Concentration of Selenium in Liver in Relation to Copper Level in Normal and Copper-Poisoned Sheep

Copper absorption, liver accumulation and development of copper toxicosis in sheep are influenced by a variety of other elements, in particular molybdenum, sulphur and zinc (Underwood 1977). In a previous study on liver concentrations of copper, molybdenum and zinc in normal and copper-poisoned sheep, no direct correlation was found between the concentrations of the three metals, but molybdenum was significantly lower in the livers from sheep dead from chronic copper poisoning than in normal animals (Frøslie & Norheim 1976).     

Chronic copper poisoning in two Holstein cows

Chronic copper poisoning with an acute hemolytic crisis is described in 2 mature Holstein dairy cows from separate herds. Toxic concentrations of copper were present in the serum and in liver and kidney tissues of each cow. There was no history of environmental or dietary exposure to excessive quantities of copper. No further clinical cases of chronic copper toxicosis were observed in the herds. As well as massive hemolysis, in both cows there was involvement of other organ systems including the liver and kidneys which contributed to the clinical course of the disease.     

Copper poisoning in a flock of sheep. Copper excretion patterns after treatment with molybdenum and sulfur or penicillamine

During an outbreak of chronic copper poisoning, fecal and urinary copper excretion were measured following treatment with molybdenum and sulfur supplementation of the feed (0.1 g ammonium molybdate plus 1 g sodium sulfate/sheep/day) or oral penicillamine (50 mg/kg bodyweight/day) using rams in metabolism cages. Serum glutamic-oxaloacetic transaminase activities and liver levels of molybdenum and copper in sheep that died were also monitored. Within four days of starting molybdenum and sulfur supplementation a highly significant increase in fecal copper excretion was evident and the increase persisted throughout the monitoring period (five weeks — general treatment of the flock continued for another three weeks). There was no effect of the molybdenum and sulfur supplementation on urinary excretion of copper. The molybdenum and sulfur supplementation was very effective, resulting in a rapid marked decrease in mortality. Oral penicillamine treatment induced cupruresis but did not affect fecal copper excretion. The results indicated that, while the cost of penicillamine may be a limiting factor for general treatment of a flock, it may be the drug of choice for the therapy of valuable breeding animals because cupruresis may be accurately and individually controlled. Serum glutamicoxaloacetic transaminase activities were a valuable aid in diagnosing chronic copper toxicosis as well as for monitoring recovery. High initial liver copper levels were gradually reduced following molybdenum and sulfur treatment. However, at the end of the study the liver copper levels of dead sheep varied within wide limits and there were still some sheep with high liver copper levels.     

The Concentrations of Molybdenum and Zinc in Liver in Relation to Copper Accumulation in Normal and Copper Poisoned Sheep

The concentrations of copper, molybdenum and zinc were measured in the liver of normal grazing sheep and lambs from Eastern Norway, and in sheep dead of chronic copper poisoning. The following mean values were found: Normal sheep: 173 ± 130 μg Gu/g wet weight, 1.0 ±0.3 μg Mo/g, and 49 ± 10 μg Zn/g; lambs: 129 ± 59 μg Gu/g, 0.9 ± 0.3 μg Mo/g, and 46 ±9 μg Zn/g; sheep dead of copper poisoning: 429 ± 249 μg Gu/g, 0.4 ± 0.1 μg Mo/g, and 43 ± 2d μg Zn/g. Sheep with low liver copper (Gu < 10 μg/g) were also analyzed for molybdenum and zinc, with the following results: 1.0 ± 0.2 μg Mo/g, and 45 ± 8 μg Zn/g wet weight. The differences in liver copper between all the groups, and the differences in molybdenum concentrations between the normal sheep and the lambs and between the normal sheep and the poisoned sheep were significant (P < 0.001). No significant correlations between liver copper/liver molybdenum or liver copper/liver zinc were detected.     

