Blood Copper Concentrations Research Articles

Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate

The effects of lead ingestion on parameters indicative of copper status, and particularly on the activity of the copper-dependent metalloenzyme superoxide dismutase (SOD) in erythrocytes, were investigated in weanling and neonatal rats. In a series of experiments, Sprague-Dawley or Long-Evans rats were fed a nutritionally adequate purified diet (AIN-'76). Lead acetate was given orally in the drinking water (0, 100, 250, or 500 ppm Pb) to groups of 23 to 26-day-old rats for 5 weeks or intragastrically (0, 5, 11, 22, or 45 mg Pb/kg body wt/day) to pups from postnatal Days 2 through 20. Lead ingestion (250 and 500 ppm Pb) by weanling rats resulted in decreased concentrations of copper in blood (erythrocytes and serum), liver, and spleen, in increased concentrations of iron in liver and spleen, in increased spleen weight, and in a small decrease in hemoglobin and hematocrit values. There was a significant decrease in the activities of the copper metalloproteins erythrocyte superoxide dismutase (SOD) and serum ceruloplasmin (Cp). In contrast, in the neonate we found no significant effects of lead on copper concentrations in blood or tissue or on other measures indicative of copper status. Despite high blood lead concentrations (1–3 μg/ml), SOD activity was not decreased in the neonatal rat. In addition, lead had no direct effect in vitro on the activity of bovine blood superoxide dismutase. On the basis of both the in vitro and in vivo studies, it appears likely that the observed decrease in SOD in young rats is caused indirectly by a lead-induced copper deficiency rather than by a direct inhibitory effect of lead.

Transport and distribution of copper injected into an albumin-deficient (analbuminemic) rat

1. Copper (Cu) concentrations in blood, liver, kidney, spleen and pancreas of an albumindeficient (Nagase analbuminemic) rat (NAR) were compared with those of a control (Sprague-Dawley) rat (SDR). 2. Cu concentrations were significantly higher in the blood and significantly lower in the liver of the NAR strain than those of the SDR strain in female control (saline-injected) groups at 8 weeks old. 3. Female NAR and SDR 8-week-old rats were injected i.p. with Cu at a single dose of 2.0 mg/kg body wt and killed 18hr later. Concentrations of Cu and other essential elements in the blood, liver, kidney, spleen and pancreas were determined simultaneously by inductively coupled plasma-atomic emission spectrometry. 4. Cu concentration in the liver was significantly lower in the NAR than in the SDR strain suggesting a role for albumin as a carrier protein of free Cu ions in the blood. 5. The effects of Cu loading on other essential elements (Zn, Fe, Ca, Mg, P) were also compared between the NAR and SDR strains.

Assessment of zinc and copper status of healthy elderly people using metabolic balance studies and measurement of leucocyte concentrations

Metabolic balance studies for zinc and copper were carried out in 24 apparently healthy elderly people aged 69.7 to 85.5 yrs, living in their own homes and eating self-selected diets. The zinc and copper concentrations in whole blood, plasma, and leucocytes were also measured. Mean daily intakes for zinc and copper were 137 and 20.1 µmol with mean retentions of 1.0 and −0.8 µmol, respectively. These values did not differ significantly from equilibrium (p < 0.01). For zinc and copper, respectively, mean concentrations were 11.0 and 19.4 µmol/1 in plasma, 120 and 11.5 µmol/106 cells in leucocytes, and 99 and 13.4 µmol/1 in whole blood. These data will provide normal standard values for elderly people in good health and should serve as a basis for the investigation of elderly people with suspected deficiencies of these trace metals.

Reduced cadmium body burden in cadmium-exposed calves fed supplemental zinc

The objectives of this study were to evaluate the use of practical supplemental dietary zinc to modify the cadmium content in edible bovine tissues and to identify copper interactions with cadmium and zinc. The effect of supplemental zinc (200 or 600 μg/g) on the concentrations of cadmium, zinc, and copper in liver, kidney cortex, muscle, and blood of calves fed 50 μg/g cadmium for 60 days was evaluated. Blood samples were collected before and eight times after starting to feed cadmium or cadmium plus zinc. Liver, kidney, and muscle samples were collected when calves were slaughtered (baseline, at beginning of experimental feeding; cadmium-fed, at end of 60 days feeding). The cadmium concentrations of all sample types collected were markedly increased by the feeding of cadmium. Feeding 600 μg/g supplemental zinc significantly increased the zinc concentrations of liver, kidney cortex, and blood and decreased the cadmium accumulation in these organs as well as muscle. The copper concentrations of muscle or blood were not altered by feeding cadmium with or without zinc but those of liver and kidney cortex were significantly increased by higher dietary levels of zinc and cadmium. The potential use of dietary zinc salts in reducing cadmium body burden in food animals suspected or known to have high cadmium intakes is suggested.

