scholarly journals Copper Supplementation, A Challenge in Cattle

Animals ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1890
Author(s):  
Marta López-Alonso ◽  
Marta Miranda
Keyword(s):  
Copper Deficiency ◽  
Copper Toxicity ◽  
Copper Metabolism ◽  
Copper Accumulation ◽  
Hepatic Copper ◽  
Copper Status ◽  
Large Numbers ◽  
Copper Supplementation ◽  
Key Points ◽  
Copper Storage

Ensuring adequate copper supplementation in ruminants is a challenging task due to the complexity of copper metabolism in these animals. The three-way interaction between copper, molybdenum and sulphur (Cu-Mo-S) in the rumen makes ruminants, particularly cattle, very susceptible to suffering from secondary copper deficiency. Paradoxically, excessive copper storage in the liver to prevent deficiency becomes a hazard when ruminants are fed copper-supplemented diets even slightly above requirements. While cattle were traditionally thought to be relatively tolerant of copper accumulation, and reports of copper poisoning were until recently somewhat rare, in recent years an increased number of episodes/outbreaks of copper toxicity in cattle, particularly in dairy cattle, have been reported worldwide. The growing number of lethal cases reported seems to indicate that copper intoxication is spreading silently in dairy herds, urging the development of strategies to monitor herd copper status and improve farmers’ awareness of copper toxicity. In fact, monitoring studies carried out on numerous samples collected from culled animals in slaughterhouses and/or diagnostic laboratories have demonstrated that large numbers of animals have hepatic copper concentrations well above adequate levels in many different countries. These trends are undoubtedly due to copper supplementation aimed at preventing copper deficiency, as dietary copper intake from pasture alone is unlikely to cause such high levels of accumulation in liver tissue. The reasons behind the copper overfeeding in cattle are related both to a poor understanding of copper metabolism and the theory of “if adding a little produces a response, then adding a lot will produce a better response”. Contrary to most trace elements, copper in ruminants has narrow margins of safety, which must also be formulated considering the concentrations of copper antagonists in the diet. This review paper aims to provide nutritionists/veterinary practitioners with the key points about copper metabolism in cattle to guarantee an adequate copper supply while preventing excessive hepatic copper loading, which requires à la carte copper supplementation for each herd.

Studies on copper and cobalt therapy of cattle in central coastal Queensland

1967 ◽  
Vol 18 (1) ◽  
pp. 169 ◽  
Author(s):  
GI Alexander ◽  
JM Harvey ◽  
JH Lee ◽  
WC Stubbs
Keyword(s):  
Growth Response ◽  
Copper Deficiency ◽  
Copper Metabolism ◽  
Subcutaneous Injections ◽  
Liver Copper ◽  
Copper Status ◽  
Period 2 ◽  
Copper Supplementation ◽  
Copper Therapy ◽  
Effect Of Copper

Four experiments described determined the effect of copper and cobalt therapy on the growth and productivity of cattle on the marine plains of central coastal Queensland. Copper was administered by subcutaneous injections of copper glycinate, and cobalt by dosing per os with heavy cobalt pellets. The growth of weaned cattle was significantly improved by copper, particularly from June to October when limited palatable feed on the high ground forced the animals to forage on the para grass swamps. During the same period, 2-year-old heifers also showed a growth response to copper. Their conception rate increased after 19 months of copper therapy but not after 10.5 months. The growth rate of their calves bas significantly increased by copper supplementation. Liver copper concentrations were always low in untreated cattle. Copper therapy maintained these reserves at higher levels, which varied according to the season and the rate of growth of the animals. Calves born to treated cows had higher initial liver copper reserves than those from untreated cows, but in the absence of copper therapy these reserves declined to low and comparable levels in all calves at weaning. Pasture analyses suggest that the copper deficiency revealed was due to interference with copper metabolism rather than to a low copper status in the diet; this interference did not appear to be due to molybdenum. Weaned cattle appeared to respond to cobalt during 1960 but not subsequently, while the cows and calves showed no response. The vitamin B12 status in liver and serum appeared adequate in both treated and untreated cattle.

