Copper: deficiency toxicity

Plant and Animal Nutrient. Copper is one of seven micronutrients that has been identified as essential to the proper growth of plants (87). Cereal crops are by far the most affected by copper deficiency (see Wheat and other cereal grains). Greenhouse studies have shown yield increases from 38% to over 500% for wheat, barley, and oats (88) using copper supplementation. A tenfold increase in the yield of oats was reported in France (89). Symptoms of copper deficiency vary depending on species, but often it is accompanied by withering or chlorosis in the leaves that is not ammenable to iron supplementation. In high concentrations, particularly in low pH sods, copper can be toxic to plants. 

Chromium has proved effective in counteracting the deleterious effects of cadmium in rats and of vanadium in chickens. High mortality rates and testicular atrophy occurred in rats subjected to an intraperitoneal injection of cadmium salts however, pretreatment with chromium ameliorated these effects (Stacey et al. 1983). The Cr-Cd relationship is not simple. In some cases, cadmium is known to suppress adverse effects induced in Chinese hamster (Cricetus spp.) ovary cells by Cr (Shimada et al. 1998). In southwestern Sweden, there was an 80% decline in chromium burdens in liver of the moose (Alces alces) between 1982 and 1992 from 0.21 to 0.07 mg Cr/kg FW (Frank et al. 1994). During this same period in this locale, moose experienced an unknown disease caused by a secondary copper deficiency due to elevated molybdenum levels as well as chromium deficiency and trace element imbalance (Frank et al. 1994). In chickens (Gallus sp.), 10 mg/kg of dietary chromium counteracted adverse effects on albumin metabolism and egg shell quality induced by 10 mg/kg of vanadium salts (Jensen and Maurice 1980). Additional research on the beneficial aspects of chromium in living resources appears warranted, especially where the organism is subjected to complex mixtures containing chromium and other potentially toxic heavy metals. 

Two inherited human diseases that represent abnormal copper metabolism are Menkes syndrome and Wilson s disease. Menkes syndrome, with symptoms similar to those of copper deficiency, is characterized by a progressive brain disease, abnormally low copper concentrations in liver and other tissues, and diminished ability to transfer copper across the absorptive cells of the intestinal mucosa (USEPA 1980 Aaseth and Norseth 1986). Wilson s disease (hepatolenticular degeneration) is the only significant example of copper toxicity in humans. Wilson s disease is an autosomal recessive disorder that affects normal copper homeostasis and is characterized by excessive... 

C. A. Owen, Copper Deficiency and Toxicity Acquired and Inherited in Plants, Animals and Man , Noyes, Park Ridge, NJ, 1981. 

The effects nf copper deficiency in plants are varied and include die-back. inability to produce seed, chlorosis, and reduced photosynlhetic activity. In contrast, excesses of copper in the soil are toxic, as in the application of soluble copper salts to foliage. Fur this reason, copper fungicides are formulated with a relatively insoluble copper compound. Their toxicity to fungi ttrises from Lhe fact tltal (he latter produce compounds, primarily hydroxy and amino acids, which can dissolve the copper compounds from lhe fungicide. 

It is not easy to set a definite limit, in terms of the copper concentration in the diet, that will permit accurate predictions of the danger of copper deficiency or of copper toxicity in cattle and sheep. In particular, if the molybdenum concentration in the forage is high, extra amounts of copper are needed 10 prevent deficiency. Also, higher copper levels can be tolerated without danger of toxicity with molybdenum present. 

Monugasiric animals, including humans, are less sensitive than ruminants to either copper deficiency or toxicity. Copper deficiency in people has been round only when other complications, such as excessive bleeding, general starvation, and iron deficiency, arc also present. Wilson s disease, an inherited disease ol humans, prevents the loss of excess copper tram the body and brings on copper toxicity. No direct relationships have been found between levels of avaitable copper in the soil and the copper status of humans. 

