Serum Copper Concentrations Research Articles

Metal Exposure and Risk of Parkinson Disease: A Systematic Review and Meta-Analysis.

Metal exposure has been suggested as a possible environmental risk factor for Parkinson disease (PD). We searched the PubMed, EMBASE, and Cochrane databases to systematically review the literature on the relationship between metal exposure and PD risk and to examine the overall quality of each study and the exposure assessment method. A total of 83 case-control studies and 5 cohort studies published duringthe period 1963-July 2021 were included, of which 73 were graded as being of low or moderate overall quality. Investigators in 69 studies adopted self-reported exposure and biomonitoring after disease diagnosis for exposure assessment approaches. The meta-analyses showed that concentrations of copper and iron in serum and concentrations of zinc in either serum or plasma were lower, while concentrations of magnesium in CSF and zinc in hair were higher, among PD cases as compared with controls. Cumulative lead levels in bone were found to be associated with increased risk of PD. We did not find associations between other metals and PD. The current level of evidence for associations between metals and PD risk is limited, as biases from methodological limitations cannot be ruled out. High-quality studies assessing metal levels before disease onset are needed to improve our understanding of the role of metals in the etiology of PD.

Multitargeting Strategy Using Tetrathiomolybdate and Lenvatinib: Maximizing Antiangiogenesis Activity in a Preclinical Liver Cancer Model.

The study aims to investigate the suppressing tumor-promoting effects via multi-anti-angiogenesis activity of the copper chelator (ammonium tetrathiomolybdate, TM) combined with lenvatinib for hepatocellular carcinoma. A total of 55 C57 mice were injected subcutaneously with Hepa1-6 hepatoma cell suspensions into the right posterior thigh. After 7 days, the subcutaneous tumors were formed, and the mice were randomly divided into five groups: TM (G1), Lenvatinib (G2), TM+Lenvatinib (G3), Control (G4), and Copper (II) Gluconate (G5). The copper concentrations in serum and tumors were measured at the predetermined time points. After 14 days of treatments, tumor weight and volumes were analyzed, histology was observed, and the expressions of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in tumor tissues were measured by immunohistochemistry. The median concentration of copper in serum was 401.70, 469.40, and 665.35 μg/L in normal mice, in mice 7 days after implantation, and in the control group, respectively. The intratumoral copper concentrations were higher in G4 mice than in mice 7 days after implantation (P < 0.05). The serum concentration of copper was higher in G5 than all the other groups (P < 0.05; (G1, G2, and G3) vs. G4, P < 0.05; G1 vs. G2, P = 0.013; G2 vs. G3, P = 0.018; G1 vs. G3, P = 0.903. The intratumoral copper concentrations were 608.40, 980.00, 539.31, and 2938.90 μg/L in G1, G2, G3, and G5, respectively. The average tumor weight was 0.55, 0.44, 0.08, 1.37, and 3.11 in G1, G2, G3, G4, and G5, respectively. G5 vs. other groups, P < 0.05; (G1, G2, and G3) vs. G4, P < 0.05; G1 vs. G3, P < 0.05; G2 vs. G3, P < 0.05; G1 vs. G2, P > 0.05. Furthermore, the expression levels of VEGF were significantly lower in G1, G2, and G3 than in G4 and G5 (P < 0.05). A similar trend was observed for MVD in the five groups, but no significant difference was detected in G1 and G2. The study showed a significant positive correlation between tumor load and copper. Copper promotes tumor progression, but copper chelating suppresses tumor growth. The combination of TM with lenvatinib reduces tumor angiogenesis and improves the effect of antitumor treatment. These findings underlie the clinical application of combination therapy.

