Urinary zinc excretion and zinc status of patients with Β-thalassemia major

In this study, zinc status and urinary zinc excretion with and without desferrioxamine (DFO) infusion and the relationship between urinary zinc excretion and renal tubular dysfunction in thalassemia major (TM) patients were investigated. Forty TM patients were given four DFO infusions on alternate days over a 1-wk period prior to the transfusion. On each day that DFO was given, a 24-h urine collection initiated. DFO was omitted for 1-wk before the following transfusion and during the period four 24-h urine collections were performed. Twenty healthy children provided 24-h urine collection as controls. Blood samples were taken on each of two consecutive transfusion days of the patients and from the controls. Urinary zinc excretion was measured and plasma and red blood cell (RBC) zinc analysis were performed by inductively coupled plasma-atomic emission spectrophotometry. UrinaryN-acetyl-Β-D-glucosaminidase (NAG) activity and creatinine were determined in morning urine specimens. The mean plasma zinc concentration was significantly lower in the patients not given DFO compared to the values of the patients given DFO and the control group. The mean RBC zinc concentration (Μmol/g Hb) in the patients (with and without DFO) and the control group were similar. Urinary zinc excretion was significantly higher in the patients receiving DFO compared to the control group, whereas urinary zinc excretion in the patients not given DFO was not different from the controls. Urinary NAG indices (U/g Cr) were significantly higher in the patients compared to controls. Urinary zinc excretion was correlated with the urinary NAG indices.     

Serum zinc levels and Alzheimer’s disease

Concentrations of zinc in postmortem serum and four brain regions were measured by flame atomic absorption spectrometry and instrumental neutron activation analysis, respectively, in nine Alzheimer’s disease (AD) and eight control subjects. A statistically significant elevation of zinc serum was observed in AD subjects (136.4±66.8 μg/dL) compared with age-matched control subjects (71.1±35.0 μg/dL). No significant differences were observed between AD and control zinc concentrations in the amygdala, hippocampus, cerebellum, and superior and middle temporal gryi.     

Dietary phytate × calcium/zinc millimolar ratios and zinc nutriture in some Ontario preschool children

Millimolar ratios of phytate/Zn, Ca x phytate/Zn, and Ca x phytate/Zn per 4.2 MJ were calculated from 3-d weighed-food records collected from 62 male (M) (mean age: 58 +/- 7 mo [mean +/- SD]) and 44 female (F) (mean age: 58 +/- 6 mo) preschool children from Southern Ontario. Food-composition values for phytate were based on laboratory analysis and the literature. No gender differences existed for median millimolar ratios of phytate/Zn (median: M, 5.3; F, 5.3), and Ca x phytate/Zn per 4.2 MJ (M, 68.1; F, 59.5), but median intakes of phytate (M, 399; F, 333 mg/d) and median millimolar ratios of Ca x phytate/Zn (median: M, 102.1; F, 72.3; p less than 0.01) were higher for boys than for girls. Of the children, only two (1M, 1F) and 22 (17 M, 5F) had millimolar ratios of phytate/Zn and Ca x phytate/Zn per 4.2 MJ, respectively, that were above critical values. Millimolar ratios of Ca x phytate/Zn (p = 0.06) and Ca x phytate/Zn per 4.2 MJ (p = 0.05) were higher in boys with hair zinc less than 1.07 mumol/g v greater than or equal to 1.07 mumol/g. Analysis of variance showed that height was influenced by an interaction between millimolar ratios of Ca x phytate/Zn per 4.2 MJ and sex (p = 0.0007), when age and midparent height were treated as covariates. Results suggest that dietary Ca x phytate/Zn millimolar ratios, when expressed per 4.2 MJ, influenced the zinc nutriture of these Southern Ontario boys.     

Protection by zinc against UVA— and UVB-induced cellular and genomic damage in vivo and in vitro

For many years, zinc salts have been used both topically and orally to treat minor burns and abrasions as well as to enhance wound repair in man and animals. In this study we describe the protective effects of zinc against UV-induced genotoxicity in vitro and against sunburn cell formation in mouse skin in vivo. Cultured skin cells from neonatal mice showed a dramatic increase in the number of micronuclei as a result of UVA and UVB irradiation. Inclusion of zinc at 5 μg/mL in the medium significantly reduced the frequency of micronuclei and of micronucleated cells. In hairless mice, topical application of zinc chloride for 5 consecutive days or a single application 2 h prior to UV exposure reduced the number of sunburn cells in the epidermis as did application of zinc 1 h after exposure. Application 2 h after irradiation also tended to have a protective effect, although there was a large variation between animals. It is proposed that an influx of zinc can protect epidermal cells against some of the more delayed effects of UV-induced damage.     