Copper poisoning in the Kruger National Park: field investigation in wild ruminants

Chronic copper poisoning was investigated in ruminants within the Phalaborwa area of the Kruger National Park (KNP). Exposure of ruminants to environmental copper pollution resulting form copper smelting operations of a mine in the area was examined by comparing impala faecal copper concentrations in dung heaps and tissue (liver, lung and kidney) copper concentrations of organs collected from impala and buffalo culled within three risk zones (high, moderate and low) of the study area in relation to the distance from the smelter over a period of 4 years. An additional area within the KNP not exposed to the environmental copper pollution from the mine served as control. Tissue copper accumulation was also determined in tracer impala placed in the highest risk zone. The results of this study confirmed the occurrence of chronic copper poisoning in impala and indicated an inverse relationship in extent of impala faecal copper elimination and in tissue copper accumulation in impala and buffalo with distance from the copper smelter. Impala liver copper concentrations were shown to be a reliable indicator of copper accumulation for these ruminants. The presence lung copper concentrations, indicating the exposure to airborne copper were the highest in impala culled in the zone closest to the smelter. Liver copper concentrations above the diagnostic limit of 150 ppm for chronic copper poisoning in domestic sheep were consistently found in impala within the highest risk zone. Clinical pathological measurements suggested that AST activity could possibly be used as an indicator for chronic copper poisoning in impala. It is concluded that, in addition to the environmental and geo-botanical evidence previously reported, the copper smelter of a nearby copper mine is the most likely source of copper pollution responsible for chronic copper poisoning in impala and the occurrence of high copper concentrations in buffalo in the Phalaborwa area of the KNP.     

Haemolytic crisis in sheep as a result of chronic exposure to copper

Usually practicing veterinarians and animal keepers have to deal with inadequate supplementation of copper which causes deficiency diseases. However, instead of curing, the consequential intake of copper is likely to cause copper intoxication. Copper poisoning is observed particularly frequently, in sheep--the most sensitive domestic animal to copper toxicity. In most cases, sheep undergo chronic exposure to copper causing liver necrosis and resulting in massive haemolysis, haemoglobinuria and eventually in renal failure. The observed symptoms have an acute character and a set of them is called haemolytic crisis. The pathogenesis, signs and diagnosis of this syndrome are described in this article.     

Copper toxicosis in a Boer goat

A 1‐year‐old female Boer goat was presented with a 1‐day history of pigmenturia, anorexia, and shivering. Anemia was not present initially, but progressive hemolytic anemia developed subsequently and was characterized by the finding of Heinz bodies in both intact RBCs and in ghost cells and the presence of atypical fusiform RBCs. Plasma biochemical analysis revealed increased activities of aspartate aminotransferase and gamma‐glutamyltransferase, hyperbilirubinemia, and azotemia. Histopathologic examination of a liver biopsy revealed necrosis of individual hepatocytes and intracytoplasmic rhodamine‐positive granules, consistent with copper. Copper concentration in ante‐mortem hepatic tissue was increased, and a diagnosis of copper toxicosis was made. Despite supportive therapy, the goat continued to decline and was euthanized. Necropsy findings included hepatic necrosis and hemoglobinuric nephrosis. Freshly collected specimens of liver and kidney had markedly increased copper concentrations. The mineral composition of the water, grass hay, and goat chow was evaluated, and toxins and significant mineral imbalances were not found. The underlying cause of the hepatic accumulation and subsequent release of copper remains unclear in this goat. Recently, Boer goats have been recognized as being prone to copper toxicosis and may be more susceptible than other breeds; similar to sheep, Boer goats may experience a hemolytic crisis secondary to copper toxicosis.     

Chronic copper poisoning in sheep grazing pastures fertilized with swine manure

Several pregnant ewes developed an acute hemolytic crisis and died. Liver and kidney copper concentrations were high, confirming chronic copper poisoning as the cause of death. Feed and water samples that the affected ewes had been consuming did not contain excess copper. Because swine manure slurry had been applied to the pasture where the sheep had grazed, a copper analysis was conducted on soil and forage samples from this field. High copper concentrations were detected in the soil and forage samples from the slurry pasture. Most sheep producers are aware of the catastrophic consequences that result when feeds containing copper and insufficient amounts of molybdenum are fed to sheep. However, producers and veterinarians often are unaware of some of the subtle sources of copper. Most of the copper that is added to swine and poultry feeds as growth promotants passes through the gastrointestinal tract unabsorbed and remains in the waste material. Pastures that have copper-containing waste material, but no molybdenum applied, can produce the same fatal results as giving sheep feed supplemented with copper but containing no molybdenum.     

Copper toxicity in confinement-housed ram lambs.

Fourteen Suffolk rams (6 mo) were diagnosed with chronic copper poisoning. Preliminary results indicated that a combination of serum aspartate aminotransferase, gamma glutamyltransferase, and copper could be used as a test so that high risk lambs could be treated more aggressively.     

