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Effect of dietary zinc on whole body surface loss of zinc: impact on estimation of zinc retention by balance method.

Whole-body sweat losses of zinc were studied in men during three separate studies on the effects of marginal intake of zinc. Zinc lost via the sweat appeared to be directly related to dietary zinc intake. Whole body zinc losses of an average of 0.49 mg/day were observed in the men during the control period when zinc intakes averaged 8.3 mg/day. On the other hand, when zinc intakes were 3.6 mg/day, whole body surface zinc losses were substantially lower, averaging 0.24 mg/day in two of the studies and slightly lower than control values in the third study. A loss of 0.62 mg of zinc/day was observed when 33.7 mg of zinc was fed. These losses reduced apparent balances by 12 to 84% and need to be considered when evaluating zinc retention. When men were eating the diets with marginal levels of zinc (3.6 mg/day), zinc losses in sweat gradually declined with time. This suggested a homeostatic mechanism to conserve zinc during periods of depletion.

Adult↗

Tissue zinc levels and zinc excretion during experimental zinc depletion in young men.

Six healthy young men participated in a confined zinc depletion-repletion study which lasted 10 to 11 wk. The depletion period varied from 4 to 9 wk during which the subjects consumed a semipurified formula diet supplying 0.28 mg zinc/day. During a 1-wk initial baseline period, 15.7 mg of zinc as ZnSO4 were fed; 6.0, 23.2, or 46.3 mg of zinc were given during a brief repletion period for three of the men. Plasma, whole blood, urinary, fecal, and seminal zinc decreased significantly by the end of the depletion period. Erythrocyte, saliva, and hair zinc did not change. Plasma and urinary zinc levels were highly correlated when urinary zinc was 150 micrograms/day or more. In five of six subjects a drop in urinary zinc to below 150 micrograms/day was noted before a decrease in plasma zinc to less than 70 micrograms/100 g, indicating that urinary zinc responds more rapidly than plasma zinc to dietary changes and may be useful for evaluating zinc nutriture. The endogenous zinc loss averaged 2.2 mg/day; addition of the loss occasioned by one seminal emission would bring the total to 2.8 mg/day.

Adult↗

Tissue zinc and copper levels in diabetic C57BL/KsJ (db/db) mice fed a zinc-deficient diet: lack of evidence for specific depletion of tissue zinc stores.

We investigated whether the decreased femur zinc concentrations reported in genetically obese diabetic db/db C57BL/KsJ mice reflected an increased propensity to zinc deficiency by determining zinc concentrations in tissues from 18-19-wk-old db/db and control mice following ad libitum feeding of a zinc-deficient diet (2 mg/kg) or restricted or ad libitum feeding of a zinc-adequate diet (20 mg/kg) for 12 wk. Although hepatic and renal zinc concentrations of db/db mice fed the zinc-deficient diet tended to be lower than in any other experimental group when expressed on a dry weight basis, zinc concentrations in these tissues were either not different from or greater than those of their nondiabetic controls when expressed on an ash weight basis, i.e., relative to all mineral constituents of these organs. Hepatic and renal copper concentrations of the diabetic db/db mice were either not different from or greater than those of their controls on an ash weight basis. Femur zinc concentrations of diabetic db/db mice fed zinc-adequate diets were lower than those of their controls on a dry weight basis but were not different from their controls on an ash weight basis. We found proportionately lower dry zinc, calcium and magnesium concentrations in femurs of the db/db mice fed a nonpurified diet than in femurs of their db/m and m/m controls. These findings suggest that the low femur zinc concentration reported in the diabetic db/db mouse probably reflects a generalized decrease in bone mineral content rather than a specific depletion of tissue zinc stores.

Animals↗

The zrfA and zrfB genes of Aspergillus fumigatus encode the zinc transporter proteins of a zinc uptake system induced in an acid, zinc-depleted environment.