Serum concentration of zinc, copper, iron, and its associated factors among pregnant women of small-scale farming in western Ethiopia

Micro-nutrients are required in small amounts to maintain growth and cell functioning to complete the life cycle through reproductions. However, pregnant women in developing countries like Ethiopia are vulnerable to multiple micro-nutrient deficiencies. Therefore, this study aimed at assessing the serum level of metals and associated factors like dietary diversity, and health-related problems in pregnant women among small-scale farming in Kellem Wellega, western Ethiopia. A cross-sectional laboratory-based study was conducted from June to August 2021 on 417 pregnant women attending antenatal care at rural healthcare facilities. Data was collected by using per-tested structured questionnaires via face-to-face interviews. The data analysis was conducted using SPSS version 24.0, and multivariate logistic regression analysis was performed to determine the association between predictor and outcome variables. A statistically significant was considered at p value < 0.05 for all the analyses. Our study findings showed that 62.1, 80.9, and 71.9% of the participants were deficient in iron, zinc, and copper micro-nutrient levels, respectively. Pregnant women who could not have formal education were 3.24 (AOR = 3.24, 95% CI 1.33–7.91) and 3.98 (AOR = 3.98, 95% CI 1.2–13.15) times more likely to show zinc and copper deficiency than those who attended secondary school and above, respectively. Furthermore, pregnant women involved only in farming activities were 0.57 (AOR = 0.57, 95% CI 0.36–0.91) and 4.33 (AOR = 5.72, 95% CI 2.34–13.97) times more likely to be exposed to iron and zinc deficiency than those who were engaged in other activities. This study revealed that pregnant women with low income were 6.36 times more likely to be exposed to zinc micro-nutrient deficiencies than those with high-income participants (AOR = 6.36, 95% CI 1.47–27.61). Additionally, those participants who ate a varied diet between 1 and 4 items per day were 2.26 (AOR = 2.26, 95% CI 1.43–3.59) and 2.77 (AOR = 2.77, 95% CI 1.6–4.61) times more likely to suffer zinc and copper micro-nutrient insufficiency than those who consumed 5–10 items per day. Finally, pregnant women who developed diarrhea in the past three months were 1.82 (AOR = 2.77, 95% CI 1.14–2.92) and 2.52 (AOR = 2.52, 95% CI 1.3–4.91) times more likely to be exposed to iron and copper deficiency than those who never show the symptoms, respectively. This study identified low concentrations of zinc, iron, and copper in the blood serum of pregnant women of small-scale farmers.

Supplemental Dietary Cystine Elevates Kidney Metallothionein in Rats by a Mechanism Involving Altered Zinc Metabolism

Dietary sulfur-containing amino acids influence zinc and copper status. This study was conducted to investigate the relationship between the status of these elements and tissue metailothionein in rats fed diets supplemented with sulfur-containing amino acids. In a series of experiments, a diet containing 100 g casein/kg diet was unsupplemented or supplemented with L-cystine (3–50 g/kg diet) or L-methionine (3 or 30 g/kg diet). Kidney concentrations of zinc and copper in rats fed the diet supplemented with high levels of cystine (25 or 50 g/kg) were significantly higher than those in rats fed the unsupplemented diet. Kidney concentrations of metallothionein and metallothionein mRNA were also significantly higher in rats fed cystine-supplemented diets. There was a correlation (r = 0.838, P < 0.01) between the levels of zinc and metallothionein in kidney of rats fed the diets with different levels of cystine and zinc. However, in the rats fed the diets with different levels of cystine and copper, the correlation was not as strong (r = 0.587, P < 0.01). The changes in kidney metallothionein concentration due to the addition of 3 or 30 g/kg cystine were associated with parallel changes in serum zinc concentration and in apparent absorption of zinc, but not in serum copper concentration or apparent absorption of copper. Addition of 3 or 30 g methionine/kg diet to the diet did not affect kidney concentrations of metallothionein or zinc. These results indicate that supplementation of cystine to the diet can induce kidney metallothionein through a mechanism involving altered zinc metabolism.