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.     

Chronic copper toxicity in a dairy cow

A three year old Holstein dairy cow fed a ration containing a copper supplement died of chronic copper poisoning. The concentration of copper in the liver was 331 ppm (wet weight). The typical lesions of chronic copper toxicity including icterus, hepatic fibrosis and hemoglobinemic nephrosis were found at necropsy. The chronic copper toxicity was not considered to be a herd problem since the liver copper concentration in a slaughtered cull animal and blood samples taken from five animals in the same herd were within normal limits.     

家畜铜中毒研究进展

铜中毒是由于家畜摄食铜过多,或因肝细胞损伤,铜在肝脏等组织中大量蓄积,而突然释放进入血液循环所引起的一种重金属中毒性疾病。在生产中,家畜铜中毒屡见发生。文章归纳了铜中毒的发病特点和发病原因;总结了铜中毒的3 种发病机理,铜中毒的保护机制,铜与氧自由基的产生机制,铜毒理;论述了铜中毒的诊断依据、诊断指标和诊断方法;提出了铜中毒的综合性预防措施、治疗原则和治疗药物。为铜中毒病的诊断和防治提供了理论参考。     

Copper toxicity in ruminants: air pollution as a possible cause

Pathological findings and liver and kidney analyses confirmed that cattle had died of chronic copper poisoning on a farm in the north-eastern Transvaal. This is the first known published record of chronic copper intoxication of cattle in southern Africa. An epidemiological study revealed that a source of copper was air pollution which could have arisen from a nearby copper smelting unit. Buffalo and impala in an adjacent area of the Kruger National Park were found to have significantly higher liver copper levels than animals elsewhere in the Park. Prophylactic licks, containing zinc sulphate and sulphur, seemed to be successful in protecting cattle against the effects of the copper in the contaminated grazing.     

Copper toxicity in sheep: the effects of repeated intravenous injections of copper sulphate

Four Clun Forest, Suffolk cross sheep were given daily intravenous injections of copper sulphate. Three similar sheep acted as controls. The copper dosed sheep developed haemolysis and showed liver, kidney and brain damage similar to that seen in chronic copper poisoning. All animals survived for 30 days and two would have lived longer. Reticulocytes were produced after four days and continued to be produced, sometimes in high number throughout the course of the experiment.     

长期高铜暴露通过影响线粒体自噬和细胞焦亡诱导大鼠肝组织损伤

旨在探索高铜对大鼠肝组织损伤的作用机制。试验选取120只SD大鼠随机分为对照组、高铜I组、高铜II组、高铜III组和高铜IV组,分别连续每天按体重灌胃0、20、40、80、160 mg·kg^-1铜63 d,采集肝组织。使用ICP-MS测定肝组织铜含量,病理切片观察肝组织病理变化,透射电镜观察线粒体形态和线粒体自噬小体,RT-qPCR和Western blot检测肝组织NLRP3、Caspase-1、GSDMD、IL-1β、IL-18、Pink1、Parkin、LCB3、p62的mRNA和蛋白表达水平。结果显示,随着灌胃铜水平的增加,蓄积在肝组织中的铜含量呈剂量依赖性增加,且长期高水平铜暴露会造成明显的肝组织结构破坏;随着铜暴露水平的增加,线粒体自噬和细胞焦亡水平呈先上升后下降趋势;与对照组相比,高铜Ⅱ组、Ⅲ组中PINK1和LC3II/LC3I的mRNA和蛋白表达水平显著上升(P＜0.05),高铜Ⅱ组中p62的mRNA和蛋白表达水平显著降低(P＜0.05),高铜Ⅲ组NLRP3、Caspase-1、GSDMD、IL-1β的mRNA和蛋白表达水平显著上升(P＜0.05),高铜IV组表现为下调。高铜长期暴露可通过影响线粒体自噬和细胞焦亡诱导大鼠肝组织损伤。     

Copper Toxicosis in Bedlington Terriers

Copper toxicosis of Bedlington Terriers (Chronic progressive hepatitis) is a genetically transmitted disease. The typical feature of this disease is accumulation of copper in the liver tissue. The changes vary from mild hepatitis to chronic progressive hepatitis and cirrhosis.The material of this study consists of 2 cases of copper toxicosis examined at the Department of Pathology in Helsinki in the years 1980–82. Moreover a re-examination of tissue samples was made of all Bedlington Terriers examined during the years 1969–1982 at the same department. Six of the 14 examined dogs showed a positive reaction for copper in their liver tissues. The possible relationship of the examined dogs is not yet known.     