Absorption and excretion of organic compounds of copper by sheep

When sheep are injected subcutaneously with copper calcium edetate or copper oxyquinoline sulphonate there is a rapid increase in the concentration of copper in whole blood, serum and urine within the first 24 h. When sheep are injected with copper methionate the concentration of copper in whole blood and serum rises slowly over a period of about 10 days and there is no detectable increase in urinary copper. After the injection of each of the three compounds, there was a steady increase in the caeruloplasmin activity in serum over a period of 10 to 20 days, followed by a slow fall to pre-injection activity by 40 days. There was a marked increase in the β-globulin fraction of serum 9 days after the injection of copper methionate but not after the other 2 compounds and the amounts of 2 copper containing proteins in liver were greater 60 days after the injection of copper methionate than after the injection of the other two compounds. The copper content of the 3 organic compounds is absorbed and excreted at different rates by sheep. The amounts of copper-containing protein produced in the liver also differ according to the organic component of the compound injected. The results suggest that the lower toxicity of copper injected as methionate compared with that injected as copper calcium edetate or copper oxyquinoline sulphonate is due to the slower absorption and transport of the copper to the liver and kidney.

Zinc and copper concentrations in leucocytes and erythrocytes in healthy adults and the effect of oral contraceptives.

The content of zinc and copper of whole blood, plasma, erythrocytes and white cells, has been measured in normal controls. The concentrations of zinc and copper in leucocytes are about seven and ten times respectively higher than those in erythrocytes. Women taking oral contraceptives showed significant increases in the concentrations of copper in plasma and whole blood but not in leucocytes or erythrocytes. Oral contraceptives did not alter the concentration of zinc in any of the fractions or in whole blood. These data provide a baseline for the assessment of the body status of zinc and copper in various disease states in which deficiencies may be present.

Trace element concentrations and behavior: clinical utility in the assessment of developmental disabilities

Trace element and toxic metal concentrations were determined in blood and hair samples obtained from autistic, learning disabled, and control children between the ages of 6 and 12 years. The average hair and blood concentrations of copper, magnesium, zinc, and lead were within acceptable ranges. Serum copper and magnesium, plasma zinc, and whole blood lead concentrations were similar for all groups. Serum copper, plasma zinc, and whole blood lead were identified as predictors of group membership. The results of the present study provide support for inclusion of trace element profiles for diagnostic purposes with developmentally disabled children.

Variation in the activities of glutathione peroxidase and superoxide dismutase and in the concentration of copper in the blood in various breed crosses of sheep

Activities of the enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were examined in the blood of 364 ewes of a lowland grazing flock comprising Scottish Blackface ewes and crosses of that breed with Border Leicester, Cambridge, East Friesland, Oldenburg and Texel rams. Half were bled at 16 months old and again two years later, and half at 28 months old. Variation attributable to breed of sire was not statistically significant (P less than 0.1) for GSH-Px, but was significant for whole blood copper concentration (P less than 0.01) and for SOD activity (P less than 0.05) although the latter was complicated by a large breed by age interaction involving two of the breeds. The correlation of SOD activity (per g haemoglobin) and whole blood copper concentration was 0.5, and the intraclass correlation between the estimates of SOD activities two years apart was 0.7.

Copper oxide particles for grazing sheep

In a series of experiments aimed at evaluating copper oxide as a supplement, grazing sheep were dosed with varying quantities of copper oxide particles up to 64 g, and the toxicity, the rate of particle excretion, and copper storage in the liver and other tissues were recorded. The toxicities (LD50) of copper oxide particles were 1.17 and 1.80 g/kg liveweight for two groups of grazing adult fine-wool Merino sheep. Death usually occurred 88-96 days after the oral administration of the particles; mean hepatic copper concentrations of sheep dying from copper toxicity were 4122-4308 mg/kg DM. The rate of faecal copper excretion of copper-supplemented sheep, expressed as a percentage of the dose, was less when 50 g of particles were given than when the dose was 5 or 10 g, but excretion patterns were variable. The quantity of hepatic copper stored per g of copper oxide given declined as the dose increased from 0 to 32 g, but increased again at higher doses. Hepatic copper concentration reached a maximum 2-3 months after dosing and the rate of decline was positively related to dose rate; thus, large doses of copper are unlikely to extend the period of elevated copper status. Large doses also increased whole blood copper concentrations and elevated plasma aspartate transaminase activities; this was taken to indicate copper poisoning. Tissue copper concentrations from sheep given up to 64 g particles are reported; liver was the most sensitive to copper treatment. Copper contents of the lung and kidney also responded to copper therapy, but carcass components such as leg, shoulder and muscle did not. Weaned lambs given 2 g of particles (c. 0.13 g/kg liveweight) grew significantly faster than unsupplemented lambs. This dose rate was approximately one-seventh of that predicted to cause 5% mortality, and it is concluded that, at appropriate dose rates, this method of supplementation did not increase mortality or cause excessive increases in tissue copper concentrations, and could increase growth rate.

