Effects of Different Copper Sources and Levels on Plasma Superoxide Dismutase, Lipid Peroxidation, and Copper Status of Lambs

This study was performed to determine the effects of different copper (Cu) sources and levels on plasma superoxide dismutase (SOD), lipid peroxidation, and Cu status of lambs. Fifty Dorper × Mongolia wether lambs (approximately 3?month of age; average BW?=?23.8?±?0.6?kg) were divided into five equal groups each with ten animals according to their weight. Treatments consisted of (1) control (no supplemental Cu), (2) 10?mg Cu/kg DM from Cu-lysine, (3) 20?mg Cu/kg DM from Cu-lysine, (4) 10?mg Cu/kg DM from tribasic copper chloride (Cu(2)(OH)(3)Cl; TBCC), and (5) 20?mg Cu/kg DM from TBCC. The Cu concentration was 6.74?mg/kg DM in the basal diet. Plasma copper concentrations and ceruloplasmin activities were not affected on day?30 by Cu supplementation. Copper supplementation increased plasma and liver copper concentrations and ceruloplasmin activities on day?60. Muscle Cu concentrations were not affected by Cu supplementation. There were no differences in plasma, liver, and muscle Cu concentrations and ceruloplasmin activities between Cu-lysine and TBCC. Liver copper concentrations and plasma ceruloplasmin activities were increased in lambs supplemented with 20?mg Cu/kg DM than in those supplemented with 10?mg Cu/kg DM on day?60. However, copper levels had no effects on Cu concentrations in plasma and muscle. Malondialdehyde (MDA) concentrations were decreased in plasma and liver tissues, but not affected in muscle by Cu supplementation. Plasma SOD activities were increased by Cu supplementation. There were no differences in plasma, liver, and muscle MDA concentrations and plasma SOD activities between Cu sources and levels. These results indicated that Cu supplementation increased plasma SOD activity, lipid oxidative stability, and copper status of lambs, but did not influence lipid oxidative stability in sheep muscle. Cu-lysine and TBCC were of similar availability when offered to finishing sheep.     

Hepatic Copper Accumulation in Primary Biliary Cirrhosis

Hepatic copper accumulation is a regular feature of primary biliary cirrhosis (PBC). The levels are directly related to the clinical stage of the disease. Since the copper values in PBC are comparable to Wilson''s disease, there is the potential for copper toxicity, although this is speculative since the two diseases differ in the binding, distribution, and intracellular localization of the copper. The involvement of copper toxicity in the progression of PBC is supported by the observation that the highest values occur in association with the hepatic failure that occurs in the advanced stage.Corticosteroid therapy appears to decrease hepatic copper levels in PBC. Although this therapy does not invariably lower the hepatic Cu content in patients with PBC, it does so in many individuals. Therapeutic trials with d-penicillamine are in progress. When results are available they will guide us in the management of individual patients with PBC. In the meantime, dietary copper should be restricted as is done in management of Wilson''s disease.     

Relationships Between Respiratory Function Disorders and Serum Copper Levels in Copper Mineworkers

The aim of this study was to investigate the respiratory function disorders that could be related to dust exposure during the production of copper mine in copper mineworkers (CMWs). The study included 75 male CMWs (mean age, 32.0 ± 7.1 years, 58.6% smokers) and 75 male age- and smoking status-matched healthy control subjects. Serum Cu level was significantly higher in the CMW group (0.80 ± 0.62 μg/ml) than the control group (0.60 ± 0.39 μg/ml) (p = 0.017). Significant negative correlations were found between serum Cu level and forced expiratory volume in first second (r = −0.600; p < 0.001) and between serum Cu level and forced vital capacity (r = −0.593; p = <0.001) in CMWs. Serum Cu level was significantly higher in the restrictive type pulmonary function disorders group (1.36 ± 0.62 μg/ml) than obstructive type (0.90 ± 0.55 μg/ml) and normal pulmonary function pattern group (0.53 ± 0.43 μg/ml) (p < 0.001). Patients with radiological parenchymal abnormalities had significantly higher serum copper levels than those without abnormalities (1.53 ± 0.52 vs. 0.71 ± 0.52 μg/ml, respectively; p = 0.002). In conclusion, result of the study has shown a negative association between pulmonary functions disorders and radiological abnormalities and serum Cu levels in CMWs.     