Antioxidant system of the body of young Ukrainian beef cattle under the action of microelements

Active forms of oxygen are formed in the course of the organism's vital activity in biochemical reactions. These forms, when the pro/antioxidant balance is disturbed, trigger a cascade of lipid peroxidation, which can be the cause of the development of various pathological conditions. To prevent the negative influence of lipid peroxidation products in the body, a powerful antioxidant system is activated. This system consists of an enzymatic and a non-enzymatic link. An important aspect of the normal functioning of this system is the provision of the body with important trace elements. A number of minerals are included in the active center of antioxidant enzymes or have an effect on the reactions of non-enzymatic antioxidants. Research was conducted on fattening bulls of the Ukrainian meat breed. During the monitoring of microelements in feed, it was found that the vast majority of farm feed was deficient in copper, selenium and manganese and for this reason the animals consumed an insufficient amount of these minerals. These data were confirmed by the low content of these trace elements in blood serum. The addition of inorganic salts of microelements to the basic diet led to an increase in the concentration of copper, manganese and selenium in the blood serum by 20.5%, 37.3% and 23.9%. The study of the content of lipid peroxidation products showed that during the 30 days of the experiment, the level of lipid hydroperoxide increased by 25.5%, diene conjugates by 22.8%, and malonic dialdehyde by 22.0%. This indicates that against the background of increased age-related metabolism in the body of young animals, the oxidation-reduction reactions that are a predictor of the start of peroxidation processes increase. It was also noted that with a deficiency of certain trace elements, the activity of both the enzymatic and non-enzymatic links of the antioxidant system was reduced. Thus, in 30 days, the level of catalase, superoxide dismutase, and glutathione peroxidase decreased by 9.4%, 15.3%, and 13.0%, respectively. During this time, the content of tocopherol and ceruloplasmin decreased by 16.8% and 9.8%. Additives also had a positive effect on the activity of the antioxidant system by increasing its components. Additives of trace elements had different effects on the activity of antioxidant enzymes. The greatest effect on the level of catalase and superoxide dismutase was observed when copper salts were added, when the increase of these enzymes was noted by 1.11 and 1.23 times, respectively. Accordingly, the level of glutathione peroxidase was the highest in animals that received additional selenium – 1.21 times. The addition of copper also had the greatest biological effect on the important non-enzymatic component of antioxidant protection – ceruloplasmin. Its level increased by 1.24 times under the action of copper sulfate. The level of tocopherol was higher under the action of manganese, when its concentration was 1.11 times higher than the control. Against this background, there was a decrease in the products of lipid peroxidation: lipid hydroperoxides – 1.19 times under the action of selenium; diene conjugates – by 1.22 times and malonіс dialdehyde – by 1.11 times under the influence of copper and manganese compounds, respectively.

The Association of Serum Elements’ Levels with the Severity of Pulmonary Involvement in Cystic Fibrosis Patients

Background: Cystic fibrosis (CF) is a multisystem disease presenting different manifestations, including the involvement of the respiratory and gastrointestinal tract. Patients may be at risk for micronutrient depletion, particularly during illness and infection. However, the relationship between micronutrient depletion and pulmonary involvement is not established well. Objectives: This study aimed to determine the relationship between serum levels of calcium, phosphorus, magnesium, zinc, copper, selenium, and vitamin D with the severity of pulmonary involvement in patients with CF. Methods: This cross-sectional study was performed on 84 patients with CF referred to Mofid Children’s Hospital, Tehran, Iran, in 2017. The collected data included demographic and anthropometric information. Laboratory evaluations included magnesium, copper, zinc, selenium, complete blood cell count (CBC), and vitamin D levels. The severity of pulmonary involvement was determined based on the Brasfield scoring system (BSS). Pearson correlation coefficient, t test, χ2 test, or Fisher exact test was used for analyses. Results: The mean age of the children was 6.8 ± 3.5 years, and 36 patients (43%) were female. Based on the z score, 53 patients (63%) were malnourished. The severity of pulmonary involvement was mild in 25 patients (30%), moderate in 39 patients (46%), and severe in 20 patients (24%). The percentages of deficiency related to vitamin D, zinc, copper, and selenium were 56%, 38%, 32.1%, and 21.4%, respectively. Among trace elements, there was a statistically significant relationship between the severity of pulmonary involvement according to BSS and serum copper (P = 0.007 and r = -0.229) and selenium deficiency (P &lt; 0.001 and r = -0.418). There was a significant relationship between malnutrition and vitamin D deficiency in patients (P = 0.034, r = 0.231). Conclusions: Serum copper concentration might affect respiratory function in CF patients. Selenium supplements should be added to patients’ diets. However, further interventional studies are required to investigate the possible causal relationships.