Zinc is an essential micronutrient that cells must obtain from the environment in order to develop their normal growth. Previous work performed at our laboratory showed that the synthesis of immunodominant antigens from Aspergillus spp., including A. fumigatus, was up-regulated by a low environmental concentration of zinc. These results suggested that a tightly regulated system for the fungus to grow under zinc-limiting conditions must underlie the ability of A. fumigatus to acquire zinc in such environments. In this work, we show that zrfA and zrfB are two of the genes that encode membrane zinc transporters from A. fumigatus in this system. Expression of these genes is differentially down-regulated by increasing concentrations of zinc in the medium. Thus, the transcription of zrfB is turned off at a concentration 50-fold higher than that for zrfA transcription. In addition, phenotypic analyses of single zrfADelta and zrfBDelta mutants and a double zrfAzrfBDelta mutant revealed that the deletion of zrfB causes a greater defect in growth than the single deletion of zrfA. Deletion of both genes has a dramatic effect on growth under acid, zinc-limiting conditions. Interestingly, in neutral or slightly alkaline zinc-depleted medium, the transcriptional expression of both genes is down-regulated to such an extent that even in the absence of a supplement of zinc, the expression of zrfA and zrfB is strongly reduced. This fact correlates with the growth observed in alkaline medium, in which even a zrfAzrfBDelta double mutant was able to grow in a similar way to the wild-type under extremely zinc-limiting conditions. In sum, the zinc transport proteins encoded by zrfA and zrfB are members of a zinc uptake system of A. fumigatus that operates mainly under acid, zinc-limiting conditions.

Aspergillus fumigatus↗

The effect of ethanol feeding on zinc balance and tissue zinc levels in rats maintained on zinc-deficient diets.

We have studied tissue zinc levels and zinc balance in isocalorically pair-fed weanling rats on ZD liquid diets (0.9 microgram of zinc per milliliter of diet). Tissues were analyzed for zinc levels at weekly intervals while the animals were on the diets. The experimental animals were fed a ZDE diet, whereas sucrose was isocalorically substituted for alcohol in the pair-fed controls. After 1 week on ethanol feeding, the zinc content (microgram/gm wet weight) of the testes of the ethanol-fed rats was significantly lower than of the controls (p less than 0.001). After 2 weeks of ethanol, ethanol-fed animals also showed significantly lower zinc content in liver, hair, spleen, and kidneys (p less than 0.02) than their pair-fed controls. The zinc levels of the experimental animals in all tissues after 3 and 4 weeks of ethanol feeding were significantly lower (p less than 0.001) than that of the pair-fed controls with the exception of bone. Urinary and fecal zinc excretions of the ethanol-fed rats were significantly higher than that of the controls. Cumulative mean +/- S.D. fecal zinc excretions (microgram/28 days) were 1557 +/- 160 among the ethanol-fed animals vs. 730 +/- 150 among controls, p less than 0.01. Ethanol resulted in a mean negative zinc balance of 520 micrograms over 28 days, whereas controls showed a positive cumulative zinc balance of 300 micrograms. Thus ethanol ingestion resulted in negative zinc balance and decreased zinc concentrations of most tissues as compared to pair-fed controls.

Alcoholism↗

The effects of a dietary zinc supplement during lactation on longitudinal changes in maternal zinc status and milk zinc concentrations.

Dietary zinc intakes, selected biochemical indices of zinc status, and milk zinc concentrations were determined at monthly intervals throughout lactation for 53 middle-income lactating women, 14 of whom received a daily supplement of 15 mg zinc. Overall mean dietary zinc intake for the non-supplemented group (NZS) was 10.7 +/- 4.1 mg/day (mean +/- SD). The mean dietary zinc intake of the zinc supplemented group (ZS) was 12.2 +/- 3.5 mg/day, with an additional 12.8 +/- 1.5 mg/day from the supplement. For the NZS group, the highest mean plasma zinc concentration of 79 +/- 10 mu/dl, which occurred at month 4, was significantly less than the mean for non-lactating control women (86 +/- 10 micrograms/dl). ZS plasma zinc levels had a pattern similar to that of the NZS group for months 1-7. The rate of decline in milk zinc during lactation was significantly less for the ZS group compared to that of the NZS group (p = 0.02). It is concluded that milk zinc concentrations are influenced by maternal zinc intake within a physiological range and that the effects of low maternal intakes are most apparent with prolonged lactation.

Adult↗

Effectiveness of a zinc amino acid chelate and zinc sulfate in restoring serum and soft tissue zinc concentrations when fed to zinc-depleted pigs.