Hair Selenium Levels in Hepatic Steatosis Patients

The purpose of this study was to assess hair selenium levels of liver patients suffering from hepatic simple steatosis and non-alcoholic steatohepatitis (NASH) in central areas of China. Selenium was measured by an atomic absorption spectrophotometer equipped with the hydride generation system. The levels of selenium in healthy individuals ranged between 0.3 and 0.9 μg/g, and mean hair selenium levels in the male population and female population were 0.59?±?0.18 and 0.57?±?0.15 μg/g, respectively. These concentrations did not vary significantly (P?>?0.05) in relation to the gender. One hundred-eighteen individuals of both sexes aged between 15 and 60 years with hepatic simple steatosis and NASH were selected for this study. The mean and standard deviation of hair selenium concentrations observed in male and female patients with hepatic simple steatosis were 0.54?±?0.16 and 0.50?±?0.15 μg/g, respectively, while the mean and standard deviation of hair selenium concentrations observed in male and female patients with NASH were 0.40?±?0.14 and 0.41?±?0.12 μg/g. Analysis of t test showed a significant difference between NASH (P?<?0.001) patients in hair selenium concentrations when compared with controls.     

Serum Zinc and Copper Levels in Ischemic Cardiomyopathy

Changes in the copper (Cu) and zinc (Zn) concentrations have been reported previously in ischemic cardiomyopathy (ISCMP). Due to controversial results, the aims of this study were to compare levels of Cu, Zn, and Zn/Cu ratio of ISCMP patients with healthy volunteers and also to investigate the possible relationship between trace elements status in ISCMP patients with the severity of clinical disease based on the New York Heart Association (NYHA) classification. The subjects of this study consisted of 30 ISCMP and 27 healthy volunteers. ISCMP was diagnosed with a history of previous myocardial infarction and also coronary artery disease was confirmed by coronary angiography. Exclusion criteria were renal or hepatic insufficiency, alcohol usage, and intake of supplements containing Cu or Zn within 1 week. Cu and Zn levels have been assayed with atomic absorption spectrophotometry. Statistical analysis was performed with the SPSS 10 software using independent sample t test for comparing the levels of Cu and Zn between ISCMP and normal subjects. The mean Cu level of the ISCMP group (1.54 ± 0.52 mg/L) was significantly more than the Cu levels of the healthy volunteers (1.31 ± 0.24 mg/L; p = 0.048). The mean Zn levels of the ISCMP and healthy volunteers were 1.05 ± 0.28 and 1.12 ± 0.42, respectively, without any significant difference between groups. There was a trend for higher Cu level, lower Zn level, and lower Zn/Cu ratio in NYHA III patients in comparison with NYHA II group. Considering the results of this study, Cu may have a role in the development of ISCMP. Interventions such as administration of Cu chelators to relieve the symptoms or to decrease the progression of ISCMP is needed to be examined in large clinical trials. In this study, the Zn level of ISCMP patients was not significantly different in comparison with the healthy volunteers.     

