Chronic Copper Poisoning In Sheep Research Articles

Molybdenum-associated Pituitary Endocrinopathy in Sheep Treated with Ammonium Tetrathiomolybdate

Ammonium tetrathiomolybdate (TTM) has hitherto been the treatment of choice for chronic copper poisoning in sheep, but the long-term consequences have not been evaluated. This study was based on a flock of copper-poisoned sheep which, after apparently successful treatment with TTM, became infertile and progressively unthrifty and eventually died 2–3 years later. The last five surviving animals were subjected to euthanasia and detailed study. Necropsy revealed marked wasting together with depletion of the pituitary and adrenal glands, testicular atrophy and ovarian cystic follicles. Histopathological examination revealed a non-inflammatory atrophy or degeneration of the adenohypophysis with loss of trophic cells; adrenocortical and testicular atrophy and ovarian degeneration. The regressive changes in the anterior lobe of the pituitary were confirmed by immunocytochemical labelling, which revealed a marked depletion of adrenocorticotrophic hormone (ACTH), follicle stimulating hormone (FSH) and luteinizing hormone (LH) in the affected pituitaries by comparison with healthy controls. Excess molybdenum (Mo) retention ( P<0.02) was identified by inductively coupled plasma mass spectrometry (ICPMS) in the pituitaries and atomic absorption spectrometry (AAS) in the adrenals and brains of affected sheep. It was concluded that molybdenum introduced systemically as TTM is retained within the brain, pituitary and adrenal glands and is associated with a toxic endocrinopathy. It is postulated that Mo administered as thiomolybdate adversely affects the hypothalamo-adenohypophyseal system by interfering with trophic hormone release, leading to the cessation of reproductive activity and ultimately the failure of intermediary metabolism. Whether Mo exerts its effect centrally or directly on the pituitary was not established.

Antioxidant capacity of erythrocytes from sheep chronically poisoned by copper

Some indicative factors of antioxidant capacity in erythrocytes from chronic copper poisoning in sheep, were evaluated. Levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, reduced glutathione (GSH) and response to oxidative shock have been determined in animals with high and normal copper status. High copper status might have limited the SOD activity and induced lowest levels of GSH. This was associated with an increase of TBA reactivity in lipid peroxidation induced by hydrogen peroxide. In addition, GSH-Px activity did not differ significantly from that of control sheep. Our results demonstrate a direct correlation between the level of serum copper and a decrease in the evaluated antioxidant mechanisms. It is reasonable to postulate that non-specifically bound copper could be involved in cellular injury.

Chronic copper poisoning in sheep grazing pastures fertilized with swine manure

Chronic copper poisoning in sheep grazing pastures fertilized with swine manure

Variations in the intralobular distribution of copper in the livers of copper-loaded rats in relation to the pathogenesis of copper storage diseases

There are differences in the hepatic intralobular distribution of copper in copper storage related diseases which may be of pathogenetic significance. Male rats fed a high copper diet (1500 ppm) for 16 weeks were killed at intervals in an attempt to compare copper distribution in their livers with those in human, canine and ovine copper toxicosis. Copper was found to accumulate almost exclusively in the periportal and mid-zones of the rat liver lobules and was associated with progressive pathological changes which included focal and periportal degeneration and necrosis. This pattern of copper distribution contrasts markedly with the centrilobular retention reported in familial canine copper toxicosis and chronic copper poisoning in sheep which suggests that, in these conditions, a secretory deficiency may be less important than a metabolic zonal defect of intracellular copper metabolism. The pathological changes observed in copper-loaded rats have a different micro-anatomical localization from those in dogs and sheep, but show similarities to the early changes reported in the latter species and indicate the possibility of a similar cellular lesion.

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.

Levels of Copper, Molybdenum, Sulphur, Zinc, Selenium, Iron and Manganese in Native Pasture Plants from a Mountain Area in Southern Norway

Abstract The contents of copper (Cu), molybdenum (Mo), sulphur (S), zinc (Zn), selenium (Se), iron (Fe), manganese (Mn) and the Cu/Mo ratio were determined in different native plant species from a mountain area of central southern Norway. The overall mean values and ranges (mg/kg DM) were Cu: 6.0, 0.9–27.2; Mo: 0.25, 0.01–3.57; Zn: 77, 8–320; Se: 0.05, less than 0.01–0.32; Fe: 208, 15–2245; Mn: 338, 31–3784; S: (g/100 g DM) 0.20, 0.03–0.56; Cu/Mo: 79, 1–795. Levels of the individual elements showed considerable variability, both between and within plant groups. Mineral contents were compared with the established requirements for sheep and cattle, the following conclusion being drawn: Most of the mountain pasture plants investigated were deficient in copper and marginally low and partly deficient in molybdenum. The Cu:o ratios were generally high, and may explain the occurrence of chronic copper poisoning in sheep after grazing such pastures. All plant groups except lichens and sedges were found to contain...