In a 36-d experiment, 32 pigs were depleted of Zn (24 d) using a soy-isolate (basal) diet (17 mg/kg of Zn) and then fed the basal diet (12 d) supplemented with 45 mg/kg of Zn from ZnSO4 (purified zinc sulfate dry powder, ZnSO4.nH2O) or from a Zn amino acid chelate (ZnAAC) to study the effectiveness of these dietary Zn sources in restoring serum and soft tissue Zn concentrations. Concurrently, nondepleted pigs were pair-fed both Zn-supplemented diets (eight pigs per diet) throughout the experiment. Serum Zn concentrations and serum alkaline phosphatase (ALP) activity of pigs fed the diets with no supplemental Zn were lower (P < .05) than those of nondepleted pigs after 7 and 14 d, respectively. After 24 d, concentrations of Zn in liver, pancreas, kidney, brain, and small intestine of Zn-depleted pigs were lower (P < .01) than those of nondepleted pigs. Except for decreased (P < .001) kidney Cu, soft tissue Cu and Fe concentrations were not affected by Zn status or Zn source. From d 24 to 36 (Zn repletion), serum and tissue Zn concentrations and serum ALP activities increased (P < .05), but the response was similar for both Zn sources in Zn-depleted and nondepleted pigs. At d 30 and 36, kidney Cu was increased (P < .01) in Zn-depleted pigs fed 45 mg/kg of Zn as either ZnSO4 or ZnAAC. Furthermore, Fe concentration was higher (P < .05) in intestinal segments of Zn-depleted and nondepleted pigs fed ZnAAC than in pigs fed ZnSO4. Accumulations of Cu in the kidney and Fe in the small intestine were affected by depletion and repletion of Zn and by dietary Zn source, respectively. In conclusion, serum and soft tissue Zn concentrations were clearly affected by Zn status: however, an effect of Zn source was not observed.

Alkaline Phosphatase↗

Influence of parenteral zinc and actinomycin D on tissue zinc uptake and the synthesis of a zinc - binding protein.

Parenterally administered zinc markedly increased the incorporation of 14-C-cystine and 65-Zn into a low molecular weight zinc binding protein (ZnBP) isolated from liver cytoplasm of rats fed an adequate amount of zinc. This zinc load significantly increased the zinc content in the liver. The increase in hepatic zinc content was inhibited by actinomycin D indicating that DNA-dependent RNA synthesis is required for zinc uptake into liver. Antinomycin D also produced a concomitant decrease in ZnBP synthesis indicating that this protein may be involved in the uptake mechanism in cells. Zinc repletion also stimulated the synthesis of hepatic ZnBP in zinc deficient rats. This stimulation was also prevented by prior administration of actinomycin D. A similar effect was observed in the intestinal mucosal cells. The data collectively indicate that the control of the synthesis of ZnBP which occurs at the transcriptional level of protein synthesis is responsive to zinc status and thus may have a function in zinc metabolism.

Animals↗

Intracellular distribution of zinc and zinc-65 in calves receiving high but nontoxic amounts of zinc.

The zinc homeostatic control breakdown in cattle fed a high but nontoxic amount of zinc was investigated. Liver copper was decreased by the 600 ppm added dietary zinc indicating altered copper metabolism. However, duodenal copper, liver and duodenal iron and manganese were not affected. Zinc-65 in blood was reduced 90% by the high dietary zinc 48 h following oral zinc-65 dosing. The 600 ppm supplemental zinc increased zinc by 500% in liver, 20 times in pancreas and kidney, and 100% in the duodenum. The increased liver and duodenal zinc was confined largely to the soluble cell fraction. This concentrating of excess tissue zinc in the soluble fraction may be an adaptive mechanism which detoxifies large quantities of zinc and prevents disruption of normal cellular activity.

Animals↗

Bioavailability of zinc from cooked philippine milled, undermilled, and brown rice, as assessed in rats by using growth, bone zinc, and zinc-65 retention.

The nutritional bioavailability of zinc from cooked milled, undermilled, and brown Philippine rice (variety PSB Rc14) was evaluated in rats, comparing results based on weight gain, tibia zinc incorporation (slope ratio analyses), and zinc radiotracer retention. Milling reduced the phytic acid and mineral content of the rice, resulting in zinc concentrations of 16.5, 19.4, and 27.2 microg/g and phytate/zinc molar ratios of 4, 20, and 28 for milled, undermilled, and brown rice, respectively. Measured zinc bioavailability was similar whether using growth, bone zinc, or radioisotope retention as criteria, at approximately 92, 86, and 77% of zinc sulfate, for milled, undermilled, and brown rice, respectively. However, the higher percent bioavailability of the zinc after milling was insufficient to compensate for the lower zinc content. With respect to zinc, the nutritional value was inversely related to milling, providing approximately 15, 17, and 21 microg bioavailable zinc/g rice, respectively, for milled, undermilled and brown rice of this variety.

