Copper deficiency, zinc effect

For patients who are unable to tolerate penicillamine, trientine, another chelating agent, may be used in a daily dose of 1-1.5 g. Trientine appears to have few adverse effects other than mild anemia due to iron deficiency in a few patients. Zinc acetate administered orally increases the fecal excretion of copper and is sometimes used for maintenance therapy. The dose is 50 mg three times a day. Zinc sulfate (200 mg/d orally) has also been used to decrease copper absorption. Zinc blocks copper absorption from the gastrointestinal tract by induction of intestinal cell metallothionein. Its main advantage is its low toxicity compared with that of other anticopper agents, although it may cause gastric irritation when introduced. 

Subsequent studies have given some insight into the cellular mechanisms of the copper zinc interaction. Evans al. (29) found the 1000 1 Zn/Cu ration inhibited 64Cu uptake only in zinc-deficient rats, and that its effect was not on uptake from the lumen, but rather on transfer to the body. Parenteral injection of copper prior to luminal dosing with 65Zn also reduced net copper absorption (32) (Fig 3) but again, this was due to reduced transfer of copper across and out of the mucosal cell. Also, in the study of Van Campen (31) of the effect of excess copper on zinc absorption, indications of a predominant Influence within the mucosal cell were developed. 

Copper and Zinc in Aerobic Metabolism. Cytochrome oxidase, the terminal oxidase in the electron transport chain contains an atom of copper. On this enzyme the protons and electrons generated during oxidative metabolism combine with elemental oxygen to form water. During copper deficiency the tissue concentration of cytochrome oxidase is reduced. While the effects of lower cytochrome oxidase activity on exercise has not been described, it is likely that aerobic energy metabolism will be diminished. This effect of copper deficiency was first described in animals with myelin aplasls — the degeneration myelin (86). The oxidative process of phospholipid synthesis, a primary component of myelin, was depressed. Liver mitochondria had impaired respiratory activity (87). Cytochrome oxidase activity was also depressed in brain, heart and liver. 

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 patients with Wilson s disease, penicillamine is rapidly attached to copper and, although higher doses are used, taste disturbances develop in a lower frequency, about 4% (SED-8, 536). It has been suggested that dysgeusia is related to deficiency of copper or zinc, but a strong connection between taste impairment and urinary copper excretion has not been demonstrated (118). Serum copper concentrations remained within normal limits and copper supplements were not effective in prevention (119). 

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. 

F., Peu, P., Martinez, J., and Hinsinger, P. (2005). Bioavailability and exhactability of copper and zinc in a soil amended with pig slurry effect of iron deficiency in the rhizosphere of two grasses. In Biogeochemistiy of Trace Elements in the Rhizosphere, ed. Huang, P. M., and Gobran, G. R., Elsevier, Amsterdam, The Netherlands, 337-363. 

While absorption of the copper contained in foods of plant origin is seemingly efficient, it has been reported that rats fed on raw meat developed copper deficiency. This suggests that the copper present in raw meat is not avaliable for absorption. Experience in this direction is well summarized and the pertinent literature quoted in a recent article by Moore et al. (M29). Guggenheim (G16), on the other hand, presents recent evidence to the effect that the meat anemia in mice is due to the high zinc content of meat in the presence of low but, by itself, adequate amounts of copper, and that a concomitant lack of calcium further aggravates the situation. One must wait to see whether this applies to the raw meat copper deficiency of... 

Hammermtiller JD, Bray TM, Bettger WJ. Effect of zinc and copper deficiency on microsomal NADPH-dependent active oxygen generation in rat lung and liver. JNutr 1987 117 894-901. 

According to the investigations of Fattinger (1950), the fungicidal action of copper is enhanced by cadmium, cobalt, nickel and zinc compounds in Alternaria tenuis and Trichothecium roseum cultures. Zinc sulfate (ZnSO 7HjO) was tried in place of copper sulfate its effect however was inferior to that of the copper compound. Nevertheless, it is still used against rosette disease a physiological disease caused by zinc deficiency. 

Copper deficiency is extremely rare, and there is no evidence that copper ever need be added to a normal diet. Even in chnical states associated with hypocupremia (sprue, celiac disease, and nephrotic syndrome), effects of copper deficiency usually are not demonstrable. Anemia due to copper deficiency has been described in individuals who have undergone intestinal bypass surgery, in those who are receiving parenteral nutrition, in malnourished infants, and in patients ingesting excessive amounts of zinc. While an inherited disorder affecting copper transport (Menkes disease) is associated with reduced activity of several copper-dependent enzymes, this disease is not associated with hematological abnormalities. 

The toxic effects of cadmiun are further manifested by a negative action on the metabolism of iron, copper and zinc which results in a deficiency of these metals with relevant disturbances. Cadmium also exerts teratogenic, mutagenic and carcinogenic effects [10]. 

It must be stressed that self-medication or uncontrolled trial of zinc therapy are not advocated. The side effects of excess zinc dosage are not acute, at least at the levels proposed. Adverse metabolic effects include the induction of a secondary copper deficiency (Fischer et al., 1984). An impairment of laboratory indices of the immune response has been noted at a dosage of 300 mg Zn per day, over a 6-week period (Chandra, 1984). 

It may be noted that many toxic metals are also essential for the body, at trace levels. Their absence from the diet can produce various deficiency syndromes and adverse health effects. Such essential metals include selenium, copper, cobalt, zinc, and iron. On the other hand, excessive intake can produce serious adverse reactions. Also, a number of metals, such as aluminum, bismuth, lithium, gold, platinum, and thallium, have been used in medicine. Despite their beneficial effects, excessive intake of these metals and their salts can cause serious poisoning. 

Bioavailability and extractability of copper and zinc in a soil amended with pig slurry Effect of iron deficiency in the rhizosphere of two grasses... 

D. Unithiol increases the urinary excretion of copper and zinc, an effect that is not anticipated to be clinically significant in patients without preexisting deficiency of these trace elements. 

An increase in the incidence of fetal resorptions and decreased fetal weights were observed in rats after oral exposure to 200 mg zinc/kg/day prior to and during mating and throughout gestation (Schlicker and Cox 1968). Alopecia and hair discoloration were observed in the offspring of mice exposed to 260 mg zinc/kg/day (Mulhern et al. 1986). These effects are believed to be the result of zinc-induced copper deficiency. No developmental effects were observed in rats exposed to up to 100 mg zinc/kg/day (Schlicker and Cox 1968 Uriu-Hare et al. 1989). 

Anemia has been observed in humans and animals after oral exposure to zinc. It has been postulated that excess zinc intake may result in copper deficiency (mechanisms of action are discussed in Section 2.3.5). The anemia observed following zinc intake is believed to be caused by the copper deficiency. Administration of copper has been shown to be effective in increasing the hemoglobin levels (Porter et al. 1977 Smith and Larson 1946). 

Johnson MA, Flagg EW. 1986. Effects of sucrose and cornstarch on the development of copper deficiency in rats fed high levels of zinc. Nutr Res 6 1307-1319. 

L Abbe MR, Fischer PWF. 1984b. The effects of high dietary zinc and copper deficiency on the activity of copper-requiring metalloenzymes in the growing rat. J Nutr 114 813-822. 

D-Penicillamine 11.26) has a favourable chemotherapeutic effect on adenocarcinoma implanted into rats. This is attributed to inactivation of the superoxide dismutase that is controlled by copper and zinc, a loss for which normal cells are compensated by the manganese-controlled analogous enzyme in which cancer cells are deficient (Okuyama and Hitoshi, 1981 Oberley, 1982). 

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