Hepatogenous chronic copper poisoning in sheep associated with grazing Echium plantagineum.

Hepatogenous chronic copper poisoning in sheep associated with grazing Echium plantagineum.

Intravenous administration of thiomolybdate for the prevention and treatment of chronic copper poisoning in sheep.

1. Twenty-six sheep were used in experiments designed to test the effectiveness of ammonium tetrathiomolybdate in the prevention and treatment of chronic copper poisoning. 2. Intravenous injections of 100 mg ammonium tetrathiomolybdate twice weekly (a) prevented the occurrence of haemolytic crisis in sheep repeatedly dosed with copper sulphate and (b) minimized tissue damage and prevented further haemolytic crisis when given to sheep already in haemolysis. 3. Thiomolybdate prevented excessive deposition of Cu in the liver of sheep receiving orally large amounts of Cu and decreased liver Cu levels in sheep that were not given additional Cu. In the latter sheep, 50 mg ammonium tetrathiomolybdate given twice weekly did not produce histologically-detectable tissue damage even though liver and kidneys contained high levels of molybdenum, and kidneys contained elevated levels of Cu. 4. It is concluded that chronic Cu poisoning can be successfully prevented or treated by intravenous injection of appropriate doses of ammonium tetrathiomolybdate.

Chronic copper poisoning of sheep in Nigeria.

An outbreak of chronic copper poisoning in sheep is described. At least 145 out of 687 sheep (21.1%) on a government farm died during a period of 2 months. The clinical and post-mortem picture was one of sudden, profound intravascular haemolysis and subsequent jaundice. Mortality approached 100%. Plasma copper levels ranged from 22 to 76 mumol/litre. There was no obvious source of exogenous copper. Possible causes of the elevated copper levels are discussed.

Creatine kinase release and muscle changes in chronic copper poisoning in sheep

Chronic copper poisoning was induced in sheep by repeated dosing with an aqueous solution of copper sulphate. A sudden rise in the level of plasma creatine kinase (CK) occurred at haemolysis but the level returned to normal once the 'crisis' was over. The level of CK in the cerebrospinal fluid remained normal throughout the experiments. An isoenzyme study showed that the CK was liberated from muscle. Light microscopic studies failed to reveal consistent changes in muscle structure but ultrastructural changes in mitochondria, similar to those described as the earlies changes in muscle fibres in vitamin E deficiency, were seen in sheep killed during and after haemolysis. The elevations of CK levels and the mitochondrial changes were most marked in sheep that did not receive selenium and vitamin E supplements. It is suggested that the CK release at haemolysis may occur because of a transient increase in the permeability of muscle membranes which may be brought about by a number of factors such as: (a) hypoxia, (b) hypercupraemia, (c) decrease in vitamin E and/or selenium content in blood and tissues.

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.

Chronic Copper Poisoning in Sheep. I. The Relationship of Methaemoglobinemia to Heinz Body Formation and Haemolysis during the Terminal Crisis

The values of haematocrit, total haemoglobin in plasma, methaemoglobin percentages in erythrocytes and plasma, the osmotic fragility of the erythrocytes, and the occurrence of Heinz bodies were investigated during the terminal crisis in 4 cases of experimental chronic copper poisoning in sheep. At the beginning of the crisis, which lasted for well over one day, 10-20 per cent methaemoglobin was detected in the erythrocytes, before any haemolysis occurred. Later on severe haemolysis developed, and maximum levels of haemoglobin in the plasma were close to 2.5 g/100 ml. During the haemolytic stage both methaemoglobin and haemoglobin were detected in the plasma at approximately the same proportions as in the erythrocytes. No changes were observed in the osmotic fragility of the red cells until the onset of the haemolysis. It is concluded that the methaemoglobin formation is mainly an intra-corpuscular process and that most of the methaemoglobin detected in plasma in chronic copper poisoning in sheep, comes from the erythrocytes.

Role of pentose-phosphate pathway in haemolytic crisis of chronic copper toxicity of sheep

Although the rise in blood copper is associated with onset of the acute haemolytic crisis of chronic copper poisoning in sheep, the sudden fall in erythrocyte glutathione is apparently not due to a direct action of the copper. Moreover the reduced glutathione of the red cells is converted to some form that is not capable of regeneration by the pentose-phosphate mechanism. Only negligible inhibition of the pentose-phosphate enzymes occurs. As the haemolysis proceeds, there is a rapid recovery of erythrocyte glutathione levels, and a marked increase in pentose-phosphate enzyme activity, consistent with influx of young red cells. It seems that the release of copper into blood from liver at the haemolytic crisis is associated with an increase of the oxidative state of the blood, possibly by simultaneous release of other components from the liver.

Letter: Methemoglobinemia in acute copper sulfate poisoning.

