COPPER ADMINISTRATION TO YOUNG CALVES: ORAL DOSING WITH COPPER OXIDE COMPARED WITH SUBCUTANEOUS COPPER GLYCINATE INJECTION

Calves were dosed with 50 g of copper oxide granules orally or given 120 mg copper glycinate subcutaneously. There was no significant difference between the weights of calves given either treatment during the trial. However, the copper oxide treatment resulted in sustained higher concentration of plasma copper and higher liver reserves than the glycinate treatment.     

Effect of staphylococcal contamination of the bovine udder on milk yield

Zinc sulphate was added to the drinking water of Angus cows and calves grazing an area considered marginal for copper nutrition of cattle. Mean daily intakes of approximately 12–15 mg Zn/kg live-weight further depressed already low plasma copper concentrations to levels considered to indicate copper deficiency. The plasma copper concentrations in untreated animals increased during the trial indicating adequate copper intakes during this period, but the high zinc intakes of treated animals prevented this seasonal rise. Injection of copper glycinate (0.24 g/animal) alleviated the depression of plasma copper associated with the high zinc intakes. The zinc supplements had little effect on plasma zinc concentrations.     

Rates of change in liver copper concentration in cattle given a copper-deficient diet,with or without pre-treatment with tetrathiomolybdate,for evaluation of two parenteral copper supplements

AIM: To minimise the impact of initial variation in liver copper (Cu) on assessments of Cu supplements for cattle in depletion/repletion experiments.

METHODS: Efficacy of two Cu injections was assessed with 18 calves, weighing 200–250 kg, given a Cu-deficient barley diet, containing 4.1 mg Cu/kg dry matter (DM) and added molybdenum (3 mg/kg) and sulphur (3 g/kg). Initial liver biopsy Cu ranged from 3.15–14.17 mmol/kg DM and nine calves with the highest values were given three subcutaneous injections of 235 mg tetrathiomolybdate (TTM) after 42–46 days depletion to lower liver Cu. Untreated (L) and TTM-treated (H) calves were ranked separately for liver Cu after 50 days depletion and allocated to one of three treatments: 100 mg Cu given subcutaneously as CuCaEDTA in either a paraffin (CuP) or aqueous base (CuA) after 56 days depletion (Day 0) or no injection (O). Thereafter, plasma and liver biopsy Cu were measured every 2–4 weeks for 16 weeks. Responses in liver Cu to Cu injections were compared with and without log_e transformation and by linear regression.

RESULTS: Prior to Cu injection, the fractional decline in liver Cu concentration (FDLCu) after 50 days depletion was 0.64 (SE 0.066) and 0.80 (SE 0.090) in H and L calves, respectively (p=0.09) and mean liver Cu did not differ on Day ?6 (6.65 (SE 0.516) and 4.91 (SE 0.681) mmol/kg DM, respectively). Mean plasma Cu was higher in H than L calves on Day 0 (16.6 (SE 0.52) and 13.3 (SE 0.49) μmol/L, respectively (p<0.001)). Rates of decline in log_e liver Cu between Days 0–84 in treatments L and H were: 0.0138 and 0.0071 for Groups O; 0.0033 and 0.0016 for Groups CuP; 0.0073 and 0.0049 for Groups CuA (pooled SE 0.0014) mmol/kg DM/day, respectively. Between Days 84–114, FDLCu was uniformly high across experiments and groups (0.59 (SE 0.042)). Cu injections did not affect plasma Cu, which remained 3.1 (SE 0.41) umol/L higher in Experiment H than in L (p=0.017).

CONCLUSIONS: The use of rates of change in liver copper concentrations improved the assessment of efficacy for two parental copper supplements and that of pre-treatment with tetrathiomolybdate, which, contrary to expectation, slowed Cu turnover by mechanisms that remain unclear.     