Selenium and Glutathione Peroxidase Levels in Lambs Receiving Feed Supplemented with Sodium Selenite or Selenomethionine

Twenty-one 6 months old female lambs were divided into 7 groups and fed a basal diet containing 0.13 mg Se/kg. The basal diet was further supplemented with 0, 0.1, 0.5 or 1.0 mg Se/kg either as sodium selenite or as selenomethionine, and was fed for 10 weeks. Both feed additives produced an increase in the selenium concentration in the tissues analysed. Significant correlations were found between the concentrations of selenomethionine or sodium selenite added to the feed and the subsequent tissue levels. However, the selenium levels seemed to plateau at approximately 0.5 mg Se/kg of supplemented sodium selenite. The total glutathione peroxidase (GSH-Px) activity of the tissues increased when the selenium supplementation increased from 0 to 0.1 mg/kg for both selenium compounds. With further increase in selenium supplementation the GSH-Px activity in the tissues plateaued except in the blood where the activity continued to rise with increasing selenomethionine supplementation. The selenium dependent GSH-Px activity in the liver rose with increasing selenomethionine supplementation, but approached a plateau when 0.1 mg Se/kg as sodium selenite was added to the feed. The selenium concentration in whole blood responded more rapidly to the selenium supplementation than did GSH-Px activity. The experiment indicates that the optimal selenium concentration in the feed is considerably higher than 0.1 mg Se/kg, and that selenium levels of 1.0 mg/kg in the feed do not result in any risk for the animals or the consumers of the products.     

Serum Copper and Zinc Levels in Patients with Endometrial Cancer

Biological Trace Element Research - The aim of the present study was to evaluate serum concentrations of copper (Cu) and zinc (Zn), in relation with metabolic profile and clinicopathologic features...     

Interstitial Lung Disease in Coppersmiths in High Serum Copper Levels

Coppersmith is a worker who uses copper most commonly for the production of kitchen appliances in Turkey. This is an ancient occupation practiced for centuries in Turkey. Our objective was to investigate the prevalence of parenchymal lung diseases among coppersmiths in Kahramanmaras city in Turkey. Thirty coppersmiths were included to the study, and they all signed an informed consent. Demographics, spirometric test results and high-resolution computed tomography (HRCT) scans, and blood samples were obtained. Laboratory analysis of the serum samples showed that serum copper levels of the subjects were 0.93 ± 0.14 mg/L. Serum copper level in control group was found as 0.70 ± 0.14 mg/L, and it was significantly different between the two groups (p < 0.05). Of 30 coppersmiths, 17 HRCT findings are abnormal and seen with diffuse parenchymal interstitial lung disease pattern—ten (58.8%) respiratory bronchiolitis interstitial lung disease, five (29.4%) nonspecific interstitial pneumonia, and two (11.8%) usual interstitial pneumonia. The most prevalent HRCT pattern was micronodular pattern in workers. This is the first field study reporting the radiologic findings of coppersmiths and effect of the occupation on lung diseases.     

Serum Copper and Zinc Levels in Healthy Greek Children and Their Parents

The aim of this study was to investigate whether there is a correlation between copper (Cu) and zinc (Zn) levels in children and their parents, considering their nutritional habits. Cu and Zn concentrations were measured by flame atomic absorption spectrophotometry in the serum of 66 healthy children, aged 3–14 years, and their parents, residing in a region of Greece (Thrace). Cu levels were higher in mothers than those in fathers, but they were lower in both parents than those in children. They also tended to decrease with age in both parents and children, whereas Zn levels significantly increased with age in children. There was a positive correlation between children's and mothers' Zn levels, as well as children's and both parents' Cu levels. Children used to eat meat, fish, vegetables, and legumes as frequently as their parents, but they were consuming more eggs, milk, and fruits than the latest. Regarding parents' diet, higher Zn levels were depended on the consumption of meat and milk, whereas higher Cu levels were depended on the consumption of milk. Consequently, children’s Cu and Zn levels are related to their parents’ levels, which can be influenced by their nutritional habits.     

