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PubMed1993

Prevention of carcinogenicity of anticancer drugs by metallothionein induction.

We examined the efficacy of metallothionein induction in the prevention of the carcinogenic action of cis-platinum and melphalan administered repeatedly to mice over a relatively long period. The increased pulmonary metallothionein induced by bismuth or zinc compounds during the period of chemotherapy with cis-platinum or melphalan protected the mice from carcinogenesis of these drugs in the lung. These results suggested the efficacy of metallothionein inducers in suppression of carcinogenicity considered as a secondary effect of anticancer agents in cancer chemotherapy.

Animals↗
PubMed1995

Differential effects of transforming growth factor-beta on osteoclast-like cell formation in mouse marrow culture: relation to the effect of zinc-chelating dipeptides.

The effect of transforming growth factor-beta (TGF-beta) on osteoclast-like cell formation in mouse marrow culture in vitro was investigated. The bone marrow cells were cultured for 7 days in alpha-minimal essential medium containing a well-known bone resorbing agent. Osteoclast-like cell formation was estimated with staining for tartrate-resistant acid phosphatase (TRACP), a marker enzyme of osteoclasts. The presence of TGF-beta (10(-13)-10(-11) M) caused a significant increase in the number of osteoclast-like multinucleated cells (MNCs); the maximum effect was seen with 10(-12) MTGF-beta. With a higher concentration (10(-10) M) of TGF-beta, the growth factor dramatically inhibited the 1,25-dihydroxyvitamin D5 [1,25(OH)2D3; 10(-8) M]-induced formation of osteoclast-like MNCs. This inhibitory effect was also seen in the formation of osteoclast-like MNCs stimulated by parathyroid hormone (10(-8) M), prostaglandine E2 (10(-6) M), and interleukin-1 alpha (50 U/ml). The stimulatory effect of TGF-beta (10(-12) M) on osteoclast-like MNCs formation was inhibited by zinc sulfate (10(-6) M) or zinc-chelating dipeptide [beta-alanyl-L-histidinato zinc (AHZ), 10(-6) M]. The stimulating effect of TGF-beta was markedly weakened by the presence of EGTA (0.5 mM), a chelator of Ca2+. The inhibitory effect of zinc compounds was not seen in the presence of EGTA. Moreover, the inhibitory effect of TGF-beta (10(-10) M), zinc sulfate (10(-6) M), or AHZ (10(-6) M) on osteoclast-like MNCs formation was not demonstrated in mature osteoclastic cells, although calcitonin (3 x 10(-8) M) significantly inhibited the osteoclastic formation. The present study demonstrates that TGF-beta has a stimulating and an inhibiting effect on osteoclast-like cell formation in mouse marrow culture, and that zinc can inhibit the stimulatory effect of TGF-beta.

Animals↗
PubMed2002

Electronic structure of reduced symmetry peripheral fused-ring-substituted phthalocyanines.

Reduced symmetry phthalocyanines are finding use in an increasing number of industrial applications. A detailed understanding of the electronic structure of the pi-system will greatly facilitate the design of new complexes, which fit the specifications required in many of these emerging high technology fields. NMR, electronic absorption, magnetic circular dichroism (MCD), and fluorescence emission and excitation spectra have been recorded for five generic metal phthalocyanine (MPc) derivatives in which additional benzene rings are fused either radially or obliquely onto at least one of the four peripheral benzo groups. The spectroscopy of four radially substituted compounds, zinc mononaphthotribenzotetraazaporphyrine (Zn3B1N), zinc monobenzotrinaphthotetraazaporphyrine (Zn1B3N), and two cis and trans zinc dibenzodinaphthotetraazaporphyrine (Zn2B2N) isomers, is compared to that of the obliquely fused structural isomer of Zn3B1N (Zn3BoN) and the D(4)(h)() symmetry parent compounds, ZnPc and zinc naphthalocyanine (ZnNc). The selection of Zn(II) as the central metal eliminates the possibility of charge transfer between the metal and ring. None of the complexes studied contain any sigma-bonded peripheral substituents. (1)H NMR signals of the seven compounds are assigned on the basis of the coupling patterns, integrated proton numbers, and decoupling experiments. The SIMPFIT program was used to perform spectral band deconvolution analyses of absorption and MCD spectra. ZINDO molecular orbital calculations are described, and the optical spectra are assigned on the basis of the MO models that have been developed previously to account for the spectral properties of metal porphyrin (MP(-2)) and metal phthalocyanine (MPc(-2)) complexes.