Impact of Menopause and the Menstrual Cycle on Oxidative Stress in Japanese Women.

Although estrogen possesses both pro- and anti-oxidant properties, its overall role in oxidative stress among women remains unclear, particularly since the influence of exogenously administered estrogen during previous studies differed by dose, administration route, and estrogen type. The aim of this study was to elucidate the effects of endogenous estrogen on oxidative stress in women. Thus, we performed a non-interventional observational study of healthy postmenopausal (n = 71) and premenopausal (n = 72) female volunteers. Serum levels of derivatives of reactive oxygen metabolites (d-ROMs, which are collectively a marker of oxidative stress), as well as the biological antioxidant potential (BAP, an indicator of antioxidant capacity), were compared between (1) pre- versus post-menopausal women, and (2) premenopausal women in early follicular versus mid-luteal phases of their menstrual cycles. We found that serum d-ROMs and BAP values in postmenopausal women were significantly higher than those in premenopausal women. Moreover, the d-ROM levels were significantly correlated with serum copper concentrations. However, neither d-ROMs nor BAP values were significantly affected by the menstrual cycle phase, although changes in d-ROMs between the follicular and luteal phases were significantly correlated with copper concentration shifts. These data indicate that postmenopausal hypoestrogenism is associated with elevated oxidative stress, although regular fluctuations of estrogen levels during the menstrual cycle do not influence oxidative stress.

Cuproptosis is involved in copper-induced hepatotoxicity in chickens

Copper (Cu) is an essential trace element, but it is also a ubiquitous environmental pollutant that threatens public health. Cuproptosis is a recently discovered cell death mode that unlike other programmed cell death, characterized by proteotoxic stress due to lipoylated protein aggregation and iron-sulfur cluster protein loss. Chickens as a high-trophic-level non-mammalian vertebrate that easily absorb and accumulate copper from the environment and food, but it is unclear whether the underlying molecular mechanisms that cause their hepatotoxicity under natural copper stress are related to cuproptosis. Therefore, we established animal models of chickens with different concentrations of copper exposure to dissect the role and mechanism of cuproptosis in chicken hepatotoxicity under natural copper stress. Our histopathological and biochemical results demonstrated that the liver structure with copper-treated exhibited dose-dependent damage. Meanwhile, copper treatment also dramatically increased serum and liver copper content and activated the expression of the membrane-associated copper transporter ATP7B. Furthermore, we found that Cu-exposure significantly increased the MDA content, and reduced the levels of T-AOC and SOD in serum and liver. Additionally, we found that the mRNA and protein levels of FDX1 were significantly upregulated in the 220 and 330 mg/kg Cu-treated groups. In our further studies, we found that copper did not alter protein levels of DLAT and DLST in chicken liver, but significantly increased Lipoylated-DLAT levels and oligomerization of Lipoylated-DLAT in the 330 mg/kg Cu-treatment group. Overall, we identified that FDX1-mediated protein lipoylation and proteotoxic stress indeed participate in copper-induced hepatotoxicity in chickens. Our results present novel insight into the pathogenesis of copper-induced hepatotoxicity in chickens and provide data to support filling in the role of cuproptosis in birds.

The Antitumor Impact of Combining Hepatic Artery Ligation With Copper Chelators for Liver Cancer.