Source of Copper May Have Regressive Effects on Serum Cholesterol and Urea Nitrogen Among Male Fattening Lambs

An experiment was conducted to determine the effect of dietary copper (Cu) on mineral profile, hematological parameters, and lipid metabolism in lambs. Eighteen Zandi male lambs (approximately 3 months of age; 17.53?±?1.6 kg of body weight) were housed in individual pens and were assigned randomly to one of three treatments. Treatments consisted of (1) control (no supplemental Cu), (2) 10 mg Cu/kg dry matter (DM) from copper sulfate (CuS), and (3) 10 mg Cu/kg DM from Cu proteinate (CuP). The Cu concentration was 8.2 mg/kg DM in the basal diet. Blood was sampled from the jugular vein at the beginning of the study (enrollment, before feeding Cu supplement) and at days 25, 50, and 70 of experiment. The amounts of total serum glucose, urea nitrogen, calcium, phosphorus, iron, copper, zinc, and lipids and hematological parameters were measured. Average daily gain and feed efficiency were improved (P?<?0.05) with Cu supplementation and were better for the lambs fed diet supplemented with CuP. The concentrations of serum Ca, P, and Zn were not affected by source of Cu in the diet. However, Fe concentration was lower (P?<?0.01) in the Cu-supplemented groups. Experimental treatment had no significant effects on the hematological parameters. The serum glucose concentration was not affected by treatments. However, the urea nitrogen concentrations were significantly affected (P?<?0.05) by added Cu and was lower for CuP group as compared to the lambs in the CuS and control groups. Addition of Cu had no influence (P?>?0.05) on the serum triglyceride concentration, but lambs fed with CuP supplement had lower (P?<?0.05) serum cholesterol than the CuS and control animals. These results indicated that CuP supplemented at 10 mg/kg DM improved gain and enhanced the efficiency of nitrogen in male lambs.     

Characterization and Identification of Hepatic mRNA Related to Copper Metabolism and Homeostasis in Cattle

Copper is an essential trace mineral required for growth and development. Copper homeostasis within the cell is mediated by the expression of the Cu transporter protein (CTR1), ATPase7A (ATP7A), ATPase7B (ATP7B), Cox17, and Cu chaperone for Cu–Zn superoxide dismutase (CCS) which helps to regulate Cu uptake, export, and intracellular compartmentalization in non-ruminants. Copper also serves as a cofactor of antioxidant, superoxide dismutase1 (SOD1). Liver tissue from eighteen Holstein bull calves (average BW 201?±?58.5 kg, 7.3?±?1.9 months) from a previous experiment were utilized to characterize and identify hepatic mRNA related to Cu metabolism and homeostasis in cattle. Hepatic Cu concentration was determined via flame atomic absorption, and total RNA was extracted using TRI reagent and purified using RNeasy. Hepatic Cu concentrations ranged from 86 to 801 mg of Cu/kg DM. Real-time polymerase chain reaction analysis revealed that CTR1, ATP7A, and ATP7B mRNA expressions were negatively correlated with hepatic Cu concentration, while CCS (P?=?0.0887) and SOD1 had a tendency (P?=?0.0733) to be negatively correlated to hepatic Cu concentration. These data indicate that higher than normal hepatic Cu concentration downregulates gene expression of CTR1, ATP7A, ATP7B, and Cox17, which are involved in bovine liver copper homeostasis.     

Serum Concentration of Copper,Zinc, Iron,and Cobalt and the Copper/Zinc Ratio in Horses with Equine Herpesvirus-1

The serum concentrations of copper, zinc, iron, and cobalt and copper/zinc ratio were investigated in horses infected with equine herpesvirus-1 (EHV-1). Nine horses were naturally infected with the virus and nine healthy horses served as controls. The concentrations of copper, zinc, iron, and cobalt were determined spectrophotometrically in the blood serum of all horses. The results were (expressed in micrograms per deciliters) copper 2.80 ± 0.34 vs 1.12 ± 0.44, zinc 3.05 ± 0.18 vs 0.83 ± 0.06, iron 2.76 ± 0.17 vs 3.71 ± 0.69, cobalt 0.19 ± 0.37 vs 0.22 ± 0.45, and copper/zinc ratio 0.72 ± 0.38 vs 1.41 ± 0.36 for control vs infected group, respectively. In conclusion, copper and zinc concentrations of the infected group were lower than the control group (p < 0.001), whereas iron concentration and the copper/zinc ratio of the infected group were higher than the control group (p < 0.05 and p < 0.001). The cobalt concentration was not found to be statistically different between two groups. It might be emphasized that copper/zinc ratio was significantly affected by the EHV-1 infection, so it could be taken into consideration during the course of infection. An erratum to this article can be found at     