Predicting copper status in beef cattle using serum copper concentrations

Copper deficiency is common in pasture-fed cattle in New Zealand⁽¹⁾. In general, the diagnosis of copper deficiency in a herd of cattle is based on a combination of history, examination of animals, examination of the environment, chemical analysis of blood, liver or pasture, and treatment response trials. The laboratory diagnosis of copper deficiency is currently based on liver and either plasma or serum concentrations of copper. Ellison⁽²⁾ reviewed the copper reference range for cattle used by the animal health laboratories in New Zealand and concluded that there is strong agreement in the literature that serum copper concentrations greater than 7.9 𝛍mol/l and liver copper concentrations greater than 95 𝛍mol/kg are adequate for young cattle. Furthermore, it has been reported that if copper concentrations in the liver are greater than 150–200 𝛍mol/kg wet weight, there is a negligible increase in serum copper as liver concentrations increase further⁽²⁾, with individual animal variation accounting for the range of values in serum copper at this point (7.9–18 𝛍mol/l).     

Changes in liver copper concentration of thoroughbred foals from birth to 160 days of age and the effect of prenatal copper supplementation of their dams

OBJECTIVES: To monitor the change in liver copper concentration of Thoroughbred foals from birth to 160 days of age and to determine the effects of supplementation by two injections of copper edetate given to dams in late gestation on the liver copper concentration of their foals at birth. PROCEDURE: Ten mares pregnant to the same stallion were randomised into two groups on the basis of age, liver copper concentration and expected foaling date. The treatment group mares were given 100 mg and 250 mg copper edetate intramuscularly during the ninth and tenth months of gestation respectively. Foals had liver biopsies taken weekly in the first month of life, then monthly for four months. Foals were euthanased at 160 days of age; liver samples were taken and the copper concentrations were determined. RESULTS: Two distinct patterns of age dependent decline in liver copper concentration were evident. The mean (+/- SD) liver copper concentration of the foals was high at birth (374 +/- 130 mg/kg DM), and for seven it declined to adult values by 160 days of age (21 +/- 6 mg/kg DM). In three foals the decline was at a slower rate than in the other seven and at 160 days of age the mean concentration was 162 +/- 32 mg/kg DM. Repeated measures analysis showed significant differences between each biopsy (P < 0.01) and between 'normal' and 'accumulator' foals (P < 0.002). Copper injections given to mares in late pregnancy had no effect on the liver copper concentration of foals at birth. CONCLUSIONS: The significance of the two patterns of age dependant decline in liver copper concentration is unknown. Parenteral copper supplementation of the dam in late gestation had no effect on the liver copper concentration of the foal at birth.     

A study of the effects of copper deficiency in Scottish blackface lambs on improved hill pasture

One member of each pair of twin lambs from 37 five-and six-year-old Scottish blackface ewes, grazing reseeded pasture suspected of causing a molybdenum-sulphur induced copper deficiency in sheep, was given an injection of 12.5 mg copper calcium edetate at about eight weeks of age. Plasma copper concentrations of these lambs were maintained in the normal range by further injections of copper as required (treatment group). The remaining member of each twin pair received no copper therapy (control group). The control lambs and all ewes showed marked hypocupraemia throughout lactation, whereas the plasma copper concentrations of the treatment lambs, and also of single lambs with continuous access to unimproved hill grazings, remained normal. The live-weight gain of the treatment lambs was significantly greater than that of the control lambs, the difference in mean live-weights after 12 weeks being 2.5 kg. All lambs showed some degree of osteoporosis; this was most severe in the control lambs which had less dense bones and were also more susceptible to bone fractures and to disease. Differences between treatment and control lambs were also observed in haematological parameters and in fleece characteristics.     

Safety and effectiveness of cupric oxide particles for increasing liver copper stores in sheep

Five groups of four, housed Cheviot ewes (mean live-weight 50 kg) were given single doses of 0, 2.5, 5, 10 or 20 g cupric oxide particles in gelatin capsules while receiving a diet of marginal copper content based on pelleted oats. After 65 days liver copper concentrations had increased curvilinearly in relation to dose and all ewes given 10 or 20 g cupric oxide particles showed increases of at least 13.4 mmol kg-1 dry matter (850 ppm). Liver copper concentrations had generally declined after 85 days but biochemical and histological evidence of copper toxicity was recorded in one ewe which had received 20 g cupric oxide particles. Despite marked variations between individual sheep a dose of 0.1 g kg-1 liveweight (5 g) was considered to be safe and did not induce clinical copper toxicity in five sheep of the susceptible North Ronaldsay breed given the same basal diet.     