Copper oxide particles for grazing sheep

1983 ◽  
Vol 34 (6) ◽  
pp. 751 ◽  
Author(s):  
JP Langlands ◽  
JE Bowles ◽  
GE Donald ◽  
AJ Smith ◽  
DR Paull ◽  
...  
Keyword(s):  
Copper Oxide ◽  
Dose Rate ◽  
Copper Toxicity ◽  
Dose Rates ◽  
Hepatic Copper ◽  
Copper Status ◽  
Oxide Particles ◽  
Grazing Sheep ◽  
Copper Storage ◽  
Rate Of Decline

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.

The effect of molybdenum, sulphur and iron on the copper status of store lambs

2000 ◽  
Vol 2000 ◽  
pp. 88-88
Author(s):  
A.M. Mackenzie ◽  
S Evans ◽  
J.N.C. Lynn ◽  
D.V. Illingworth ◽  
R.G. Wilkinson
Keyword(s):  
Copper Deficiency ◽  
Clinical Signs ◽  
Copper Metabolism ◽  
Mineral Deficiency ◽  
Copper Status ◽  
Biochemical Indicator ◽  
Copper Supplementation ◽  
The World ◽  
Plasma Copper ◽  
Accurate Indicator

Clinical copper deficiency is the second most common mineral deficiency in the world, the main cause being high dietary levels of molybdenum, sulphur and iron. Phillippo et al, (1987) reported that clinical signs of deficiency resulted from high dietary Mo and S. However, Fe and S resulted in hypocupraemia but did not induce clinical signs of deficiency. Therefore is was concluded that clinical copper deficiency was due to a direct effect of dietary Mo and S on copper metabolism in ruminants. Mackenzie et al. (1997) reported that plasma copper levels were not an accurate indicator of copper status and unlikely to predict animals requiring copper supplementation. Caeruloplasmin is large copper enzyme and accounts for 88% of plasma copper and Mackenzie et al. (1997) proposed that a caeruloplasmin to plasma copper ratio may provide a more accurate biochemical indicator of copper status. This trial was designed to investigate the effect of dietary Mo, S and Fe on the copper status of the lambs.

A Perspective on Copper and Liver Disease in the Dog

2000 ◽  
Vol 12 (2) ◽  
pp. 101-110 ◽  
Author(s):  
Larry P. Thornburg
Keyword(s):  
Liver Disease ◽  
Storage Disease ◽  
Copper Metabolism ◽  
Normal Liver ◽  
Clinical Problem ◽  
Normal Function ◽  
Copper Accumulation ◽  
Hepatic Copper ◽  
Copper Storage ◽  
End Stage

Copper is a ubiquitous trace metal necessary for normal function of a variety of cellular proteins. Intracellular copper metabolism is complex, and only a few of the proteins/genes involved are known. Copper deficiency does not appear to be a clinical problem in dogs. Excess copper accumulation in the liver as a cause of hepatitis and cirrhosis was first demonstrated among Bedlington terriers. Subsequently, copper accumulation in the liver has been shown to occur in several other breeds of dogs. Excess hepatic copper has been found in dogs with normal liver histology, dogs with hepatitis, and dogs with end stage cirrhosis. Evidence is accumulating that copper is a cause of liver disease in breeds of dogs other than Bedlington terriers. Moreover, as more data are accumulated, the copper storage disease appears to have characteristics that are very similar among all of the affected breeds.

Copper responsive infertility in British cattle: the use of a blood caeruloplasmin to copper ratio in determining a requirement for copper supplementation

2001 ◽  
Vol 26 (2) ◽  
pp. 429-432 ◽  
Author(s):  
N. R. Kendall ◽  
D. V. Illingworth ◽  
S. B. Telfer
Keyword(s):  
Copper Deficiency ◽  
Reference Ranges ◽  
Copper Status ◽  
Veterinary Surgeons ◽  
Copper Supplementation ◽  
Plasma Copper ◽  
Veterinary Laboratory Agency ◽  
Ruminant Animals ◽  
The University ◽  
Female Cattle