Animals↗

Hydrolytic reaction by zinc finger mutant peptides: successful redesign of structural zinc sites into catalytic zinc sites.

To redesign a metal site originally required for the stabilization of a folded protein structure into a functional metal site, we constructed a series of zinc finger mutant peptides such as zf(CCHG) and zf(GCHH), in which one zinc-coordinating residue is substituted into a noncoordinating one. The mutant peptides having water bound to the zinc ion catalyzed the hydrolysis of 4-nitrophenyl acetate as well as the enantioselective hydrolysis of amino acid esters. All the zinc complexes of the mutant peptides showed hydrolytic activity, depending on their peptide sequences. In contrast, the zinc complex of the wild-type, zf(CCHH), and zinc ion alone exhibited no hydrolytic ability. These results clearly indicate that the catalytic abilities are predominantly attributed to the zinc center in the zinc complexes of the mutant peptides. Kinetic studies of the mutant peptides demonstrated that the catalytic hydrolysis is affected by the electron-donating ability of the protein ligands and the coordination environment. In addition, the pH dependence of the hydrolysis strongly suggests that the zinc-coordinated hydroxide ion participates the catalytic reaction. This report is the first successful study of catalytically active zinc finger peptides.

Amino Acid Sequence↗

The effect of growth hormone treatment alone or growth hormone with supplemental zinc on growth rate, serum, and urine zinc and copper concentrations and hair zinc concentration in patients with growth hormone deficiency.

Previous studies suggest that growth hormone (GH) may increase daily zinc requirements to meet the demand of growing bone and to replace increased urinary losses. We tested the hypothesis that zinc or copper availability might be limiting factors in the response of children receiving GH replacement. Ten patients with GH deficiency were followed for GH-induced changes in urine and serum zinc and copper during acute (0.3 IU/kg/day X 5 days) and chronic GH treatment (0.1 IU/kg/tiw). Zinc was measured in hair collected every 3 months. Zinc sulfate (220 mg/day) was given to half the patients during the second year of treatment. There was no evidence of zinc or copper deficiency, and zinc supplements did not venhance growth response to GH during the second year of treatment. We conclude that GH treatment in children does not alter serum or urine zinc or copper or hair zinc, and zinc supplementation does not improve growth in children with GH deficiency.

Adolescent↗

Zinc concentration of liver and kidneys from rat pups nursing dams fed supplemented zinc dipicolinate or zinc acetate.

The zinc concentration of liver and kidneys was determined in rat pups nursing dams given 10 micrograms Zn/ml as either zinc dipicolinate or zinc acetate in water solution during the last week of gestation and for 5 days of lactation. Dams were fed a casein-based diet that contained 8.5 micrograms Zn/g and 2.0 micrograms pyridoxine-HCl/g during this period. The zinc concentrations of both liver and kidneys from the 5-day-old pups nursing dams fed the zinc dipicolinate solution were significantly greater than the zinc concentrations of these tissues from pups nursing dams given a solution of zinc acetate. The results demonstrate that a greater quantity of dietary zinc is transferred from the intestine of the lactating female rat to the pups when zinc is fed in the form of zinc dipicolinate.

Acetates↗

Zinc and zinc ligands in human seminal plasma. II. Contribution by ligands of different origin to the zinc binding properties of human seminal plasma.

The zinc binding properties of whole human seminal plasma and various fractions of split ejaculates were analysed with gel chromatographic and dialysis methods. The proportion of dialyzable zinc was strongly correlated to the zinc/fructose ratio in the seminal plasma, i.e. correlated to the relative contributions by the prostate and seminal vesicles, respectively. Zinc originates, however, almost entirely from the prostate gland. The non-diffusible zinc ligands thus seemed to originate from the seminal vesicles. This could also be confirmed in experiments with split ejaculates. The high molecular weight (HMW) zinc ligands from the seminal vesicles have also a higher affinity for zinc than the low molecular weight (LMW) ligands from the prostate. A redistribution of zinc therefore takes place after ejaculation. The HMW zinc ligands from the seminal vesicles were found to have an isoelectric point at 6.1-6.7, to be glucoproteins, and to have an apparent molecular weight of 250,000. The possible physiological implications of a redistribution of zinc after the ejaculation is discussed in view of the fact that zinc is of importance for many functional properties of the human spermatozoa.

Adult↗

Geophagia in Turkey: iron and zinc deficiency, iron and zinc absorption studies and response to treatment with zinc in geophagia cases.

