Tissue zinc content

Various estimates have been made of the whole body content, based initially on direct cadaver analysis and more recently by isotope dilution techniques (Kennedy et al., 1978). Values between 1-2 g for an adult are quoted. Since the greatest amount of zinc is found inside cells, the average tissue concentration is higher than that found in body fluids. Zinc is present in all metabolically active tissue and some results obtained from tissue obtained at autopsy of accident victims, are shown in Table 5. These were obtained using neutron activation analysis (Smith, 1967) and by flame MS (Lyon et al., 1989, Martin et al., 1992). 

The needle biopsy makes a variety of tissues available for study. Liver, skeletal muscle, kidney and iliac crest bone can be obtained and have been used in research. Liver biopsy is the most widely used of these procedures since this is a large and fairly homogenous organ, and the technique is widely employed for the histopathological diagnosis of common liver disorders. 

Example of the Determination of Zinc in Uver Biopsies (Mills et al., 1983) 

The biopsies were taken with a Trucut needle from adjacent sites in the liver, using either a percutaneous method or under direct vision at laparotomy. Preliminary studies using autopsy liver had shown that this type of needle did not cause zinc contamination of the sample. 

The biopsy tissue was piaced into an airtight plastic envelope and frozen immediately. All samples were stored at -20°C and processed as a single batch. The wet weight was taken (average 25.5 mg), the sample dried at 100°C and the weight recorded, and then the dried material was ashed at 550°C in a muffle furnace. 

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Zinc treatments had no effect on overall egg production, feed conversion, feed consumption, hatchability, or progeny growth to age 3 weeks. Zinc was elevated in eggs from hens fed the 2000 mg/kg diet, but chick performance and tissue zinc content were unaffected by maternal zinc nutritional status (Stahl etal. 1990)... 

TISSUE ZINC CONTENT OF ACCIDENT VICTIMS (WEST OF SCOTLAND) Determined as mg/kg dry weight, by neutron activation analysis (Smith, 1967)... 

Segments of human aorta obtained fresh at autopsy were freed from blood and covering connective tissue and analyzed manometrically for carbonic anhydrase activity. Twelve specimens from 7 males and 5 females yielded nearly a 9-fold spread in values (0.12 to 1.05 units).31 This is interesting in view of the zinc content of carbonic anhydrase and the extremely wide variations in the zinc content of blood plasma and spleens which have been observed (pp. 55 and 72). 

One of the most interesting aspects of the changes in a-D-man-nosidase activity known to occur in vivo is the possible relationship with changes in zinc concentration in the tissues. In the case of rat epididymis, changes in enzyme activity have been monitored in parallel with measurements of zinc content.26 There was a positive correlation between the two variables, as both increased with age. The drop in a-D-mannosidase activity resulting from orchidectomy was accompanied by a 4-fold fall in the zinc content of epididymis, but the restoration of enzyme activity produced by subsequent injection of testosterone was not reflected in a detectable rise in the proportion of zinc. 

In zinc-deficient rats, the zinc content of the epididymis was only about half the normal value,28,87 and the level of a-D-mannosidase activity was also little over half the value usually observed.26 However, the zinc concentration of the tissue was still in vast excess over that required for stoichiometric combination with the enzyme protein, calculated on any probable estimate of its specific activity and molecular weight (see Section III,5 p. 433). 

The average human ingests 10-15 mg of zinc a day.3 Although it is poorly absorbed, the concentrations of zinc in tissues are relatively high and the metal plays an essential role in a multitude of enzymes. The total zinc content of a 70-kg person is 1.4-2.3 g. A typical tissue concentration of Zn2+ is 0.3-0.5 mM an unusually high content of 15 mM is found in the prostate gland. 

Persistent acute body zinc loss has resulted in many symptoms in addition to taste and smell dysfunction if losses continue at significant levels for periods of 14 days or more. These symptoms Include mental confusion, cerebellar dysfunction, including intention tremor and ataxia, an erythrematous, Intracrural rash, buccal epithelial lesions and ulcers, and acute toxic psychosis (,6). The altered mental state of these patients can be related to the rapid depletion of the relatively high zinc content in the limbic system of the brain (16.17), demonstrating that zinc can cross the blood brain barrier bidirectionally, dependent upon the gradient, and that it can be readily mobilized from brain tissue. 