AbstractSigns of clinical copper deficiency in ruminant animals include infertility. Blood copper concentrations alone are not an adequate indicator of copper status, as they take no account of the thiomolybdate challenge to the animal. The use of the ratio of caeruloplasmin activity to plasma copper concentration should provide a better indicator of molybdenum induced copper problems. The objectives of this study were to obtain veterinary feedback on the University of Leeds Trace Element Laboratory's (ULTEL) assessment of copper status and responses to any recommended supplementation. Blood samples from 713 female cattle from 114 herds were assessed for copper status, including plasma copper concentrations, serum caeruloplasmin activities and the ratio between the caeruloplasmin and plasma copper (CP/PlCu ratio). On the basis of only plasma copper analysis 95.0 % of the cattle were classified as being of normal copper status using Veterinary Laboratory Agency reference ranges. However, when the CP/PlCu ratio was also considered only 35.6 % of the cattle would be classed as having normal copper status. Appropriate copper supplementation would be required by 30.7 % of the cattle and a further 27.8 % could also benefit from additional copper. Veterinary responses to a questionnaire (80 % returned) indicated that infertility was a major problem in their clients’ herds. Where copper supplementation was recommended and administered an increase infertility was observed. In herds showing poor or lack ofoestrous behaviour/ later embryo loss (signs of clinical copper deficiency), 91.7 % reported that these signs were reduced by copper supplementation. The relevance of the CP/PlCu ratio as a diagnostic aid in the identification of copper responsive infertility has been supported by the responses of the veterinary surgeons.

Effect of chelators on copper metabolism and copper pools in mouse hepatocytes

1989 ◽  
Vol 256 (4) ◽  
pp. G667-G672
Author(s):  
H. J. McArdle ◽  
S. M. Gross ◽  
I. Creaser ◽  
A. M. Sargeson ◽  
D. M. Danks
Keyword(s):  
Metal Ion ◽  
Chelation Therapy ◽  
Copper Metabolism ◽  
Copper Accumulation ◽  
Copper Uptake ◽  
Mouse Hepatocytes ◽  
Copper Chelators ◽  
Copper Storage ◽  
And Storage

Disorders of copper storage are usually treated by chelation therapy. It is generally thought that the chelators act by mobilizing copper from the liver, hence allowing excretion in the urine. This paper has examined the effect of chelators on copper uptake and storage in mouse hepatocytes. Penicillamine, a clinically important chelator, does not block the uptake of copper or remove copper from hepatocytes. Two other copper chelators, sar and diamsar, which form very stable and kinetically inert Cu2+ complexes by encapsulating the metal ion in an organic cage, were shown to block copper accumulation by the cells and to remove up to 80% of cell-associated copper. They also removed most (approximately 80%) of the 64Cu accumulated by the cells in 30 min, but released only a small percentage (less than 20%) of that accumulated over 18 h. The results show that copper in the hepatocyte can be divided into at least two pools, an easily accessible one, and another, not removable even after long-term incubation with any of the chelators. Most of the copper normally found in the cell appeared to be associated with the former pool.

scholarly journals Elesclomol restores mitochondrial function in genetic models of copper deficiency

2018 ◽  
Vol 115 (32) ◽  
pp. 8161-8166 ◽  
Author(s):  
Shivatheja Soma ◽  
Andrew J. Latimer ◽  
Haarin Chun ◽  
Alison C. Vicary ◽  
Shrishiv A. Timbalia ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Copper Deficiency ◽  
Copper Metabolism ◽  
Mitochondrial Respiratory Chain ◽  
Yeast Cells ◽  
Loss Of Function ◽  
Zebrafish Model ◽  
Pharmacological Agents ◽  
Copper Supplementation ◽  
Genes Encoding

Copper is an essential cofactor of cytochrome c oxidase (CcO), the terminal enzyme of the mitochondrial respiratory chain. Inherited loss-of-function mutations in several genes encoding proteins required for copper delivery to CcO result in diminished CcO activity and severe pathologic conditions in affected infants. Copper supplementation restores CcO function in patient cells with mutations in two of these genes, COA6 and SCO2, suggesting a potential therapeutic approach. However, direct copper supplementation has not been therapeutically effective in human patients, underscoring the need to identify highly efficient copper transporting pharmacological agents. By using a candidate-based approach, we identified an investigational anticancer drug, elesclomol (ES), that rescues respiratory defects of COA6-deficient yeast cells by increasing mitochondrial copper content and restoring CcO activity. ES also rescues respiratory defects in other yeast mutants of copper metabolism, suggesting a broader applicability. Low nanomolar concentrations of ES reinstate copper-containing subunits of CcO in a zebrafish model of copper deficiency and in a series of copper-deficient mammalian cells, including those derived from a patient with SCO2 mutations. These findings reveal that ES can restore intracellular copper homeostasis by mimicking the function of missing transporters and chaperones of copper, and may have potential in treating human disorders of copper metabolism.