A role for zinc in postsynaptic density asSAMbly and plasticity?

Chemical synapses are asymmetric cell junctions that mediate communication between neurons. Multidomain scaffolding proteins of the Shank family act as major organizing elements of the "postsynaptic density"--that is, the cytoskeletal protein matrix associated with the postsynaptic membrane. A recent study has shown that the C-terminal sterile alpha-motif or "SAM domain" of Shank3 (also known as ProSAP2) can form two-dimensional sheets of helical fibers. Assembly and packaging of these fibers are markedly enhanced by the presence of Zn2+ ions. Zn2+ can be released together with glutamate from synaptic vesicles and can enter the postsynaptic cell through specific ionotropic receptors. Based on these observations, we propose a new model of synaptic plasticity in which Zn2+ influx directly and instantly modulates the structure and function of the postsynaptic density.     

Strong and weak zinc binding sites in human zinc-α2-glycoprotein

Zinc-α2-glycoprotein (ZAG) is an adipokine with an MHC class I-like protein fold. Even though zinc causes ZAG to precipitate from plasma during protein purification, no zinc binding has been identified to date. Using mass spectrometry, we demonstrated that ZAG contains one strongly bound zinc ion, predicted to lie close to the α1 and α2 helical groove. UV, CD and fluorescence spectroscopies detected weak zinc binding to holo-ZAG, which can bind up to 15 zinc ions. Zinc binding to 11-(dansylamino) undecanoic acid was enhanced by holo-ZAG. Zinc binding may be important for ZAG binding to fatty acids and the β-adrenergic receptor.     

Are copper, zinc and selenium in erythrocytes valuable biological indexes of nutrition and pathology?

The real significance of the level of trace elements copper, zinc and selenium in erythrocytes is still a matter of debate. This review is an evaluation of the potential value of copper, zinc and selenium in red blood cells in physiology, nutrition and pathology, taking into account the other commonly used indices and the analytical difficulty encountered for erythrocyte determinations. The main analytical methods and reference values in erythrocytes are also presented. The literature of the last 3 decades was analyzed. On the basis of these papers, the role of erythrocyte copper in various pathologies should be re-investigated, especially when they include inflammatory processes or hormonal changes. The main interest of zinc determination in red blood cells concerns thyroid pathology. In general, the value of selenium in erythrocytes agrees with selenium in serum and its determination is often unnecessary.     

S-nitrosothiol and nitric oxide reactivity at β-diketiminato zinc thiolates

The β-diketiminato zinc halide [Me₂NN]ZnCl₂Li(THF)₃ (1) is prepared in 51% isolated yield by addition of the lithium β-diketiminate Li[Me₂NN] to ZnCl₂ in THF. Reaction of 1 with 2 equiv. of the thallium thiolate TlSCy provides {[Me₂NN]Zn(μ-SCy)₂Tl}₂ (2), a TlSCy adduct of [Me₂NN]ZnSCy, as colorless crystals in 51% yield. Reaction of 1 with 1 equiv. TlSR provides the dinuclear {[Me₂NN]Zn(μ-SR)}₂ (R = Cy (3), ^tBu (4)) which possess unsymmetrically bridging thiolate ligands with pairs of dissimilar Zn-S distances in the solid state (2.350(3) and 2.417(3) Å for 3; 2.312(1) and 2.415(1) Å for 4). Reaction of 1 with LiSCPh₃ results in the mononuclear zinc thiolates [Me₂NN]ZnSCPh₃(THF) (5) and [Me₂NN]ZnSCPh₃ (6) with shorter, but similar Zn-SR distances of 2.225(2) and 2.214(1) Å. Variable temperature ¹H NMR studies of 3 and 4 in CDCl₃ suggest that the aliphatic thiolates exist predominately as monomeric species in solution near room temperature, though at −50 °C two different β-diketiminato species are observed for 3. Thiolate exchange among 3, 4, and 6 also takes place on the NMR timescale near room temperature. Both 4 and 6 undergo transnitrosylation with CySNO in CDCl₃ to give {[Me₂NN]ZnSCy}₂ (3) and the corresponding S-nitrosothiol ^tBuSNO or Ph₃CSNO. Nitric oxide does not react with 4 or 6 under anaerobic conditions, but in the presence of O₂, NO cleaves the zinc-thiolate bond of 4 to rapidly give ^tBuSNO. Similarly, anaerobic NO₂ reacts with 4 to give ^tBuSNO providing insight into the active nitrogen oxide species capable of cleaving Zn-SR bonds.     