Letters1 February 1975Methemoglobinemia in Acute Copper Sulfate PoisoningK. S. CHUGH, M.D., P. C. SINGHAL, M.D., B. K. SHARMA, M.D.K. S. CHUGH, M.D.Search for more papers by this author, P. C. SINGHAL, M.D.Search for more papers by this author, B. K. SHARMA, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-82-2-226_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAlthough Todd and Thompson had recorded methemoglobinemia in chronic copper poisoning in sheep in 1961 (1), the occurrence of methemoglobinemia in man has been reported only recently in two patients who, it was suspected, had had lethal acute copper intoxication during hemodialysis (2). The evidence of copper intoxication in these patients was circumstantial and retrospective; blood copper levels were not measured in either of them. We wish to report a case of methemoglobinemia in acute copper sulfate poisoning in a patient who came under our observation recently, with direct evidence of copper poisoning.A young man, aged 27 years, was...

Effect of copper on red cell glutathione and enzyme levels in high and low glutathione sheep.

SummaryEffects of copper on red cell glutathione and enzyme levels were investigated in sheep of high- and low-glutathione types. No significant differences were observed in copper induced inhibition of glutathione regeneration or erythrocyte enzyme activities in the two groups of sheep. These results, together with those showing the effect of copper on GSH oxidation suggest that low-glutathione sheep should not be more sensitive to small doses of copper, commonly encountered in chronic copper poisoning in sheep than are high-glutathione sheep.

Observations on Serum Adenosine Deaminase Activity in Experimentally Produced Liver Diseases of Cattle and Sheep: Yellow-Wood, Lantana, Carbon Tetrachloride and Chronic Copper Poisoning

Serum adenosine deaminase activity was studied in four cases of yellow-wood poisoning and five cases of lantana poisoning in cattle and also four cases of both carbon tetrachloride and chronic copper poisoning in sheep. In each of these liver diseases marked elevations of SAD activity were observed. The levels observed in cases of yellow-wood poisoning were considerably greater than those in the other liver conditions, this difference was discussed in relation to lesions in other organs in yellow-wood poisoning. L’activité de la désaminase adénosive dans le sérum a été étudiée dans 4 cas d’empoisonnement par le santal et 5 cas d’empoisonnement par le lantanier chez le bétail, et aussi 4 cas d’empoisonnement par le tétrachlorure de carbone et par le cuivre (chronique) chez les moutons. Dans chacune de ces maladies du foie on a observé une augmentation marquée de l’activité de la désaminase adénosive dans le sérum. Les niveaux observés dans les cas d’empoisonnement par le santal étaient considérablement plus élevés que ceux correspondant aux autres conditions hépatiques, cette différence fit l’objet d’une étude au sujet de lésions d’autres organes lors de l’empoisonnement par le santal. Die Serumadenosindeaminasetätigkeit wurde bei vier Rindern mit Visetholzvergiftung und fünf Rindern mit Lantanavergiftung sowie bei vier Schafen mit Tetrachlorkohlenstoff- und chronischer Kupfervergiftung untersucht. Die SAD-Tätigkeit war bei allen diesen Leberstörungen beträchtlich erhöht. Bei den Fällen mit Visetholzvergiftung wurden bedeutend höhere Spiegel beobachtet als bei den anderen Leberstörungen, und dieser Unterschied wird im Zusammenhang mit der Schädigung anderer Organe durch eine Viset olzvergiftung diskutiert. La actividad de la adenosina desaminasa sérica fue estudiada en cuatro casos de envenenamiento con fustete y en cinco casos con lantana en ganado vacuno y también caatro casos en ovejas que fueron envenenadas con tetracloruro de carbono y con cobre-. En cad: una de estas enfermedades hepáticas se encontró marcada elevación de la adenosina desaminasa sérica. Los niveles encontrados en los casos debidos a envenenamiento con fustete fueron considerablemente mayores que en los otros. Se discute esta diferencia en relación a las lesiones en otros órganos encontrados en los casos debido a envenenamiento con fustete.

Observations on Blood Copper in the Sheep : II.—Chronic Copper Poisoning

SUMMARY A detailed study of blood copper in 4 cases of induced chronic copper poisoning in sheep was made. The development of chronic copper poisoning followed a pattern of 3 stages, according to the level of whole blood copper attained. Apart from transient elevation of the RBC Cu level no marked changes occurred during Stage I which lasted from 62 to 104 days. During Stage II an increase in whole blood copper to about twice normal levels was accompanied by a change in plasma colour due to bilirubin, a decrease in liver function and changes in the level of haematocrit. The blood copper levels were a result of changes in both RBC Cu and DR Cu. The excess copper (up to 19 µg./ml.) present in the blood during the crisis of Stage III was seen first in the plasma, as DR Cu, and later in the red blood cells. These changes are comparable in nature, though not in duration, with those which arc observed after a single massive dose of copper. It would appear that the inability of the red blood cell to release its extra copper is responsible, in part, for the level of whole blood copper and the time for which this level persists. The immediate cause of death in 2 of these sheep would appear to have been the acute general toxic effect of copper, while in the other 2, anaemia and uraemia may well have played an additional part.