Zinc and Copper Levels in Bladder Cancer: A Systematic Review and Meta-Analysis

It is well documented that oxidative stress is involved in the pathogenesis of bladder cancer. Zinc (Zn) and copper (Cu) are important components of antioxidants. However, the association between Zn or Cu levels and bladder cancer remains elusive. The present study was designed to investigate the alteration of serum and urinary levels of Zn or Cu in bladder cancer patients compared with controls by performing a systematic review. We searched the PubMed, Embase, and Cochrane databases from January 1990 to March 2013 to identify studies that met our predefined criteria. Six studies were included. Bladder cancer patients demonstrated significantly lower levels of serum Zn (three studies, random effects standard mean deviation (SMD): ?1.072, 95 % CI: ?1.489 to ?0.656, P <0.0001), markedly higher levels of serum Cu (three studies, random effects SMD: 1.069, 95 % CI: 0.302 to 1.836, P?=?0.006) and urinary Zn (three studies, random effects SMD: 2.114, 95 % CI: 0.328 to 3.899, P?=?0.02) compared with controls. No obvious difference was observed in urinary Cu levels between bladder cancer patients and controls (two studies, random effects SMD: 0.153, 95 % CI: ?0.244 to 0.55, P?=?0.449). No evidence of publication bias was observed. In conclusion, the disorder of Zn and Cu is closely associated with bladder cancer. Frequent monitoring and early intervention should be recommended.     

Urinary Hepcidin Levels in Iron-Deficient and Iron-Supplemented Piglets Correlate with Hepcidin Hepatic mRNA and Serum Levels and with Body Iron Status

Among livestock, domestic pig (Sus scrofa) is a species, in which iron metabolism has been most intensively examined during last decade. The obvious reason for studying the regulation of iron homeostasis especially in young pigs is neonatal iron deficiency anemia commonly occurring in these animals. Moreover, supplementation of essentially all commercially reared piglets with iron entails a need for monitoring the efficacy of this routine practice followed in the swine industry for several decades. Since the discovery of hepcidin many studies confirmed its role as key regulator of iron metabolism and pointed out the assessment of its concentrations in biological fluids as diagnostic tool for iron-related disorder. Here we demonstrate that urine hepcidin-25 levels measured by a combination of weak cation exchange chromatography and time-of-flight mass spectrometry (WCX-TOF MS) are highly correlated with mRNA hepcidin expression in the liver and plasma hepcidin-25 concentrations in anemic and iron-supplemented 28-day old piglets. We also found a high correlation between urine hepcidin level and hepatic non-heme iron content. Our results show that similarly to previously described transgenic mouse models of iron disorders, young pigs constitute a convenient animal model to explore accuracy and relationship between indicators for assessing systemic iron status.     

Zinc and Copper Levels in Severe Heart Failure and the Effects of Atrial Fibrillation on the Zinc and Copper Status