Trace element supplementation of sheep: evaluation of various copper supplements and a soluble glass bullet containing copper, cobalt and selenium

The effect of 5 different copper supplements on copper status of Merino sheep at pasture was examined. Transient increases in plasma copper concentrations occurred following treatment with copper calcium EDTA, copper sulphate, and glass bullets impregnated with copper, cobalt and selenium, but these increases were not considered to be a reliable indication of changes in liver copper reserves. Sheep receiving the glass bullet or 2.5 g oxidised copper wire particles orally or 50 mg copper as copper calcium EDTA parenterally had liver copper concentrations significantly greater than those of untreated sheep for periods up to 51 weeks. Oral doses of 30 mg copper as copper oxychloride, or 300 mg copper as copper sulphate did not alter the liver copper reserves at any stage. The bodyweight and greasy fleece weights were not significantly altered by any of the copper supplements. Plasma vitamin B12 concentrations in sheep given the glass bullet were increased for about 5 months. Thereafter increased plasma vitamin B12 concentrations were observed in all sheep. Blood selenium concentrations were also high during the experiment thereby preventing the evaluation of the glass bullet as a source of selenium.     

Serum copper concentrations in beef cows and heifers

OBJECTIVE: To characterize serum copper status of cows and heifers in beef cow-calf herds throughout the United States and to evaluate use of copper supplements in those herds. DESIGN: Cross-sectional survey. ANIMALS: 2,007 cows and heifers from 256 herds in 18 states. PROCEDURES: Producers participating in a health and management survey conducted as part of the National Animal Health Monitoring System voluntarily allowed serum samples to be obtained from cows and heifers for determination of copper concentration. Results were categorized as deficient, marginally deficient, or adequate. The proportion of cattle and herds (on the basis of mean value of the tested cattle) in each category was determined. Copper concentrations were compared between herds that reportedly used copper supplements and those that did not. RESULTS: Overall, 34 of 2,007 (1.7%) cows and heifers were deficient in copper, and 781 (38.9%) were marginally deficient. In each region, at least a third of the cattle were deficient or marginally deficient. For herds, 92 of 256 (35.9%) were marginally deficient, and 22 (0.8%) were deficient. Approximately half of the producers reported use of copper supplements, but a sizeable proportion of those producers' cattle and herds were classified as marginally deficient or deficient. CONCLUSIONS AND CLINICAL RELEVANCE: Copper deficiency is not restricted to a single geographic region of the United States. Copper deficiency can persist despite reported use of supplements by producers. Veterinarians dealing with beef cow-calf herds that have problems consistent with copper deficiency should not rule out copper deficiency solely on the basis of geographic region or reported use of copper supplements for the herd.     

The use of copper levels in hair to diagnose hypocuprosis

The possibility of using hair to help diagnose hypocuprosis was investigated. Diets containing different levels of molybdenum and sulphur were fed to nine Hereford steers. Liver reserves of copper were depleted rapidly when dietary levels of molybdenum and sulphur exceeded 2.7 mg/kg and 3.8 g/kg respectively. Following the onset of diarrhoea, liver reserves of copper were repleted by injecting copper glycinate. Samples of liver, blood and hair were collected at regular intervals and analysed for copper. Progressive changes in liver levels of copper were closely paralleled by changes in copper levels in hair and plasma. Relationships between copper levels in liver and plasma, and the liver and hair were both shown to be asymptotic. Plasma and hair levels were sensitive to changes in liver reserves below about 20 microgram/g, but changed little above this level. Sampling variation was shown to be less with hair than with plasma. It was concluded that copper levels in hair are a useful diagnostic aid in detecting hypocuprosis. Hair provides an integrated record of copper availability during its period of growth, and thus may be preferred to blood plasma which represents only a spot sample in time.     

Ceruloplasmin as an indicator of copper status in cattle and sheep.