Hepatocellular carcinoma (HCC) is one of the main cancer-related mortality worldwide. Thus, there is a constant search for improvement in treatment strategies to enhance the prognosis of this malignancy. The study aims to investigate the combined antitumor activity of ammonium tetrathiomolybdate (TM, copper chelator) combined with hepatic artery ligation (HAL) for liver cancer. A total of 40 Sprague-Dawley (SD) rats bearing hepatic tumors were randomly divided into four groups: the control group without any treatment (control), HAL only (HAL), given TM by gavage (TM), and given TM combined with HAL (HAL + TM). The concentrations of serum copper were measured at the predetermined time points. Tumor growth rate, overall survival (OS), expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and microvessel density (MVD), as determined by immunohistochemical examination, were compared. HAL treatment transiently could elevate alanine transaminase (ALT) and aspartate transaminase (AST) but resumed to baseline within 1 week. Serum copper was significantly increased in tumor-bearing animals over time. The values of serum copper in the three treatment groups were significantly lower than those in the control group at different time points, with the lowest values observed in the TM group (P < .05). The average tumor size was 30.33 ± 2.58, 20.83 ± 2.93, 16.80 ± 3.84, and 10.88 ± 1.08 mm in the control, HAL, TM, and HAL + TM groups, respectively (HAL + TM vs other groups, all P < .05). In addition, the expression levels of HIF-1α, VEGF, and MVD were significantly lower in the HAL + TM group than those in the other groups (P < .05). The OS of rats in the combined groups was significantly prolonged combined to the other groups (P < .05), with survival time of 19.1 ± 0.64, 25.4 ± 1.24, 25.3 ± 1.78, and 29.9 ± 2.22 days in the control, HAL, TM, and HAL + TM groups, respectively. These findings suggest that combined treatment with TM and HAL holds great potential for liver cancer treatment by reducing tumor hypoxia and angiogenesis. The observed results indicate that these combinations may offer a novel target and strategy for interventional therapy of liver cancer.

Evaluation of serum mineral status in dermatological disorders of dogs

The study was undertaken to evaluate serum mineral status, specifically zinc, copper and selenium in dogs affected with dermatological disorders in comparison to normal healthy dogs. The study included 40 dogs of 2-5 years of age with skin diseases presented to University Veterinary Hospitals at Mannuthy and Kokkalai under the Kerala Veterinary and Animal Sciences University, and ten apparently healthy dogs brought to the hospital for routine health check-up which served as control. Serum concentrations of the three minerals were compared not only between normal and dogs with skin diseases as a whole but also between individual skin diseases- six different skin diseases- with the control group. On comparing the dogs with skin ailments (n=40) and control group, the serum mineral levels analysed through Atomic Absorption Spectrophotometry (AAS) revealed that the concentration of zinc was significantly lower (p&lt;0.01) in the diseased group (0.53 ± 0.04 mg/L) of dogs (n=40) than the control group (1.11 ± 0.09 mg/L) and the serum copper concentration was also significantly reduced (p&lt;0.05) in diseased dogs (0.91 ± 0.08 mg/L) with respect to the control animals (1.23 ± 0.11 mg/L). The serum selenium concentration of diseased group of animals(n=40), however failed to show any significant difference from the control group of animals. The outcome of the study suggests a need for supplementation of zinc and copper in dogs with skin ailments like canine demodicosis that relapse even after prolonged therapy with acaricides.

Wilson’s Disease with Late Hepatic Involvement

Wilson’s Disease (WD) is an autosomal recessive condition that affects copper metabolism and manifests itself clinically in different ways. The diagnosis is indicated by low serum copper and ceruloplasmin concentrations, increased urine copper excretion and/ or increased hepatic copper concentrations. The present case report is about a 55-year-old male with chief complaints of loss of appetite, abdominal swelling, tremors in hand and head, slurring of speech for 10 days. Ultrasound (USG) findings were suggestive of liver cirrhosis with portal hypertension and liver function tests were also deranged. He was prescribed diuretics and asked to review after 10 days. Kayser-Fleischer ring was observed through slit lamp examination in both the eyes, which is a hallmark of WD. The Magnetic Resonance Imaging (MRI) of brain also revealed positive findings-hyperintensity throughout the mesencephalon for WD. Thereafter, the patient was treated with penicillamine and his symptoms improved after few days

Serum Mineral Levels and Haematobiochemical Parameters in Buffalo Calves with Allotriophagy (Pica Syndrome)