Pyrrolizidine alkaloids and seneciosis in farm animals. part 1: occurrence, chemistry and toxicology

Pyrrolizidine alkaloids belong to a class of phytotoxins which are present in more than 6000 plant species. The disease seneciosis in farm animals represents the severe poisoning by pyrrolizidine alkaloids from plants of the genus Senecio. This form of poisoning has been known since the end of the 19th century in Germany, the USA, Canada and New Zealand, and is mainly caused by Senecio jacobaea and related Senecio spp. in farm animals, including poultry. Animal poisoning by pyrrolizidine alkaloids is of worldwide importance. In Germany poisoning of horses and cattle by Senecio jacobaea, which was earlier named Schweinsberg disease, is of renewed relevance for veterinary medicine. The disease occurs almost entirely as a consequence of chronic poisoning and in general ends fatally. The ultimate cause is the formation of toxic metabolites of pyrrolizidine alkaloids in the liver, and their covalent binding to nucleic acids and proteins leading to liver cirrhosis. Because many pyrrolizidine alkaloids possess mutagenic, and a few also carcinogenic properties, European and international authorities are concerned about possible residue levels in food of animal origin. The review addresses in its first part several aspects, being the occurrence, the chemistry, and the toxicology of pyrrolizidine alkaloids as well as animal intoxications by poisonous plants. In the second part (46) clinical characteristics of animal seneciosis, the therapeutic interventions, the significant species differences and a critical assessment of so-called nontoxic amounts of Senecio plants in animal fodder with reference to cumulative lethal toxin doses are presented.     

Effects of Daily Oral Administration of Copper to Goats

Three goats were dosed orally with a 0.2 % aqueous copper sulphate solution. The dosing was 20 mg copper sulphate/kg body weight twice a day for 56 to 113 days. One of the goats accumulated substantial amounts of copper in the liver and developed two haemolytic crises. The two other goats showed only increased liver copper concentrations before they were killed. The results indicate that the goats were susceptible in varying degrees to repeated oral copper dosing, and that two of the goats were significantly less susceptible to copper than sheep. The goat that turned into a haemolytic crisis showed changes similar to those seen in sheep as far as blood and plasma parameters are concerned. The gross and histological lesions were also mainly of the same type as described in sheep. The hepatic lesions found in the goat differed to some degree from those found in sheep as the necroses were more distinctly located to the centrilobular area, and as the iron pigments were mainly located in phagocytes in the hepatic sinusóides.     

The Distribution of Soluble Copper- and Zinc-Binding Proteins in Liver and Kidney of Chronic Copper-Poisoned Goats

The distribution of copper and zinc among the soluble proteins in the liver and kidney from chronic copper-poisoned goats was examined after gel filtration of the proteins. The concentrations of copper in the liver and kidney cortex from five experimentally copper-poisoned goats were: 550–810 µg/g liver and 190–420 µg/g kidney cortex (wet weight). In general the copper-binding proteins from, both the liver and kidney samples were separated into two different fractions with approximate molecular weights (m.w.) of > 65,000 and 10,000, respectively. From the liver samples, varying amounts of copper were eluted in a fourth fraction with m.w. < 2,000. In the majority of kidney samples the dominating copper-binding protein fraction was the high molecular weight fraction. Absolute amounts of copper recovered in the metallothionein-like protein fraction were nearly the samt for all samples investigated. The distribution of zinc-binding proteins in both liver and kidney samples was nearly the same. The high molecular weight fraction dominated, and no zinc was bound to metallothionein-like proteins.     

Attempted induction of chronic copper poisoning in boma confined impala

Induction of chronic copper poisoning in ten boma-confined impala was attempted in a randomized, single dose, parallel designed, titration study using five increasing oral doses, ranging between 125 mg/kg to 1000 mg/kg, of copper oxide needles. Two untreated impala were kept as controls. Impala (n = 1) from each treatment group were culled 52 d and 105 d after treatment and examined for tissue copper accumulation and signs of chronic copper poisoning. Despite the high doses of copper administered to the impala and liver copper concentrations above 150 ppm WM achieved in two animals, no clinical signs related to chronic copper poisoning were observed. Faecal copper concentrations indicated that the major portion of copper oxide particles was excreted in the faeces.