Copper complexes: a physiologic approach to the treatment of ‘inflammatory diseases’

Copper is an ‘essential’ metalloelement and as such it is required for life. Since none of the essential metalloelements can be synthesized in vivo it is required that they be obtained in the diet, If, following absorption, copper is not utilized immediately in the synthesis of copper-dependent enzymes it is either stored in the liver or excreted in a homeostatic fashion. It is well established that copper-dependent enzymes are required for cellular utilization of oxygen; dismutation of superoxide; cross-linking of collagen and elastin; synthesis of dihydroxyphenylalanine, melanin, norepinephrine, and epinephrine; metabolism of monoamines; and mobilization of stored iron for hematopoeisis. Other biochemical processes which are less well understood concerning the involvement of copper are: modulation of prostaglandin synthesis, lysosomal membrane permeability, modulation of histamine activity, angiogenesis, enhancement of synaptic vesicle attachment to neuronal plasma membranes, uptake and release of monoamines by synaptosomes, and activation of brain adenylate cyclase. A 2 to 3 fold increase in plasma or serum copper concentration is observed as a general response to infectious, inflammatory, and stress related diseases. It is well documented that blood copper concentrations increase in arthritic diseases, seizures, and neoplastic diseases and it is likely that there is a similar elevation with ulcers and diabetes. These elevations are viewed as a general acute phase physiologic response which facilitates remission. In the event that this physiologic response is impaired remission does not occur. Copper-containing components in blood are: ceruloplasmin which contains 6 atoms of copper and has a molecular weight of 132,000, a copper-albumin complex with a molecular weight of 69,000, and a variety of amino acid complexes with molecular weights in the range of 300 to 400. While there is always a highly significant correlation between the plasma copper increase and the increase in ceruloplasmin, further studies are needed to determine the relative change in concentration of each of the copper-containing components in the physiologic response to disease. This same increase in plasma copper concentration occurs in a variety of animal models of inflammation. Since treatment of these inflammations with exogenous low-molecular-weight copper complexes produces antiinfammatory effects the use of copper complexes may be viewed as a physiological approach to treatment. Low-molecular-weight copper complexes have been shown to have antiarthritic effects in man. In addition to being effective antiinflammatory agents copper complexes have been shown to be effective antiulcer, anticonvulsant, anticancer, and antidiabetic agents. This seeming diverse variety of pharmacologic effects are unified with the hypothesis that copper complexes facilitate or promote tissue repair processes involving copper-dependent enzymes and that arthritis, ulcers, seizures, neoplasia, and diabetes are diseases of specific tissues in disrepair. The corollary to this hypothesis is that the loss or reduction of copper-dependent enzyme mediated processes leads to tissue disfunction which may be re-established with copper complex therapy. Evidence will be presented to show that non-toxic doses of copper complexes have antiinflammatory activity in recognized models of inflammation and that copper complexes of antiinflammatory drugs are more effective than the parent drugs. Data will also be presented to show that copper complexes have antiulcer activity and that copper complexes of antiinflammatory drugs, which are well known ulcerogens, are also potent antiulcer agents. This observation supports the view that copper complexes of antiinflammatory drugs are less toxic than the parent drugs and suggests that complexation may have a role in ulcerogenesis. Anticonvulsant activity of copper complexes in two recognized models of seizure will be presented to show that complexes of non-anticonvulsant and convulsant ligands are effective anticonvulsant agents. In addition, data obtained with a copper complex of an antiepileptic drug suggests that the active form of these drugs may be their copper complexes. Recognition that neoplastic cells have reduced superoxide dismutase (SOD) activity and that copper complexes have SOD-like activity lead to the investigation of copper complexes as anticancer agents. Data will be presented to show that small molecular weight copper complexes inhibit solid Ehrlich tumor growth and increase survival. Following the observation that SOD inhibited streptozotocin-induced diabetes, small molecular weight copper complexes were studied and found to inhibit streptozotocin-induced diabetes as well. This observation will be presented in support of a possible role for copper complexes in the treatment of diabetes.