Serum zinc and its relation to bone mineral density in β-thalassemic adolescents

Trace elements have been considered to play critical roles in bone metabolism. This study aims at determining the serum zinc profile and its association with bone mineral density (BMD) abnormalities in thalassemic patients. In 131 transfusion-dependent β-thalassemic patients, aged 10–20 yr, serum levels of zinc were measured by flame atomic absorption spectrophotometry (F-AAS). BMD values at the lumbar (L1–L4) and femoral neck were determined by dual X-ray absorptiometry (DXA). Dietary zinc intake and daily consumption of calcium were evaluated by a food-frequency questionnaire. Low serum zinc was found in 84.8% (in 44.7% severely low). Below −2 BMD Z-scores were observed in 68.7% and 17.6% of the patients at the lumbar and femoral regions, respectively. Female patients with severe zinc deficiency had lower lumbar BMD Z-scores in comparison to the other females (−3.26 vs −2.54). Serum zinc in females with femoral BMD Z-scores <−2 was significantly lower by 16.4 μg/dL than other females. Our study suggests that serum levels of zinc can be lowered in the thalassemic patients and partly affect the BMD.     

Seminal plasma zinc concentration and α-glucosidase activity with respect to semen quality

This study was conducted to examine the relationship between the concentration of zinc and neutral α-glucosidase (NAG) with semen quality. Semen samples from 75 male partners of couples who were attending the Obstetrics and Gynecology Department were analyzed for semen quality. Based on sperm count, the subjects were divided into three groups. Zinc and neutral α-glucosidase activity were estimated in seminal plasma. Results showed that mean the α-glucosidase activity was lowest among the azoospermic group with respect to oligozoospermic and normozoospermic groups. Mean zinc levels were also lower among azoospermics compared to oligozoospermic and normospermic groups. The difference was statistically significant (p<0.05). A significant positive correlation was observed between zinc levels and sperm count (r=0.29, p<0.05) and zinc and α-glucosidase activity (r=0.31, p<0.05) in seminal plasma. These results suggest that zinc and neutral α-glucosidase seem to play an important role in human reproduction.     

‘On-farm’ seed priming with zinc in chickpea and wheat in Pakistan

A series of on-station trials was implemented between 2002 and 2006 to assess the response of wheat (Triticum aestivum L.) and chickpea (Cicer arietinum) to zinc (Zn) added by soaking seeds (priming) in solutions of ZnSO₄ before sowing. Wheat seed was primed for 10 h in 0.3% Zn and chickpea for 6 h in 0.05% Zn. Seed treatments increased the seed concentration in wheat from 27 to 470 mg/kg and in chickpea from 49 to 780 mg/kg. Priming wheat seeds with 0.3% Zn significantly increased the mean shoot dry mass, Zn concentration and Zn uptake of 15-day-old seedlings relative to non-primed controls and seeds primed with water alone. Using 0.4% Zn further increased shoot Zn concentration but depressed shoot dry mass to the level of the non-primed control. In seven trials, mean grain yield of wheat was significantly increased from 2.28 to 2.42 t/ha (6%) by priming with water alone and to 2.61 t/ha (14%) by priming with 0.3% Zn. Mean grain yield of chickpea in seven trials was increased significantly from 1.39 to 1.65 t/ha (19%) by priming seeds with 0.05% Zn. The effect of priming chickpea seeds with water was intermediate (1.49 t/ha) and not statistically separable from the non-primed and zinc-primed treatments. Increased grain yield due to priming in both crops was associated with increases in total biomass but there was no significant effect of priming on harvest index. In addition to increasing yield, priming seeds with Zn also significantly increased grain zinc concentration, by 12% in wheat (mean of three trials) and by 29% in chickpea (one trial) and the total amount of Zn taken up by the grain (by 27% in wheat and by 130% in chickpea). Using ZnSO₄ to prime seeds was very cost-effective, with net benefit-to-cost ratios of 75 for wheat and 780 for chickpea. An erratum to this article can be found at     

Mapping QTLs and candidate genes for iron and zinc concentrations in unpolished rice of Madhukar×Swarna RILs