Copper status of sheep grazing pastures fertilized with sulfur and molybdenum

1981 ◽  
Vol 32 (3) ◽  
pp. 479 ◽  
Author(s):  
JP Langlands ◽  
JE Bowles ◽  
GE Donald ◽  
AJ Smith ◽  
DR Paull
Keyword(s):  
Copper Sulfate ◽  
Copper Concentration ◽  
Sodium Molybdate ◽  
Sheep Grazing ◽  
Biopsy Technique ◽  
Black Sheep ◽  
Hepatic Copper ◽  
Copper Status ◽  
Copper Storage ◽  
Molybdenum Concentration

Varying quantities of sodium molybdate, superphosphate and copper sulfate were applied to 30 plots, and changes in hepatic copper concentration in sheep grazing these plots were measured by using a biopsy technique. A relationship between changes in hepatic copper storage and the copper and sulfur x molybdenum concentrations in the green forage on offer was calculated. This relationship was used to calculate the quantity of copper in green forage on offer necessary to maintain hepatic copper concentration constant when the forage varied in sulfur and molybdenum concentration. In a second experiment sodium molybdate was applied to pasture grazed by sheep at rates varying from 0 to 2000 g molybdenum per ha. Black sheep grazing pasture dressed with 2000 g molybdenum per ha, grew white wool for four months following molybdenum application; this corresponded to the period when molybdenum concentration in herbage on offer was greatest. There were also changes in blood, wool, kidney and liver composition following molybdenum application but these were small when molybdenum was applied at the usual commercial rate. The results of both experiments suggest that the application of molybdenum to pasture at commercial rates is unlikely to induce copper deficiencies in grazing sheep.

Oxidized copper wire particles for copper therapy in sheep

1982 ◽  
Vol 33 (6) ◽  
pp. 1073 ◽  
Author(s):  
GJ Judson ◽  
TH Brown ◽  
D Gray ◽  
DW Dewey ◽  
JB Edwards ◽  
...  
Keyword(s):  
Copper Oxide ◽  
Copper Wire ◽  
Significant Proportion ◽  
Clinical Signs ◽  
Copper Toxicity ◽  
Liver Copper ◽  
Copper Status ◽  
Copper Supplementation ◽  
Copper Therapy ◽  
Higher Doses

Ninety Merino weaner sheep were assigned to one of six groups on the basis of liveweight and liver copper concentrations. Sheep in four groups each received one oral dose of oxidized copper wire particles, viz. 2.5, 5, 10 or 20 g per animal. Sheep in another group each received a subcutaneous injection of 12 mg copper as diethylamino cupro-oxyquinoline sulfonate and another group of sheep did not receive any copper supplement. Liver copper concentrations responded positively to copper oxide load. The 2.5 g dose of copper oxide wire was more efficacious than the commercial injectable product in raising copper status, but the higher doses of oxide raised liver copper concentrations to values similar to those recorded in cases of copper poisoning. Copper concentrations in blood plasma, muscle and kidney were not altered by the copper load. No clinical signs, nor biochemical or histological evidence of acute copper toxicity, were found. Liver copper values fell in all sheep from 10 weeks after copper therapy until the end of the trial at 50 weeks post-therapy. Over this period of 40 weeks, the rate of mobilization of liver copper was linear and was positively related to the initial concentration of copper in the liver. A significant proportion of the oxidized copper wire dosed to sheep was recovered in the forestomachs and abomasa of selected sheep 4 weeks after dosing. No evidence of abomasal damage due to particles could be established. It is concluded that oral dosing of oxidized copper wire is a safe and effective method of copper supplementation to sheep.

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