Algorithms↗
PubMed1995

Interaction of cis- and trans-diamminedichloroplatinum with metallothionein in vivo.

The properties of platinum (II) complexes to induce the biosynthesis of metallothionein (MT) were investigated in rabbits following injections of K2PtCl4, cis and trans isomers of DDP (diammine-dichloroplatinum). It was demonstrated that cis-DDP has an ability to induce MT specifically in the liver, whereas trans-DDP appears to be unable to stimulate the biosynthesis of MT in either the liver or the kidneys. In contrast, K2PtCl4 is effective to elevate the MT level in both tissues. However, all of these platinum complexes are rather poor stimulators for MT biosynthesis compared to cadmium and zinc compounds. Preinjection with Zn(NO3)2 significantly enhances the amount of Pt associated with the MT fractions compared to that resulting from injections with either cis- or trans-DDP without Zn(NO3)2 pretreatment. Metallothionein containing Pt was purified and identified from the liver and kidneys of rabbits after preinjections with Zn(NO3)2 followed by repeated injections of cis-DDP and trans-DDP, respectively. It was found for the first time that a relatively higher degree of Pt was associated with MT fractions in the case of trans-DDP treatment than that of cis-DDP injection. On this basis, the role of MT was discussed in relation to its involvement in the metabolism of cis-DDP, and the difference of the antitumor activity and toxicity between cis- and trans-DDP.

Animals↗
PubMed2000

Interference by toxic metal compounds with isolated zinc finger DNA repair proteins.

Compounds of nickel, cadmium, cobalt and arsenic have been shown previously to inhibit DNA repair processes at low concentrations. In the present study we investigated whether this repair inhibition may be caused by the displacement of zinc in zinc finger structures of DNA repair proteins. As models, the bacterial formamidopyrimidine-DNA glycosylase (Fpg) and the mammalian XPA protein were applied. Both proteins were inhibited by Cd(II) and Cu(II). Hg(II) strongly inhibited the Fpg protein, but did not affect the XPA protein. In contrast, the XPA protein was disturbed by Co(II) and Ni(II), while the activity of the Fpg protein was not reduced. Neither protein was inhibited by As(III) or Pb(II). Thus, each zinc finger protein appears to have its own structural features and sensitivities towards toxic metal ions. Furthermore, each metal exerts specific mechanisms leading to DNA repair inhibition.

Animals↗
PubMed2006

ZnO nanorods on in-situ synthesized ZnSe grains.

The ZnO nanorods grown on in-situ synthesized ZnSe grains through the chemical vapour deposition method are reported here for the first time. With a suitable growth condition, single crystal ZnO nanorods grow on the well-defined bounded facets of the random shape ZnSe grains using Zn and Se powders without any metal catalyst. The growth direction of ZnSe nanorods on a facet of a ZnSe grain is quite uniform. The synthesis mechanism of the ZnO nanorods on the ZnSe grains is proposed. The effects of the Se powder usage on the ZnO-ZnSe products and the photoluminescence of the products are investigated.

Crystallization↗
PubMedDate not supplied

Relationship between gastric levels and antiulcerogenic activity of zinc.

The relationship between the absorption of an organic zinc salt, zinc acexamate, and its antiulcerogenic activity in a model of cold-restraint stress was studied. Serum and gastric levels of zinc, as well as its antiulcerogenic effect, were determined after oral or intravenous administration of zinc acexamate. Cytochemical and X-ray microanalysis techniques were also applied. In the rats subjected to cold-restraint stress, gastric levels of zinc correlated with the antiulcerogenic effect observed after administration of zinc acexamate. However, it was not possible to establish a relationship between serum levels and the pharmacologic effect of zinc. Our results in animals subjected to regular diet indicate that the antiulcerogenic effect exhibited by zinc compounds could be associated with the presence of zinc at different levels of gastric tissue.

Administration, Oral↗
PubMed1997

[Cytocompatibility of dental alloys containing palladium].

The cytoxicity and the 50% lethal concentration (LC50) has been assessed in vitro by the colony forming method in extracts of 5 precious or semiprecious alloys and of oxides and chlorides of the metal contained in these alloys: Pd, Ag, Cu, Zn, Sn, In and Ga. All alloy extracts in culture medium induced cell death depending on their composition. In, Ga and Sn compounds showed the most favorable cell viability, Cu and Ag salts induced the lowest survival rate.

Biocompatible Materials↗
PubMed2006

Thermal degradation of acetate-intercalated hydroxy double and layered hydroxy salts.