Zinc absorption is inhibited by most food and the elevated plasma level lasts only 5 h after a dose thus it is better given five or six times a day, 1 h before or after meals. Zinc acetate may be better tolerated than the sulfate salt. Brewer prefers 25 mg elemental zinc, administered as the acetate, five or six times a day.53 Zinc is relatively non-toxic as a drug. If more than 1 g zinc is ingested in a single dose, toxic symptoms such as abdominal pain, nausea, vomiting, fever, drowsiness and lethargy may occur. A more significant toxicity problem is zinc-induced copper deficiency which can be corrected with a supplement of 0.5 mg of copper as copper sulfate per day.53... 

Hair serves to eliminate toxic materials (e.g., lead) and metabolites from the body, and may be used to monitor environmental contamination. For example, copper deficiency is a cause of Menke s kinky hair syndrome protein deficiency leads to hair loss and discoloration. Hair keratin carries a strong negative charge and binds inorganic materials it becomes prone to... 

Interactions Overabundance of one trace element can interfere with the metabolic use of another element available at normal levels. For example, addition of large amounts of zinc to a diet interferes with (antagonizes) intestinal copper absorption, resulting in copper deficiency from a diet with adequate copper content. Copper deficiency can provoke iron deficiency and anaemia. Molybdenum deficiency in animals can be induced by co-administration of large amounts of the similar element tungsten. Iron deficiency can also increase retention of cadmium and lead, and selenium has been proposed to protect against cadmium and mercury toxicity. 

Zinc was known to produce copper deficiency in experimental animals. The first report of zinc treatment for Wilson disease was published in 1979. Zinc causes induction of metallothionein in the intestinal cells, which binds copper with high affinity and holds it with high affinity until the intestinal cells are sloughed off. Thus, zinc inhibits absorption of copper from the intestine and increases the fecal excretion of copper. Zinc also blocks the reabsorption of endogenously secreted copper from sahva and gastric juice. A major advantage of zinc treatment is its low toxicity. 

Molybdate is known to induce copper deficiency, ft was found that the administration of molybdenum compounds, particularly with added sulfate, impaired copper metabolism in ruminants. Tetrathiomolybdate has been used to treat patients who were intolerant to D-penicillanune, trientine, and zinc. Tetrathiomolybdate seems to act both by blocking the intestinal absorption of copper and keeping it in a metabolically inert chelated form, which is not taken up by the liver. However, it induces only a modest cupriuresis. There are also known toxic effects of tetrathiomolybdate on the skeletal system of growing animals. Thus one should be extremely careful in administering this compound. It should be considered as an experimental drug. 

In general, molybdenum and its compounds are considered to be of low toxicity to humans however, molybdenum dust and fumes can cause irritation of the eyes, nose, throat, and respiratory tract. The trioxide and ammonium molybdate are more toxic than the ore molybdenite, the metal or the dioxide. It is not irritating to the skin, and is not a sensitizer. Mild cases of molybdenosis may be clinically identifiable only by biochemical changes (e.g., increases in uric acid levels due to the role of molybdenum in the enzyme xanthine oxidase). Excessive intake of molybdenum causes a physiological copper deficiency, and conversely, in cases of inadequate dietary intake of copper, molybdenum toxicity may occur at lower exposure levels. 

Data concerning the toxicity of the four discussed toxic minerals are presented in Tables 4.5 and 4.6. The uptake of elements is not entirely independent of one another. Elements of similar chemical properties tend to be taken up together. Sometimes one element has an inhibiting effect on another, or there can be a synergistic effect, e.g., enhancement of absorption of calcium in the presence of adequate amounts of phosphorus, or cadmium and lead hindering calcium and iron absorption, or zinc and copper antagonism and their influence on the ratio of Zn/Cu on copper deficiency. 

Williams, D.M., Clinical significance of copper deficiency and toxicity in the world population, in Clinical Biochemical and Nutritional Aspects of Trace Elements, Vol. 6., Prasad, A.S., Ed., Alan R. Liss, Inc., New York, 1982, p. 277. 

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