Injection of sheep with organic compounds of copper

Subcutaneous injections of up to 6 mg copper per kg body-weight as copper methionate (A) produced no deleterious effects in ewes. When copper was given in the form of copper calcium EDTA (B), deaths occurred within 48 hours of the subcutaneous injection of 3 or 4 mg copper per kg body-weight. There was centrilobular necrosis of the liver, necrosis of kidney tubules and excess fluid in the pleural and peritoneal cavities accompanied by the release of liver specific enzymes and a rise in the concentration of urea and creatinine in serum. The injection of 2 mg copper per kg body-weight produced a liver lesion at 48 hours with similar serum changes but recovery took place. Liver and kidney lesions occurred when the copper was in the form of diethylamine copper oxyquinoline sulphonate (C). In this case deaths occurred after the injection of 4, 3 or 2 mg copper per kg body-weight and liver damage followed by recovery was caused by 1 mg copper per kg body-weight. All compounds produced an increase in copper oxidase activity and in the concentration of copper in serum and whole blood. Compound A produced a slow increase in plasma copper concentration to a plateau between 5 and 10 days. Compounds B and C produced a rapid initial increase in the first few hours. The concentration fell rapidly for 12 or 24 hours and then more gradually. It is suggested that rapidity of absorption and transfer of copper to the liver and kidneys may be responsible for the toxic effects of compounds B and C.

Relationship of zinc and copper concentrations in maternal and cord blood and birth weight.

Twenty and 30 Nigerian women who delivered infants weighing 1500 gm-2500 gm and more than 2500 gm, respectively, were studied. Cord and maternal blood samples collected at delivery were analyzed by atomic absorption spectrophotometry for zinc and copper content. The mean plasma zinc in maternal and cord blood was significantly lower and the mean plasma copper was significantly higher in the low-birth-weight group than in the control group. The zinc level in cord blood was higher than that in maternal blood in both groups. However, the copper level in both groups was lower in cord than in maternal blood.

Zinc and copper concentrations in serum, blood and liver in moderate experimental pancreatic insufficiency.

Serum and liver concentrations of zinc and copper were studied in the rat after ligation of the pancreatic duct. Ligation of the bile duct was done close to the duodenum and high up in the hilum of the liver. The bile flow was by-passed into the intestine via a plastic catheter. The surgical method used was found suitable for a study of moderate exocrine pancreatic insufficiency since significant--although markedly reduced--concentrations of amylase and trypsin were estimated in intestinal contents at sacrifice 19 weeks after the operation. The serum zinc level was unaffected by duct ligation except for a slight decrease after 2 weeks. Similarly zinc in whole blood was unaffected. The copper concentration in serum was, however, significantly enhanced during in first 10 weeks. The copper zinc ration was markedly increased in duct ligated rats during the whole period. Zinc and copper concentrations in liver tissue were significantly decreased after 19 weeks. The findings suggest that a decrease function of exocrine pancreas might induce a disturbed balance of zinc and copper in the rat.

Effect of pulmonary tuberculosis on blood concentrations of copper and zinc.

An investigation of copper and zinc concentrations in active cases of pulmonary tuberculosis (TB) was undertaken. Whole-blood, plasma, and erythrocyte concentrations of copper and zinc were determined for TB patients and controls using atomic absorption spectrophotometry. Elevated whole-blood and plasma copper concentrations or depressed whole-blood and plasma zinc concentrations, or both, were characteristic of the TB patients. In most cases, however, the high copper concentrations and low zinc concentrations did not occur concurrently. The whole-blood and plasma copper/zinc concentration ratios were also significantly elevated in the TB patients.

Copper metabolism in the steely-hair syndrome.

STEELY-hair syndrome, described by Menkes et al. in 1962,1 is characterized by pili torti, developmental regression, seizures, temperature instability, arterial intimal abnormalities, and scorbutic bone changes.2 Danks et al. have suggested that these manifestations are due to systemic copper deficiency and have demonstrated severely diminished copper concentrations in blood, brain, and liver of patients with the syndrome.3 The copper deficiency appears to result from an impaired intestinal absorption of copper which is probably related to a defective transport of the ion across the serosal cell membrane. In an attempt to clarify the nature of the absorption defect, we performed copper . . .