Two hydroxy double salts (HDSs), zinc copper hydroxy acetate (ZCA) and zinc nickel hydroxy acetate (ZNA), and an analogous layered compound, zinc hydroxy acetate (ZHA), have been prepared by a coprecipitation method. The thermal degradation of these materials was characterized via thermogravimetric analysis (TGA), differential thermal analysis (DTA), and TGA coupled with Fourier transform infrared spectroscopy of gas-phase products, TGA-FTIR. Loss of physisorbed and interlayer H2O was observed between 50 and 150 degrees C for all compounds. Acetic acid, acetone, water, and CO2 were released at high temperatures with relative acetone yields found to be dependent on precursor identity, with very little formed from ZCA compared with ZHA and ZNA. Combined FTIR and XRD analysis of solid residues extracted at different points in the heating profile suggests that ketonization occurs via dissociative adsorption of acetic acid on ZnO surfaces. Nanometer-sized ZnO particles were formed from ZHA, showing slight preferential growth in the ZnO (002) lattice direction, while the presence of a second metal, Ni or Cu, served to retard ZnO crystallite growth at temperatures below 600 degrees C and eliminate preferential growth. ZCA leads to the formation of reduced copper species (metallic copper and Cu2O) when heated to 250 degrees C.

Journal Article↗
PubMed2006

Zinc requirements and the risks and benefits of zinc supplementation.

The adult human contains 2-3g of zinc, about 0.1% of which are replenished daily. On this basis and based on estimates of bioavailability of zinc, dietary recommendations are made for apparently healthy individuals. Absent chemical, functional, and/or physical signs of zinc deficiency are assumed indicative of adequacy. More specific data are seldom available. Changing food preferences and availability, and new food preparation, preservation, and processing technologies may require re-evaluation of past data. Conservative estimates suggest that 25% of the world's population is at risk of zinc deficiency. Most of the affected are poor, and rarely consume foods rich in highly bioavailable zinc, while subsisting on foods that are rich in inhibitors of zinc absorption and/or contain relatively small amounts of bioavailable zinc. In contrast, among the relatively affluent, food choice is a major factor affecting risk of zinc deficiency. An additional problem, especially among the relatively affluent, is risk of chronic zinc toxicity caused by excessive consumption of zinc supplements. High intakes of zinc relative to copper can cause copper deficiency. A major challenge that has not been resolved for maximum health benefit is the proximity of the recommended dietary allowance (RDA) and the reference dose (RfD) for safe intake of zinc. Present recommendations do not consider the numerous dietary factors that influence the bioavailability of zinc and copper, and the likelihood of toxicity from zinc supplements. Thus the current assumed range between safe and unsafe intakes of zinc is relatively narrow. At present, assessment of zinc nutriture is complex, involving a number of chemical and functional measurements that have limitations in sensitivity and specificity. This approach needs to be enhanced so that zinc deficiency or excess can be detected early. An increasing number of associations between diseases and zinc status and apparently normal states of health, where additional zinc might be efficacious to prevent certain conditions, point at the pharmacology of zinc compounds as a promising area. For example, relationships between zinc and diabetes mellitus are an area where research might prove fruitful. In our opinion, a multidisciplinary approach will most likely result in success in this fertile area for translational research.

Animals↗
PubMed2002

Zinc and iron interactions evaluated between different mineral sources in different nutritional matrixes.