Identifying QTLs/genes for iron and zinc in rice grains can help in biofortification programs. 168 F(7) RILs derived from Madhukar×Swarna were used to map QTLs for iron and zinc concentrations in unpolished rice grains. Iron ranged from 0.2 to 224ppm and zinc ranged from 0.4 to 104ppm. Genome wide mapping using 101 SSRs and 9 gene specific markers showed 5 QTLs on chromosomes 1, 3, 5, 7 and 12 significantly linked to iron, zinc or both. In all, 14 QTLs were identified for these two traits. QTLs for iron were co-located with QTLs for zinc on chromosomes 7 and 12. In all, ten candidate genes known for iron and zinc homeostasis underlie 12 of the 14 QTLs. Another 6 candidate genes were close to QTLs on chromosomes 3, 5 and 7. Thus the high priority candidate genes for high Fe and Zn in seeds are OsYSL1 and OsMTP1 for iron, OsARD2, OsIRT1, OsNAS1, OsNAS2 for zinc and OsNAS3, OsNRAMP1, Heavy metal ion transport and APRT for both iron and zinc together based on our genetic mapping studies as these genes strictly underlie QTLs. Several elite lines with high Fe, high Zn and both were identified.     

Molecular modeling of zinc and copper binding with Alzheimer’s amyloid β-peptide

Aggregation of the amyloid β-peptide (Aβ) into insoluble fibrils is a key pathological event in Alzheimer’s disease. Cu(II) and Zn(II) ions were reported to be able to induce Aβ aggregation at nearly physiological concentrations in vitro. In this study, the binding modes of Cu(II) and Zn(II) in this process were explored by molecular modeling. In the pre-associated Aβ, Nτ atom of imidazole ring of His14, O atom of carbonyl of main-chain and two O atoms of water occupied the four ligand positions of the complex. While in the aggregated form of Aβ, the His13(N)–Metals–His14(N) bridges were formed through metal cross-linking action. These results would be helpful to put insight on revealing the formation mechanism of pathogenic Aβ aggregates in brain.     

Role of zinc and copper ions in the pathogenetic mechanisms of Alzheimer’s and Parkinson’s diseases

Disbalance of zinc (Zn²⁺) and copper (Cu²⁺) ions in the central nervous system is involved in the pathogenesis of numerous neurodegenerative disorders such as multisystem atrophy, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, Wilson-Konovalov disease, Alzheimer’s disease, and Parkinson’s disease. Among these, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most frequent age-related neurodegenerative pathologies with disorders in Zn²⁺ and Cu²⁺ homeostasis playing a pivotal role in the mechanisms of pathogenesis. In this review we generalized and systematized current literature data concerning this problem. The interactions of Zn²⁺ and Cu²⁺ with amyloid precursor protein (APP), β-amyloid (Abeta), tau-protein, metallothioneins, and GSK3β are considered, as well as the role of these interactions in the generation of free radicals in AD and PD. Analysis of the literature suggests that the main factors of AD and PD pathogenesis (oxidative stress, structural disorders and aggregation of proteins, mitochondrial dysfunction, energy deficiency) that initiate a cascade of events resulting finally in the dysfunction of neuronal networks are mediated by the disbalance of Zn²⁺ and Cu²⁺.     

The reaction of zinc sulphide with ionic copper—the biological implications. Part 1. Surface area studies of zinc sulphide and its reaction with copper complexes and copper containing proteins

The role of metal sulphides vis-à-vis the availability of dietary copper in ruminant animals has been investigated using zinc sulphide as a model metal sulphide and a selection of copper complexes and copper containing proteins as models for sources of dietary copper. The extent of reactivity of zinc sulphide towards the copper complexes is dependent upon the type of donor atom co-ordinated to copper:

The order to reactivity is found to be CuO > CuN > CuS complexes and is in keeping with the reported values for the instability constant pK_n of the complexes. In contrast, no reaction is observed between zinc sulphide and the copper containing proteins studied (azurin, superoxide dismutase and cerulophasmin) and is attributed to the protection of the copper centres by the protein backbone. The results facilitate an understanding of copper metabolism in ruminants and a mechanism is proposed for the removal of dietary copper sources in such species.Reactions between copper(II) sulphate solutions and samples of zinc sulphide having a range of specific surface areas (prepared by sintering at differing temperatures) have been studied. The fact that the reactivity is found to be highly dependent upon the specific surface area of the metal sulphide may well be of significance when considering the fate of copper in sulphur-rich biological systems.