Relationships between haemoglobin type and copper concentrations in whole blood and its components in sheep of different breeds

SUMMARYCopper concentrations were determined in whole blood, plasma and caeruloplasmin and calculated for red cells and non-caeruloplasmin copper in plasma in 215 female sheep, 9 months old, belonging to the Scottish Blackface, Cheviot and Welsh Mountain breeds of sheep and their crosses. Copper determinations were also made on red cells and plasma, and calculated for whole blood, of a contemporary group of 107 female sheep of the same breeds at the age of 4 years. Further, plasma copper concentrations were determined for these 107 sheep from samples taken on several occasions some years earlier.Within breed, sheep of type Hb B had significantly higher levels of copper than sheep of type Hb A in whole blood and most of the blood components. The biggest differences were found in plasma and were 19 ng/100 ml for one group and 37 Jig/100 ml for the other. Type Hb AB sheep were intermediate in copper level. The differences in plasma copper level associated with Hb type were present and of similar magnitude at different ages, seasons and average flock levels of copper.After adjustment for the effects of Hb type, breed differences in copper levels were significant for whole blood and all components but much less pronounced for red cells than for plasma. Copper levels in plasma and red cells were only moderately correlated (r = 0·23–0·40).Combined evidence suggests the existence of a gene with a marked effect on copper level which is linked to the locus for Hb type.

The seasonal cycle of copper concentration in Busycon canaliculatum L.

Individual tissues of approximately 100 whelks were analyzed for copper content. Tissue copper concentrations showed a high degree of individual variation, but seasonal trends were evident. In the digestive gland, the organ with the highest copper concentration, the mean monthly concentrations were about 5 to 10 times higher in the summer (400-900 µg Cu/g fresh weight) than in the winter (65-120 µg Cu/g). Gut concentrations followed the same seasonal trend. The copper concentration in the gonad increased in the early spring and then decreased in the late spring and summer to low fall and winter values. The total copper in the gonad increased 6-fold during the spring and summer, however, because of large increases in size as late summer spawning approached. The total copper in the gonad dropped off after the spawning season. Monthly average blood copper and protein concentrations followed the same seasonal pattern as the digestive gland and gut, with copper ranging from a monthly average of 42 µg/ml in February to 175 µg/ml in June. Nearly all the blood protein present was hemocyanin, and there was no apparent seasonal change in the ratio of copper: protein. The copper concentration of the kidney was similar to that of the blood during most of the year, but in late summer and fall it increased to a maximum (171 µg/g in Oct.), while that of the blood and other tissues was decreasing. Whelks in Narragansett Bay usually begin to feed in late May or early June; the general early summer increases in the copper concentration of most tissues correlated with this commencement of feeding.

The Concentration of Copper in Whole Blood, Plasma and Erythrocytes of Hereford Cattle during Pregnancy

The copper concentration in whole blood, plasma and erythrocytes of Hereford COWS prior to conception and at monthly intervals during gestation was measured. Between the third and fifth month of pregnancy there was a small but significant rise (P < 0.05) in plasma copper and a fall in erythrocyte copper. The erythrocyte copper concentration increased in the third trimester and the packed cell volume decreased significantly (P < 0.05) during the same period.

An association between the concentration of copper in whole blood and haemoglobin type in sheep

SUMMARYIn a genetically diverse flock of about 320 sheep a significant association has been found between the concentration of copper in whole blood and the haemoglobin type.Sheep were bled on four occasions over a period of 1 year, with the flock mean concentration of copper varying between 53 and 96 fig per 100 ml whole blood. The copper concentrations in whole blood from sheep of haemoglobin type B exceeded those from sheep of type A by 9, 16, 15 and 15 fig per 100 ml on the four occasions respectively. The copper concentrations from sheep of type AB were 8, 11, 7 and 7 μg higher than those from type A.Differences in the frequency of the three haemoglobin phenotypes accounted for part of the breed variation in copper concentration previously observed in the same flock, but even when that effect was allowed for, highly significant breed variation remained. When plasma instead of whole blood was examined in two other flocks from which breed variation in plasma copper concentration had been reported no association was found between the plasma copper concentration and haemoglobin type.

Acute copper intoxication. A hazard of hemodialysis

Clinical and laboratory finding from three patients with hemodialysis-induced copper intoxication included pancreatitis and myoglobinemia in addition to previously observed feature of this syndrome (gastrointestinal symptoms, leukocytosis, metabolic acidosis, and hemolysis). Copper concentration was measured in samples of serum, erythrocytes, whole blood, and dialysate. In all instances there was a significant hypercupremia following the inciting dialysis. A demonstrated erythrocyte to serum copper concentration gradient documents the ability of the erythrocyte to concentrate copper. It is important to measure the copper concentration in whole blood or erythrocytes in suspected instances of copper intoxication. The possible mechanisms of copper entry into the dialysate include oxidation of metallic copper to cupric ion or contamination of tap water from copper pipes. Copper ion significantly alters erythrocyte metabolism.