The relationship between ceruloplasmin, a metalloenzyme with oxidase activity, and copper was investigated in cattle and sheep. The oxidase activity of ceruloplasmin correlated closely with the serum or plasma copper concentrations in cattle. The respective correlation coefficients were 0.83 and 0.60. In sheep serum, a correlation coefficient of 0.92 was obtained. In each instance, the relationship remained linear from the deficient to the high normal ranges of copper. Comparison of the linear regression relationships indicated the ceruloplasmin activity in bovine serum was statistically lower than the activity in bovine plasma (P less than 0.0001), through the intercepts from the regression lines of the two relationships were similar (P = 0.412). Comparisons of ovine and bovine serum-ceruloplasmin relationships indicated that a significant species difference was present. Ovine ceruloplasmin activity increased more rapidly as compared to the corresponding bovine activity over the range of copper concentrations investigated (P less than 0.0001). The intercept from the ovine regression relationship was also lower (P less than 0.0001). A correlation coefficient of 0.35 was observed between the serum ceruloplasmin activity and hepatic copper concentrations in cattle indicating that the mathematical relationship was not as well defined. Ceruloplasmin activity appears to correlate more closely with serum or plasma copper concentrations as compared to corresponding liver copper concentrations.     

Comparison of copper heptonate with copper oxide wire particles as copper supplements for sheep on pasture of high molybdenum content

OBJECTIVE: To assess the effectiveness of intramuscular injection of copper heptonate (CuHep) and an oral dose of copper oxide wire particles (COWP) in preventing Cu inadequacy in adult and young sheep on pasture of high Mo content. DESIGN: Field experiments with flocks of mature Merino wethers and crossbred weaners. PROCEDURE: Adult wethers were given 25 or 37.5 mg Cu as CuHep, 2.5 g COWP or no Cu treatment. The weaners were given 12.5 or 25 mg Cu as CuHep, 1.25 g COWP or no Cu treatment. At intervals over the next 12 (adults) or 8 (weaners) months the sheep were weighed and samples of blood and liver were collected for trace element assay. Wool samples collected from the adults at the end of the experiment were assessed for physical characteristics. RESULTS: The higher dosage of CuHep raised liver Cu above control group values for at least 9 months in adults and 3 months in weaners. The lower dosage of CuHep was similarly effective for 3 months in adults but was without effect in weaners. In adults the response to COWP matched that to the higher dosage of CuHep; in weaners it was greater, lasting at least 5 months. No changes indicative of Cu deficiency, apart from a depressed body weight in adults, were seen. CONCLUSIONS: In sheep on pasture of high Mo content a single intramuscular injection of CuHep providing 37.5 mg Cu to adults or 25 mg Cu to weaners will raise liver Cu reserves for at least 9 and 3 months respectively and may be an acceptable alternative to COWP for preventing seasonal Cu deficiency in sheep in southern Australia.     

Minimal herd sample size for determination of blood copper status of cattle

Copper is required by cattle for synthesis of numerous proteins and enzymes. Copper deficiency in cattle results in a variety of signs ranging from weight loss to diarrhea. In the fall of 1984 and 1985, blood samples were collected from 22 cattle herds near Gunnison, Colo. Approximately one third of the herds were classified as copper deficient (ie, mean serum copper concentration less than 0.6 mg/L). The inherent variability of serum copper concentrations within a herd mandates the determination of the minimal number of cattle to be tested to properly assess the blood copper status of a herd. Coefficients of variation for serum copper concentration were used to calculate a minimal sample size, with a 95% confidence interval for each herd. Minimal sample size ranged from 3 to 55 cattle/herd (ie, 1 to 22% of the herd); this finding suggested that the usual procedure of testing 10% of the herd may be inappropriate.     

Parenteral methods of supplementation with copper and selenium

Parenteral treatments can provide a rapid successful method of supplementing ruminants with copper and selenium, and avoid the possible interactions between an oral supplement and other dietary constituents. The copper preparations studied contained copper complexed with calcium edetate (EDTA) or copper methionate , copper oxide or copper oxyquinoline sulphonate. The recommended doses of these commercial preparations contain different amounts of copper only part of which is transferred to the liver stores from which it can be released during the following months. The recommended dose of copper oxyquinoline sulphonate contains only 12 mg copper and the duration of its protective effect is short. Only a small proportion of the copper in copper methionate and copper oxide is transferred to the liver whereas nearly all the copper in a single dose of the EDTA complex (50 mg copper for sheep) is transferred to the liver stores. Although no longer recommended for use in sheep the copper EDTA complex can be administered to cattle to provide up to 1 mg copper/kg bodyweight. Selenium deficiency in both cattle and sheep can be corrected by the subcutaneous administration of up to 0.15 mg selenium/kg bodyweight as sodium selenate. However, if a dietary deficiency persists copper and selenium treatments are effective for only a few months. To avoid the need for repeated treatments, slowly dissolving or controlled release systems have been developed. Subcutaneous depots of barium selenate have been used (1 mg selenium/kg bodyweight) but large residues remained at the site of injection for up to three months. Initial trials with controlled release glasses containing copper have shown that they maybe useful for routine parenteral therapy.     