Definitions of Zinc Deficiency. It is clear that zinc deficiency can be defined only with difficulty since the zinc content of a single body fluid or tissue level cannot provide a definitive estimate of body zinc status (If3 ) It is also not possible to rely on the concentration of zinc in several body tissues to estimate body zinc status since differing concentrations in different tissues lead to non-definitive conclusions. 

Relative (zinc in cookie A=100%) biological value based on femur zinc content. Table VII. Tissue concentration and absorption of zinc in rats fed bread > ... 

In a preliminary experiment, weanling male Wistar rats were depleted of zinc by feeding a low zinc basal diet (0.6 yg/g zinc) for two weeks and then repleted by adding 12 yg/g zinc as zinc sulphate. The analysis of the zinc content of the different tissues at weekly intervals for four weeks revealed that the body weight and the total femur zinc were the parameters of choice because the responses were linear with duration of feeding. Moreover, the relative errors of the slopes of the regression lines were minimal (5). The results of this experiment also showed that since depletion did not reduce the variability in these parameters, it was not essential for the assay. 

It is estimated that the zinc content of a normal 70-kg male is approximately 1.5-2.0 gm. Liver, kidney, bone, retina, prostate, and muscle appear to be rich in zinc. In man, zinc content of testes and skin has not been determined accurately, although clinically it appears that these tissues are sensitive to zinc depletion. 

Enzyme Changes in Zinc Deficiency. Since zinc is required for many enzymes, it is reasonable to speculate that the level of zinc in cells controls the physiological processes through the formation and/or regulation of activity of zinc-dependent enzymes. Until 1965, there was no evidence in the literature to support this concept. During the past decade it has been shown that the activity of various zinc-dependent enzymes was reduced in the testes, bones, esophagus, and kidneys of zinc-deficient rats in comparison with their pair-fed controls (90,91,100,101), These results correlated with the decreased zinc content in the above tissues... 

Reduced activity of carbonic anhydrase, another zinc metalloenzyme, has been reported in gastric and intestinal tissues and in erythrocytes when the activity of the enzyme was expressed per unit of erythrocytes (91), Recently in sickle-cell-disease patients, an example of a conditioned zinc-deficient state, the content of carbonic anhydrase in the red cells was found to be decreased, correlating with the zinc content of the red cells (10,75). Inasmuch as the technique measured the apoenzyme content, it appears that zinc may have a specific eflFect on the synthesis of this protein by some mechanism yet to be understood. 

Blood Cell Zinc. Some investigators have suggested that the zinc content of white cells and platelets better reflects tissue zinc. The zinc content of neutrophils, lymphocytes, and platelets has been shown to decline more rapidly than plasma zinc in experimental studies of zinc depletion in humans. However, the relatively large volume of blood required and problems with contamination make large-scale application to patients in the hospital or to population surveys difficult, especially in studies involving children. 

Although trace element abnormalities occur in chronic renal failure, few symptoms have been attributed to them in nondialyzed patients. In dialysis patients these disturbances appear to be qualitatively similar but more severe (T7). They have been extensively reviewed by Alfrey (A5). Total body zinc (except in erythrocytes), strontium, aluminum, and tin are generally increased, whereas total body rubidium is decreased. Iron stores tend to be increased in the spleen and liver in dialyzed patients, especially after ferrous sulfate therapy. Copper is increased in lung tissue and decreased in heart tissue and erythrocytes. Molybdenum and cadmium are decreased in renal tissue but increased in liver tissue of dialyzed and nondialyzed patients. Total body zinc content is significantly increased (A5), but hypozincemia, frequently observed in dialysis patients, has been blamed for taste impairment and impotence and there is conflicting evidence on whether zinc repletion corrects these abnormalities (K4, Ml2). Nickel is also increased in the serum of uremic patients, but this does not appear to be associated with a corresponding increase in tissues (S5). It cannot be concluded that trace element retention in renal failure is of no clinical importance, as shown by the problem of aluminum intoxication, to be discussed later. In addition, trace elements such as rubidium and bromine, which are rapidly depleted in uremic patients on maintenance dialysis (A5), may prove to be essential in normal metabolism. Thus the clinical importance of these element alterations remains unclear. 

Table 3. Copper and zinc content of erythrocuprein isolated from human and bovine tissues. Data taken from a (64), b (69), c(72), d (74), e (82), f (55), and converted values using a molecular weight of 34,000 from g (66), h (58), i (87)...

The hair sample is digested as described above for tissue or food samples, and the zinc content determined by flame AAS. 

Table 4. Zinc content of sheep biological tissues...

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