We compared the absorption of BioZn, SFE-171, SO4Fe (reference standard) and SO4Zn (reference standard) alone or in combination in water and in an infant dessert. When mineral interactions were evaluated, zinc and iron were administered in a 1:1 molar relation. There 160 rats divided in 16 groups of 10 animals each which received: SO(4)65Zn, Bio65Zn, SO(4)65Zn + SO4Fe, Bio65Zn + SFE-171, SO(4)59Fe, 59SFE-171, SO(4)59Fe + SO4Zn and 59SFE-171 + BioZn either in water or an infant dessert. The results showed that BioZn has bioavailability similar to SO4Zn both in water (23.36 +/- 3.14% vs. 21.48 +/- 6.03%. respectively) and in an infant dessert (19.89 +/- 3.27% vs. 18.31 +/- 4.76%, respectively). When these zinc compounds were administered with iron no statistical difference of zinc absorption was found (Bio65Zn + SFE-171 in water 22.70 +/- 6.30%, Bio65Zn + SFE-171 in the infant dessert 18.07 +/- 5.89%, SO(4)65Zn + SO4Fe in water 24.67 +/- 5.70% and SO(4)65Zn + SO4Fe in the infant desert 20.56 +/- 5.20%). For iron, the absorption of 59SFE-171 in water was higher (p < .01) than SO(4)59Fe in water and 59SFE-171 + BioZn in water (32.35 +/- 8.32% vs. 26.27 +/- 8.83% vs. 23.69 +/- 8.37%, respectively). Iron absorption from SO(4)59Fe in water was higher (p < .01) than SO(4)59Fe + SO4Zn in water (26.27 +/- 8.83% vs. 20.21 +/- 8.72%, respectively). Iron absorption in the infant dessert was higher (p < .01) for 59SFE-171 + BioZn than SO(4)59Fe, 59SFE-171 and SO(4)59Fe + SO4Zn (22.81 +/- 6.97% vs. 16.12 +/- 6.14% vs. 16.90 +/- 6.23% vs. 15.04 +/- 6.25%, respectively). Statistical differences (p < .01) were found between iron absorption from 59SFE-171 in water and the infant dessert (32.35 +/- 8.32% vs. 16.90 +/- 6.23%, respectively) and for SO(4)59Fe (26.27 +/- 8.83% vs. 16.12 +/- 6.14% respectively). Zinc and iron interactions evaluated in a 1:1 molar relation of the minerals were observed only for iron absorption in water but not in infant dessert. No negative effect was found for zinc absorption neither in water nor in infant dessert.

Animals↗
PubMed1981

Ovine and bovine metallothioneins: accumulation and depletion of zinc in various tissues.

The accumulation and depletion of zinc in hepatic metallothionein (MT) and the accumulation of zinc with MT in various tissues were studied in the ovine and bovine species. It took 8 weeks for the accumulation of zinc to reach a plateau level of 270 microgram in MT per gram liver when a bull was fed a diet containing 2,000 ppm zinc. The half-lives of zinc in hepatic MT were found to be 24.1 and 22.6 days when a steer and a ewe, respectively, which had been fed the basal diet with 2,000 ppm zinc were changed to the basal diet without added zinc. Although zinc accumulated with all cytosolic zinc proteins, it accumulated to the greatest extent with MT, followed by a low molecular weight (MW) compound. Zinc accumulated with this low MW compound mostly in kidney and pancreas, and this accumulation was much greater in bovine than in ovine tissues. In both lambs and cattle, excess zinc accumulated with MT in liver, kidneys, pancreas and small and large intestinal epithelia, but not with MT in heart, testes, rumen papillae, abomasum mucosa or choroid plexus (cattle) when they were fed high dietary levels of zinc.

Animals↗
PubMed1994

Chlorophyll synthetase cannot synthesize chlorophyll a'.

Chlorophyll synthetase catalyzes the last step of chlorophyll biosynthesis, namely prenylation (esterification) of chlorophyllide with phytyl diphosphate or geranylgeranyl diphosphate. During investigation of various chlorophyllide derivatives as potential substrates we observed lower esterification with increasing percentages of chlorophyllide a' in epimeric mixtures of chlorophyllides a and a'. To avoid epimerization during esterification, we studied the reaction in detail with model compounds [zinc-13(2)(R)-methoxy-pheophorbide a and zinc-13(2)(S)-methoxy-pheophorbide a, zinc-13(2)(R)-methoxy-pyropheophorbide a and zinc-chlorine6-13(1), 15(2)-dimethylester]. We conclude that compounds which have the 13(2)-carbomethoxy group at the same side of the macrocycle as the propionic side chain of ring D are neither substrates nor competitive inhibitors. Only compounds having the 13(2)-carbomethoxy group at the opposite site are substrates for the enzyme. Naturally occurring chlorophyll a' must be formed by epimerization after esterification.

Carbon-Oxygen Ligases↗
PubMed2002

The oral anti-volatile sulphur compound effects of zinc salts and their stability constants.

Volatile sulphur compounds (VSC) produced in the oral cavity, are a major cause of oral malodour. Zinc (Zn) ions inhibit VSC formation. The objective of this study was to examine whether Zn salts with low stability constants were more suitable as sources of Zn in lozenges than salts with high stability constants. The former provide free Zn ions upon dissolution in water, whereas the latter provide almost no free Zn. Identical lozenges containing Zn-acetate and -gluconate, which have low stability constants, and Zn citrate and amino acid-chelated Zn, which have extremely high stability constants, were tested. All the lozenges contained 0.9% w/w Zn. Ten volunteers sucked the lozenges until dissolved, and oral VSC were measured by gas chromatography. Zn-acetate, -gluconate and -chelate had an impressive anti-VSC effect even 3 h after the lozenges were taken. Zn citrate had significantly less effect than the other lozenges except Zn acetate after 2 and 3 h. It was concluded that the anti-VSC effect was not related to the stability constants of the Zn compounds tested. Alternative ligands. with stronger affinity for Zn than the ligands in the lozenges, must be present in the oral cavity to explain these results. It is suggested that the sulphide ion may serve this function.