A convenient method for the treatment of chronic copper poisoning in sheep using subcutaneous ammonium tetrathiomolybdate

Effective control of copper poisoning in sheep was obtained by the subcutaneous injection of ammonium tetrathiomolybdate. Three doses, each of 3.4 mg/kg bodyweight, were given on alternate days. This treatment caused a substantial reduction in liver copper content and in liver damage. It also decreased the mortality rate in animals that had developed the haemolytic crisis. The subcutaneous route is as effective as the intravenous route and is more convenient. No adverse side-effects of the treatment were observed.     

The effect of pig farming on copper and zinc accumulation in cattle in Galicia (north-western Spain)

Copper and zinc are frequently added at high concentrations to pig diets as growth promoters. Livestock grazing pasture contaminated with pig slurry may, therefore, be at risk from excessive intake of these elements. High liver copper concentrations have been detected in cattle from the agricultural region of Galicia (NW Spain), especially where there is intensive pig farming. The aim of this study was to evaluate whether pig farming does affect accumulation of copper and zinc in cattle in Galicia. Hepatic copper and zinc concentrations in calves were elevated in areas with naturally high levels of these elements in the soil. The densities of young pigs (piglets and growing-finishing pigs), but not reproductive sows, also influenced copper accumulation in calves. Liver copper levels in calves were significantly and positively related to the density of young pigs in the region. In areas with the highest pig densities, more than 20% of the cattle analysed had hepatic copper concentrations that exceeded the potentially toxic concentration of 150 mg/kg fresh weight. There was no evidence that zinc accumulation in calves was affected by pig density.     

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.     

Comparison between parenterally administered copper complexes of their ability to alleviate hypocupraemia in sheep and cattle

In a comparison of four parenteral copper preparations for sheep administered at similar dose rates, copper as diethylamine oxyquinoline sulphonate (copper DOS) was found to alleviate hypocupraemia in ewes more consistently than copper calcium EDTA and copper-methionate, given in a cream (C) or aqueous base (A). In similar comparisons of preparations for cattle, copper calcium EDTA was 19 per cent more effective than copper DOS and 36 to 48 per cent more effective than copper methionate (A). Methionate preparations were characterised by marked reactions at and slow translocation from the site of injection whereas copper DOS was rapidly translocated and gave little or no tissue reaction in sheep or cattle. Attributes of an improved parenteral copper preparation are discussed in the light of disadvantages of existing preparations.     

Copper,Zinc and Molybdenum in Livers of Norwegian Cattle At Slaughter

The concentrations of copper, zinc and molybdenum were measured in samples of cattle liver from 10 slaughter-houses in Norway. A total of 335 samples were analysed. A clear accumulation of copper with age was found, the average copper level in the younger animals (≦ 3 years, n = 194) being 30 µg Cu/g liver wet weight, and in the older ones (> 3 years, n = 141) 59 µg Gu/g. The range in the copper values found was considerable, though significant differences between some of the districts were recorded. Copper concentrations were classified as low (≦10 µg Gu/g) in 9.6 % of the samples. Zinc showed no accumulation with age, nor were there any differences in zinc levels found in animals from different districts, the average level being 32 µg Zn/g liver wet weight. The picture was the same for molybdenum, no differences between age groups or districts being found. The average level was 1.0 µg Mo/g liver. There was no significant correlation between levels of copper, zinc or molybdenum.The supply of copper and zinc to cattle in Norway seems close to sufficient, but copper- and zinc-fortified mineral supplementation of cattle feed is still to be recommended. There seems to be no need for molybdenum supplementation in cattle.