Oxidative stress is involved in the pathogenesis of congestive heart failure (CHF). Some trace elements serve as antioxidant defenses. The purpose of this study was to analyze the effect of atrial fibrillation (AF) on zinc (Zn) and copper (Cu) levels in patients with advanced CHF. In this prospective study, serum Zn and Cu levels in 78 patients with clinically advanced CHF, i.e., New York Heart Association (NYHA) functional class III or IV (40 patients with AF and 38 in sinus rhythm) were measured using atomic absorption spectrophotometry. All patients also had a left ventricular ejection fraction (EF) of <35%. We recruited 40 volunteers with nearly the same age and weight as control. They had normal EF. There was no significant difference between patients with AF and those with sinus rhythm regarding serum Zn and Cu levels. However, both groups showed significant hypozincemia (p < 0.000) and a decreased Zn/Cu ratio (p < 0.03) compared with control group. Serum Cu levels were similar in the two groups and did not differ significantly from the control group. In patients with advanced CHF, irrespective of the rhythm, profound hypozincemia, and a decreased Zn/Cu ratio were present, which could be secondary to the activation of the renin–angiotensin–aldosterone system and CHF medications. The results suggest the need for more studies focusing on possible benefits with Zn nutriceutical replacement in patients with advanced CHF.     

The Relationship Between Plasma and Brain Quinolinic Acid Levels and the Severity of Hepatic Encephalopathy in Animal Models of Fulminant Hepatic Failure

Abstract: Quinolinic acid is an excitatory, neurotoxic tryptophan metabolite proposed to play a role in the pathogenesis of hepatic encephalopathy. This involvement was investigated in rat and rabbit models of fulminant hepatic failure at different stages of hepatic encephalopathy. Although plasma and brain tryptophan levels were significantly increased in all stages of hepatic encephalopathy, quinolinic acid levels increased three- to sevenfold only in the plasma, CSF, and brain regions of animals in stage IV hepatic encephalopathy. Plasma-CSF and plasma-brain quinolinic acid levels in rats and rabbits with fulminant hepatic failure were strongly correlated, with CSF and brain concentrations ∼10% those of plasma levels. Moreover, there was no significant regional difference in brain quinolinic acid concentrations in either model. Extrahepatic indoleamine-2,3-dioxygenase activity was not altered in rats in stage IV hepatic encephalopathy, but hepatic l -tryptophan-2,3-dioxygenase activity was increased. These results suggest that quinolinic acid synthesized in the liver enters the plasma and then accumulates in the CNS after crossing a permeabilized blood-brain barrier in the end stages of liver failure. Furthermore, the observation of low brain concentrations of quinolinic acid only in stage IV encephalopathy suggests that the contribution of quinolinic acid to the pathogenesis of hepatic encephalopathy in these animal models is minor.     

Serum Copper,Zinc, and Magnesium Levels in Patients with Chronic Fluorosis

Although there are many studies on effect of fluoride on trace elements in experimental animals, few studies exist on serum trace elements levels in patients with endemic fluorosis. We aimed to determine the serum levels of trace elements including serum copper (Cu), zinc (Zn), and serum levels of minerals including calcium (Ca), phosphorus (P), magnesium (Mg), sodium (Na), potassium (K) in patients with endemic fluorosis. The study group consisted of 30 patients with endemic fluorosis (17 females, 13 males, mean age 33.53 ± 9.85 years). An age, gender, and body mass index matched 30 healthy volunteers comprised control group (21 females, ten males with a mean age 33.93 ± 7.39 years). Urine fluoride levels of chronic fluorosis patients were significantly higher than that of control subjects as expected (1.92 ± 0.10 mg/l vs. 0.41 ± 0.09 mg/l, respectively; P < 0.001). Serum Cu levels (89.14 ± 16.77 μg/dL vs. 102.69 ± 25.04 μg/dL, respectively, P = 0.017), serum Zn levels (77.98 ± 20.58 μg/dL vs. 94.57 ± 35.87μg/dL, respectively, P = 0.032), and serum Mg levels (1.92 ± 0.18 mg/dL vs. 2.07 ± 0.31 mg/dL, respectively, p = 0.022) was significantly lower in chronic fluorosis patients than in controls. There were no statistically significant differences between the fluorosis group and control group with respect to serum levels of Na, K, Ca, and P. We concluded that chronic fluorosis is associated with reduced serum levels of Cu, Zn, and Mg.