Adult↗
PubMed1996

[Characterization of low molecular weight zinc species in normal commercial vegetable foodstuffs].

In six different ordinary vegetables, namely kohlrabi, Chinese cabbage, chard, leak, spinach and Jerusalem artichoke, zinc was mainly found as low molecular weight species. In the present study, these important zinc compounds are further investigated. The determinations of the metal are performed by ET-AAS. The zinc complexes of all vegetables are anionic at pH 8.0 and show similar elution behaviour in gel permeation and anion exchange chromatography. Consequently, a great resemblance in structure between the low molecular weight zinc species from the different vegetables can be supposed. Exemplary, the zinc complexes of kohlrabi and Chinese cabbage are further examined. In more purified samples of these vegetables compared to zinc neither stoichiometric amounts of free protein amino acids nor nicotianamine, free malic acid, citric acid or phytic acid have been detected. Mainly glutamic acid is found in molar excess to zinc after acid hydrolysis in both cases. The cysteine contents of both zinc-binding fractions are very low. Conclusively, the well-known gamma-glutamylcysteinyl-glycines (phytochelatines) can not be responsible for the bonding of zinc in both ordinary vegetables. We suppose that zinc in kohlrabi and Chinese cabbage is bound to a glutamic acid derivative unknown as yet, possibly a malic acid ester.

Amino Acid Sequence↗
PubMed2005

Embryotoxicity of the antifouling biocide zinc pyrithione to sea urchin (Paracentrotus lividus) and mussel (Mytilus edulis).

The effects of the new antifouling compound zinc pyrithione (Zpt) on the embryonic development of sea urchin (Paracentrotus lividus) and mussel (Mytilus edulis) were investigated in laboratory toxicity tests. The median effective concentrations (EC50) were 7.7 nM for sea urchin embryos and 8 nM for mussel embryos. Toxic effects of Zpt on the larval growth of the sea urchin were detected at 0.5 nM. Predicted environmental concentrations of Zpt in pleasure craft harbours are higher than the predicted no effect concentrations for sea urchin and mussel embryos, indicating that Zpt may pose a threat to those species from exposure in the field.

Analysis of Variance↗
PubMed1986

Is aging inevitable? The intracellular zinc deficiency hypothesis of aging.

A review of the literature suggests that an intracellular zinc deficiency may be the primary cause of the aging process. Zinc-metalloenzymes play an important role in many aspects of cellular metabolism including DNA replication, repair and transcription. The main enzymes affected by zinc deficiency may be specific for each cell type. Depending on which zinc enzymes are "overvulnerable", zinc deficiency may result in accumulation of useless (or toxic) materials, malproduction of essential proteins, a neoplastic change or cell death, thus explaining the variability in aging patterns in different cell types. There is no simple and reliable index of zinc status in humans and a therapeutic trial may be needed to establish zinc deficiency. Finding a zinc-compound which can enter the cell and avoid the development of intracellular zinc deficiency may retard the aging process and postpone age-related diseases.

Aging↗
PubMed1989

Effects of zinc acexamate on blood flow and prostanoid levels in the gastric mucosa of the rat.

The effects of the new antiulcer compound zinc acexamate on blood flow and prostanoid levels in the gastric mucosa have been studied. Zinc acexamate (30 and 300 mg/kg) dose-dependently prevents the reduction induced by the perfusion of noradrenaline (3.5 micrograms/kg.min, 30 min) in gastric mucosal blood flow, as measured by 3H-aniline clearance. Zinc acexamate pretreatment also increases the levels of prostaglandin E2 in the gastric mucosa of the rat, both under control conditions and after infusion with noradrenaline. The levels of thromboxane A2 and prostacyclin were not modified by zinc acexamate. These results confirm the importance of microcirculation in pathogenesis and the idea that the antiulcer activity of zinc acexamate is due in part to its action in increasing the mechanism which defend the gastric mucosa against aggression.

Aminocaproates↗