A brief summary of the research carried out on the problem of geophagia is reported in this paper. Geophagia was a common finding among Turkish children and women in villages, associated with severe iron deficiency anemia in addition to zinc depletion. The syndrome characterized by geophagia, iron deficiency anemia, growth retardation, hypogonadism and zinc deficiency has been observed in both sexes in Turkey for several decades. Zinc deficiency has been also shown by our group in this syndrome. The decreased concentrations of zinc in serum, plasma, RBC, hair and urine were measured by atomic absorption spectrophotometer. Oral iron (both inorganic and radioactive iron) and zinc absorption tests were carried out with and without clay and revealed decreased iron and zinc absorption in some cases with prolonged geophagia. Therefore, malabsorption of iron and zinc was considered to be an additional and/or a new finding in the syndrome. Furthermore, Turkish clay most probably inhibits zinc absorption in a way similar to its inhibition of iron absorption. It was worthy of observation that some Turkish patients with this syndrome had a thalassemia-like appearance with similar skull-bone changes. Finally, growth retardation and delayed puberty were shown to be corrected by oral zinc treatment for 6-month terms. Linear growth and sexual maturation were found to be greater in the zinc-treated group than in the controls.

Adolescent↗

Relationship between soil zinc, dietary zinc and zinc nutritional status of humans.

The effect of consumption of the staple food grown in soil zinc deficient area on zinc nutritional status of human beings was investigated. One village each from an area which has been classified under >75%, 25-50% and 50-75% soil zinc deficiency was selected for the study from Andhra Pradesh. Thirty families from each village were selected and the zinc content of soil, rice (grown in that soil) and serum (of people consuming the same rice) of the selected subjects was estimated. Food and nutrient intake of the respondents were calculated by using diet survey. Heights and weights of children of selected families were taken to assess the relationship between soil zinc levels and growth. Results show that the soil zinc deficiency has an impact on the zinc levels of rice grown in the same soil. However, serum zinc levels of adults and growth of children seem to be influenced by protein content and source of protein in the diet in addition to zinc levels of the diet.

Adolescent↗

Homeostatic control of zinc metabolism in men: zinc excretion and balance in men fed diets low in zinc.

Zinc metabolism was studied in 11 men. The study began with 28-d equilibration when dietary zinc was 159 mumol/d (X), followed by 35-d periods when the diet contained 21.9 (I), 37.5 (II), 51.6 (III), or 67.8 (IV) mumol Zn/d in random order, and ended with 35 d with X. The diet was conventional foods and egg white protein. Zinc balance, including surface and semen losses, was zero only during I. Semen zinc was unaffected by diet. Plasma zinc dropped to 0.44 and 0.49 mumol/L in two subjects during I and was significantly decreased during I compared with X (P < 0.0002). Urinary zinc declined with decreasing zinc intake. A combination of urinary and plasma zinc criteria from Baer and King (Am J Clin Nutr 1984; 39:556-70) could be used to distinguish stages of zinc deficiency. By these criteria, no subjects were deficient during IV, one was marginally deficient during III, three were marginally deficient during II, and seven were deficient during I.

Adult↗

Interaction of zinc and vitamin A in rats receiving a regional diet of Manaus, Amazonas, Brazil. Effect of supplementation with vitamin A, zinc and zinc and vitamin A.

The interaction of zinc and vitamin A in rats receiving a regional diet of Manaus, supplemented with vitamin A, zinc and zinc and vitamin A was studied. The regional diet was elaborated according to data of Shrimpton and Giugliano (6), for families receiving less than two minimum salaries. The biological test to study the interaction was based on the depletion of zinc and vitamin A in rats in the period of lactation, and a period of repletion where supplements of zinc (0.82 mg%) and vitamin A (94.2 micrograms %) were given, either separately or together, according to the recommendations of the Committee on Laboratory Animal Diets (7). From the results, it was concluded that there was an interaction of these nutrients in terms of mobilization of hepatic vitamin A. Although the regional diet of Manaus did not meet the zinc RDA, the amount present was enough to utilize the available vitamin A. Although the amount of zinc present in the diet, as determined by parameters of bioavilability, such as growth, concentration in organs and zinc-dependent enzymes, was adequately used by the animals, probably due to promoting factors in the diet. The Manaus regional diet needs to be supplemented with vitamin A in order to maintain the hepatic reserves, and with zinc, to maintain the normal levels of vitamin A in plasma.

Animals↗