Pica is defined as a depraved or abnormal appetite characterized by licking and eating non-nutritive substances. The aim of this study was to report changes in the serum mineral levels and haematobiochemical parameters of buffalo calves with pica. The study included 30 buffalo calves exhibiting pica behaviour, such as licking stall walls or eating wool and non-food items (pica group), and 6 buffalo calves without the signs of pica behaviour (control group). The age of both groups ranged between 1 and 6 months. In the pica group, the haematological analysis revealed a decrease in red blood cells (P &lt; 0.001) and red cell distribution width (P &lt; 0.05) as well as an increase in the mean corpuscular volume and mean corpuscular haemoglobin (P &lt; 0.001), whereas the biochemical parameters were characterized by an increase in aspartate aminotransferase (P &lt; 0.01), alanine aminotransferase (P &lt; 0.001) and lactate dehydrogenase (P &lt; 0.05) levels and a decrease in creatinine and glucose (P &lt; 0.01) levels. Furthermore, the pica group showed a significant decrease in serum manganese, iron, zinc, selenium (P &lt; 0.001) and copper (P &lt; 0.01) concentrations. In conclusion, it was determined that deficiencies in the levels of serum iron, copper, zinc, manganese and selenium play an important role in the aetiology of pica in buffalo calves.

Update on copper and selenium in Canadian cow-calf herds: regional differences and estimation of serum reference values.

Trace mineral supplementation of beef cattle is essential for efficient reproduction and herd health. Understanding regional differences in cow trace mineral status could inform decisions about risks of deficiencies and supplementation management. Cow-calf surveillance projects provided three opportunities to evaluate the trace mineral status of Canadian beef cow herds. Blood samples were collected at pregnancy testing in 2014 from 102 cow-calf herds and in 2016 from 86 cow-calf herds in Western Canada. In 2019, blood samples were collected at pregnancy testing from cows in 163 cow-calf herds from Eastern and Western Canada. Serum samples were analyzed for copper, selenium, and molybdenum concentrations using a plasma mass spectrometer. The prevalence of copper deficient cows sampled from the Western provinces ranged from 24% to 43% across the three periods, and was 20% from Eastern Canada in 2019. The prevalence of selenium deficient cows ranged from 0.2% to 0.4% across the three projects in Western Canada, but was higher in Eastern Canada at 4.6% in 2019. High serum molybdenum was identified in 9.4% to 14% of cows across the three periods in Western Canada and in 15% of cows sampled in Eastern Canada in 2019. Serum copper, selenium, and molybdenum concentrations varied by cow age and month of sample collection. Serum selenium and molybdenum concentrations, but not copper, varied by soil type associated with the location of the farm. A subsample of samples from cows from Western Canadian herds provided body condition score (BCS) data, pregnancy status, and calf survival data and were used to estimate updated serum reference values for adequate concentrations. Age-specific values were required for selenium and molybdenum. Reference intervals (80%) were estimated from 2,406 pregnant beef cows from 99 herds with each cow having a BCS ≥ 2.5/5 and a live calf at 3 wk with no retained placenta: copper for all cows (0.379 to 0.717 ppm), selenium for cows <4 yr (0.052 to 0.152 ppm), and selenium for cows ≥4 yr (0.064 to 0.184 ppm). Upper 90% reference limits were also estimated for serum molybdenum for cows <4 yr (>0.104 ppm) and cows ≥4 yr (>0.110 ppm). The lower limits for the reference intervals for adequate copper and selenium are below those previously reported; nevertheless, they represent a large sample that was specifically applicable to extensively managed beef animals in western Canada.

Serum copper, zinc and selenium levels in women with unexplained infertility in Ibadan Nigeria: A cross-sectional analytical study.

Infertility is a global public health issue affecting couples. Trace metals have been implicated in effective reproductive functions in males but less studied in females. To compare the serum levels of copper (Cu), zinc (Zn), selenium (Se) and copper/zinc ratio in women with unexplained infertility and fertile women. This was a cross-sectional analytical study that compared 75 consenting women who had unexplained infertility with 74 fertile women that were controls. Both groups were seen within 1 year of delivery and were recruited from the family planning unit, at the University College Hospital, Ibadan. Data were obtained through a semi-structured questionnaire, after which 10 mL of venous blood was collected. Analysis of selected trace elements were done by atomic absorption spectrophotometry. IBM SPSS version 23 was utilized for data analysis and the levels of statistical significance was set at <0.05. The mean (± SD) serum concentrations of Cu (93.11 ± 16.55 μg/dL), Zn (72.04 ± 15.03 μg/dL) and Se (28.28 ± 8.33 μg/dL) amongst the women with unexplained infertility were lower when compared to the control group (all with P < 0.001). The serum Cu/Zn ratio was higher among the fertile women, though not statistically significant (P < 0.62). Age of <35 years was associated with normal serum levels of Cu (P < 0.01), while women with normal body mass index had low serum concentrations of Cu (P = 0.04), amongst the fertile group. Serum copper, zinc and selenium concentrations are significantly lower in women with unexplained infertility, therefore diets or supplements containing these trace elements may be helpful in their management.

