Blood copper and serum enzyme changes following copper calcium E.D.T.A. administration to hill sheep of low copper status

Changes in blood copper and serum enzyme levels following copper calcium complex of ethylene diamine tetra acetic acid administration were studied in ewes in 3 hill flocks of low copper status and with a history of swayback. Blood copper levels increased within a few hours of injection in all the sheep and in some animals from 2 flocks there was a release of liver-specific enzymes into the blood 24 to 48 hours after dosing. Three animals died within 36 hours of injection.     

Diethylsuccinate carboxylesterase activity in sheep poisoned by copper

Plasma diethylsuccinate carboxylesterase activity in plasma was elevated within 7 days in 4 sheep which received 4 mg Cu per kg body weight in gelatin capsules daily for 100 days followed by the same amount of Cu as a drench until the haemolytic crisis commenced. Plasma aspartate amino-transferase and sorbitol dehydrogenase activities in plasma were not elevated in these animals until sixty days after the Cu treatment began. Activities of all 3 enzymes in the liver homogenates from copper-treated sheep were lower (P less than 0.01) than in control animals.     

Autophagy and apoptosis in liver during the prehaemolytic phase of chronic copper poisoning in sheep.

Fine structural changes in the liver during the prehaemolytic phase of chronic Cu poisoning in sheep were investigated in biopsy and post-mortem samples obtained from 24 Finn-Dorset × Suffolk ewe lambs. From the beginning of the prehaemolytic phase excessive accumulation of Cu was accompanied by sublethal injury to liver parenchymal cells, reflected by changes in the endoplasmic reticulum and an increase in the numbers of autophagic vacuoles. Towards the later stages of the prehaemolytic phase there was a high incidence of cell death and apoptosis.     

Experimental copper and heliotrope intoxication in sheep: morphological changes

Young Merino wethers were used to determine the effects of copper and heliotrope, fed together or separately, on the development of toxicity and the concentration of trace elements in the liver and kidney. In one experiment copper and heliotrope were given concurrently, in a second experiment heliotrope was fed for 12 weeks and copper administration commenced 8 weeks later. The 10 sheep fed heliotrope alone did not show signs of clinical illness but one died and was found to have severe liver damage. Eleven sheep were given copper alone and three developed the clinical signs and lesions of haemolysis. Fourteen sheep were given copper and heliotrope and 13 became ill. Of these, three developed haemolysis, eight became jaundiced and two became weak without developing jaundice. The concentrations of copper in the livers of control and heliotrope-treated sheep, were comparable. In the animals given copper alone, the concentration of copper in the liver was twice as high as that in controls and in those given heliotrope and copper, it was three times as high as in the liver of control sheep. Feeding heliotrope alone induced the histological changes of pyrrolizidine alkaloid toxicity in the liver, but this was not associated with an excessive accumulation of copper or the development of clinical illness. However, it did predispose the animals to the effects of a second toxin since giving heliotrope and copper concurrently, or giving copper subsequent to feeding heliotrope, markedly enhanced the toxicity of the two substances and caused an excessive accumulation of copper in the liver.     

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 beta-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.     

Correlation of zinc and copper values in the blood serum of Makuii sheep

In autumn 2009, 87 blood samples (28 male and 59 female) were taken, via jugular vein puncture using a heparinised venoject, from Makuii sheep in a preserved herd. The samples were divided into four age groups. Blood samples were transferred to a laboratory on ice, and the serum samples were separated from whole blood by centrifugation. Concentration of zinc and copper was measured in the serum by atomic absorption spectrophotometry. The mean?±?SE of zinc and copper was 8.34?±?1.07 and 12.32?±?0.28?μmol/l, respectively. Zinc values were less than the normal expected range (P?<?0.05), but the copper value was normal in serum samples. It is possible that there is zinc deficiency in the herd in this part of Iran.     

Comparing serum and hepatic concentrations of iron, copper, and cobalt in healthy sheep and sheep with chronic fasciolosis

Fasciolosis is one of the most important parasitic diseases of ruminants. This parasite causes liver dysfunction which may contribute to albumin synthesis and copper transferring to the liver and also reduces the elemental storage. Due to these reasons and to determine the effects of fasciolosis on serum and liver iron, copper, and cobalt status, the present study was conducted on 460 slaughtered sheep. During antemortem examination and after giving an identification number, blood samples were taken, and age, sex, and origin of animals were recorded. Visual inspection and palpation were performed on the liver to determine Fasciola infestation; then, liver samples were taken from 100 sheep (50 infested and 50 healthy ones), and the concentration of the mentioned minerals was measured by atomic absorption spectrophotometry. The results indicated that liver iron, copper, and cobalt concentrations in healthy sheep (74.47, 32.95, and 0.13 ppm, respectively) were significantly higher than those in sheep with fasciolosis (36.78, 11.22, and 0.05 ppm, respectively) (P?<?0.05). These findings may explain the role of hepatic injuries caused by fasciolosis on mineral status and also the role of minerals on parasite persistency.     

Effect of intravenously administered tetrathiomolybdate on plasma copper concentrations of copper-loaded sheep

Chronic copper toxicity was induced in 14 ewes in two groups by oral dosing with CuSO4. Copper dosing was stopped in sheep of groups 1 and 2 at the first rise of serum acid phosphatase activity and on the first day of haemolysis, respectively. Thiomolybdate was administered intravenously (i.v.) to sheep of group 2 at the rate of 100 mg on the first day of haemolysis and at 24-h intervals, with a maximum of 3 doses during haemolysis. Thiomolybdate was also given intravenously at a dose of 50 mg twice weekly for 11 weeks to four sheep of group 1 after the cessation of copper dosing (group 1B) and to five sheep of group 2 at the end of haemolysis. Plasma copper concentration was determined before and 24 h after each injection of 50 mg thiomolybdate and "elevations" of plasma copper concentration were seen after each injection of thiomolybdate. The differences between plasma copper concentrations observed before and after each thiomolybdate injection for doses 1 to 11 were significantly higher than those seen for doses 12 to 22. Following thiomolybdate administration, the copper content of the liver of sheep in groups 1B and 2 was reduced much more than in sheep of group 1A, in which copper dosing also ceased but which did not receive thiomolybdate. It was concluded that the high plasma copper response to thiomolybdate doses 1 to 11 was due to an influx of copper into the bloodstream from the heavily copper-loaded liver cells. The lower plasma copper response during the latter part of thiomolybdate administration was due to a gradual reduction in the amount of copper entering the bloodstream from the liver cells, as these cells became depleted of copper. Some of this copper may become part of the glomerular filtrate and be taken up by the cells of the proximal convoluted tubules of the kidney or may be excreted in the urine.     

Relationships between swayback incidence and concentration of copper in the blood of sheep of different breeds

In 2 flocks of sheep each comprising several breeds which had suffered differing losses from swayback in 1964, a comparison of blood Cu levels of ewes born in the swayback year and others born in years when swayback had not occurred suggested that swayback had removed the lambs with lower than average Cu levels, and that the consequences of this persisted into adulthood. The unaffected survivors as a group had a correspondingly higher average level of Cu in their blood.