of 90 food samples were analyzed for Cu, Zn, Ni, Pb, Mn, and Fe contents by an atomic absorption spectrophotometer. The calculated per capita per day dietary intakes of Cu and Mn from rice and Mn’s same value through spinach consumption in both cities were higher than the recommended daily allowances (RDA) for an adult human. Similarly, the computed daily metal intake (DMI) values of Pb for both males and females were also higher than the upper tolerable intake level (UTIL) through the consumption of rice collected from Mymensingh city. The average calculated hazard index (HI) values for males and females due to dietary intake of rice were 47.67 and 93.30 in Chottogram city and 97.98 and 192.04 in Mymensingh city, respectively. The present study identified rice as the most contaminated food item, followed by spinach, brinjal, and lentil. Still, dietary intakes of beef, broiler, and fish samples collected from both the cities were found as safe or less hazardous. Among the individual metals, Mn was the most dominant metal present in different foodstuffs collected from both the cities and contributed significant risk to the people. Finally, the study concluded that Bangladesh’s food consumption patterns should be changed and advised to incorporate more proteins in regular diet charts by reducing carbohydrates.

Copper induces hepatocyte autophagy via the mammalian targets of the rapamycin signaling pathway in mice

Although copper is among the indispensable trace elements in animal physiological processes, it exerts toxicity upon over-exposure. The present study aimed to investigate hepatocyte autophagy induced by CuSO4 and its potential mechanism. A total of 240 ICR mice (four-week-old, 120 males and 120 females) were randomly divided into four groups, in which mice separately received 0, 4, 8, and 16 mg/kg of Cu (Cu2+-CuSO4) for 42 d. The results of increased autophagosomes and autophagy marker LC3B brown cell staining showed that excessive intake of Cu enhanced hepatocyte autophagy. Simultaneously, Cu inhibited the activity of mTOR through suppressing mRNA and protein expressions in mTOR, which in turn up-regulated expression levels of ULK1 and initiated autophagy. Also, over-exposure to Cu increased mRNA and protein expressions of Beclin1, Atg12, Atg5, Atg16L1, Atg7, Atg3, and LC3 and decreased mRNA and protein expressions of p62. These results indicate that excess Cu can enhance hepatocyte autophagy via inhibiting the mTOR signaling pathway and regulating mRNA and protein expressions of factors implicated to autophagy in mice.

Evaluation of the association between the healthy eating index and the level of serum and dietary intake of copper and zinc

BackgroundHealthy behaviors, such as a healthy diet are associated with a reduced risk of several chronic diseases. We aimed to investigate the association of dietary quality, assessed using the Healthy Eating Index (HEI), with serum copper (Cu) and zinc (Zn) and also dietary intake of Cu and Zn. Study designThis cross-sectional study was performed in a sub-sample of 5313 participants (2162 males and 3151 females) aged 35–65 years recruited as part of MASHAD cohort study. MethodsHEI was assessed using dietary intake data that were collected based on a 65 items food frequency questionnaire (FFQ). Flame atomic absorption spectrometry was used to measure serum Cu and Zn concentrations. Dietary intakes of Cu and Zn were evaluated based on the FFQ data; they were adjusted for total energy. ResultsHEI values had a negative correlation with serum Cu concentration and positive correlation with dietary intake and serum Zn/Cu showed. After adjusting for confounding factors, results showed that with increasing 10 unit of HEI the risk of serum level of Cu < 70 μg/dl (male)/<80 μg/dl (female) 1.09-fold increases in comparison to reference group (70–140 μg/dl [male]/80–155 μg/dl [female]). Moreover, after adjusting for confounding factors, a significant association was found between serum Zn/Cu and HEI (β = 0.003; 95%CI = 0.002–0.005; p < 0.001) but this association was not significant for dietary intake Zn/Cu. ConclusionThere was a negative and positive correlation between HEI and serum concentration of Cu and serum Zn/Cu, respectively in the middle-aged Iranian adults. Although, the association between serum concentrations of Zn and Cu with their dietary intake were not significant. The evaluation of these factors in a larger population and in cohort study design may help further confirm these findings.