Studying the association between cigarette smoking and serum copper, zinc, and magnesium concentrations: A cross-sectional study

Background and Objectives: Tobacco smoking causes damages almost for every organ in the body. Based on the literature review, the relationship between smoking, including nicotine dependence, and the serum zinc (Zn), copper (Cu), magnesium (Mg) status has not been studied sufficiently. The aim of the present study was to determine the relationship of cigarette smoking, including the nicotine dependence state of the smokers, with serum Cu, Zn, and Mg concentrations. Subjects and Methods: Overall, 41 active smokers and 44 nonsmokers were investigated for serum Cu, Zn, and Mg concentrations; in addition to urinary cotinine/creatinine ratio. The eight-item Fagerstrom test for nicotine dependence (FTND) questionnaire has been used to determine the nicotine dependence status of the smokers. Results: A significant hypozincemia has been detected in 34.1% of the smokers versus 9.1% of nonsmokers, with a five-fold higher risk than nonsmokers. Moreover, a significant hypomagnesemia has been detected in 24.4% of the smokers, with 6.7 fold higher risk than the nonsmokers. The serum Cu concentrations of the smokers were significantly higher (102.4 ± 17.5 μg/dl) than the nonsmokers (70.7 ± 17.1 μg/dl), (P < 0.0001). Each 1 year decrease in the initial age of starting smoking was associated with an increase in the serum Cu concentration by 0.016 μg/dl. Each increase in the serum Cu concentration by 1 μg/dl was associated with a decrease in the serum Zn and Mg concentrations by 0.4 μg/dl and 4 μg/dl, respectively. Conclusion: Cigarette smoking is a significant risk factor for hypozincemia, hypomagnesemia, and high Cu concentrations regardless of the nicotine dependence status of the smokers. Early management of hypozincemia may be a preventive measure to decrease the incidence of the oxidative stress-induced diseases.

Association of Serum Antioxidant Minerals and Type 2 Diabetes Mellitus in Chinese Urban Residents.

Antioxidant minerals including zinc, copper and selenium play critical roles in the maintenance of the redox balance in the body. However, their influences on type 2 diabetes mellitus (T2DM) are still inconclusive in Chinese populations. To elucidate the relationship between antioxidant minerals and T2DM, serum zinc, copper and selenium concentrations were measured in 1443 Chinese urban residents using a 1:2 matched case-control study. Conditional logistic regression models (CLR) were used to obtain the odds ratios (ORs) and 95% confidence intervals (CIs), and restricted cubic splines (RCS) were used to examine their dose-response associations. Serum zinc (OR = 0.52 [0.35, 0.77]) and copper concentrations (OR = 0.25 [0.17, 0.37]) were negatively associated with T2DM in a fully adjusted model. An L-shaped zinc-T2DM association (Poverall association = 0.003, and Pnonlinearity = 0.005) and a negative linear copper-T2DM association (Poverall association &lt; 0.0001, and Pnonlinearity = 0.395) were observed. No association was found between serum selenium and T2DM in fully adjusted CLR or RCS models. In addition, joint associations with T2DM were identified between serum zinc and copper and between serum selenium and copper. In conclusion, our study emphasizes the importance of an adequate intake of antioxidant minerals for T2DM prevention in the Chinese population.

Fatal congenital copper transport defect caused by a homozygous likely pathogenic variant of SLC31A1.

Known hereditary human diseases featuring impaired copper trafficking across cellular membranes involve ATP7A (Menkes disease, occipital horn disease, X-linked spinal muscular atrophy type 3) and ATP7B (Wilson disease). Herein, we report a newborn infant of consanguineous parents with a homozygous pathogenic variant in a highly conserved sequence of SLC31A1, coding for the copper influx transporter 1, CTR1. This missense variant, c.236T > C, was detected by whole exome sequencing. The infant was born with pulmonary hypoplasia and suffered from severe respiratory distress immediately after birth, necessitating aggressive mechanical ventilation. At 2 weeks of age, multifocal brain hemorrhages were diagnosed by cerebral ultrasound and magnetic resonance imaging, together with increased tortuosity of cerebral arteries. Ensuing seizures were only partly controlled by antiepileptic drugs, and the infant became progressively comatose. Laboratory investigations revealed very low serum concentrations of copper and ceruloplasmin. No hair shaft abnormalities were detected by dermatoscopy or light microscopic analyses of embedded hair shafts obtained at 4 weeks of life. The infant died after redirection of care and elective cessation of invasive mechanical ventilation at 1 month of age. This case adds SLC31A1 to the genes implicated in severe hereditary disorders of copper transport in humans.

Potential Role of Copper in Diabetes and Diabetic Kidney Disease.

Copper is a fundamental element for the homeostasis of the body. It is the third most abundant essential transition metal in humans. Changes in the concentration of copper in the blood are responsible for numerous diseases affecting various organs, including the heart, brain, kidneys, and liver. Even small copper deficiencies can lead to the development and progression of several pathologies. On the other hand, excessive exposure to copper can cause toxicity in many human organs, leading to various systemic alterations. In the kidney, increased copper concentration in the blood can cause deposition of this element in the kidneys, leading to nephrotoxicity. One of the most interesting aspects of copper balance is its influence on diabetes and the progression of its complications, such as Diabetic Kidney Disease (DKD). Several studies have shown a close relationship between copper serum levels and altered glycemic control. An imbalance of copper can lead to the progression of diabetes-related complications and impaired antioxidant homeostasis. A high Zinc/Copper (Zn/Cu) ratio is associated with improved renal function and reduced risk of poor glycemic control in patients with type two diabetes mellitus (T2DM). Furthermore, the progression of DKD appears to be related to the extent of urinary copper excretion, while regulation of adequate serum copper concentration appears to prevent and treat DKD. The aim of this review is to evaluate the possible role of copper in DKD patients.

The association between serum copper and obesity and all-cause mortality: the NHANES 2011-2016.

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 18years 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 133.9μg/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.

BMI Modifies the Association Between Depression Symptoms and Serum Copper Levels.

Depression is one of the most common mental disorders which dramatically threatens public health and wellness. Copper has been known to be involved in many biological processes that could help explaining the occurrence of depression. However, studies focusing on its effect have yielded mixed results. The present study aims to evaluate the association between serum copper levels and depression symptoms. It also investigates the effect of modification of BMI (body mass index) on depression symptoms. A total of 5419 US adults aged 20years or older from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 participated in the cross-sectional study. Logistic regression models were applied using depression levels as the outcome and serum cooper/selenium/zinc categories as the main predictor, with the adjustments of gender, age, marital status, race, education, family income level, alcohol drinking, cigarette smoking, diabetes, pressure, stroke, and BMI. The interaction terms for copper levels and other covariates were further incorporated into the model to assess their roles in predicting depression symptoms. The prevalence of depression symptoms was significantly higher in samples with a high copper level. Among the levels of serum copper, selenium, and zinc, only the association between depression symptoms and serum copper levels was observed to be significant in the unadjusted model (P = 0.002). Individuals with a high copper level (114-134μg/dL) and a very high copper level (≥ 134μg/dL) had 1.85 (95% CI 1.24, 2.77)- and 1.72 (95% CI 1.21, 2.44)-fold higher odds ratio of depression symptoms, respectively, compared to those with a normal serum copper level. Although the association was not significant in the adjusted models, in which confounders were added, the interaction of copper level, including high and very high copper levels, and obesity (BMI ≥ 30kg/m2) exhibited significantly higher odds ratio (4.12 (95% CI 1.38, 12.27) and 4.53 (95% CI 1.87, 10.96)) of having depression symptoms. The concentration of serum copper was positively associated with the prevalence of depression symptoms. Obesity exacerbated the risk of having depression symptoms in people with high serum copper levels.