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PubMed1998

Potent effect of zinc acexamate on bone components in the femoral-metaphyseal tissues of elderly female rats.

1. The effect of zinc compounds on bone components in the femoral-metaphyseal tissues from elderly female rats (50 weeks old) was investigated in vitro. Bone tissues were cultured for 24 hr in Dulbecco's modified Eagle medium containing either vehicle or zinc compounds (10[-7] to 10[-5] M). 2. Zinc content, alkaline phosphatase activity, deoxyribonucleic acid (DNA) and calcium contents in the metaphyseal tissues were significantly increased by the presence of zinc sulfate (10[-6] and 10[-5] M), beta-alanyl-L-histidinato zinc (AHZ; 10[-6] and 10[-5] M) and zinc acexamate (10[-7] to 10[-5] M). At 10[-5] M, the effect of zinc acexamate on the increase of bone components was more potent than that of zinc sulfate or AHZ. 3. The effect of zinc acexamate (10[-5] M) on the increase of alkaline phosphatase activity in the metaphyseal tissues was remarkable as compared with that of insulin (10[-8] M), estrogen (10[-9] M), insulin-like growth factor-I (10[-8] M), transforming growth factor-beta (10[-10] M), sodium fluoride (10[-3] M), dexamethasone (10[-7] M) and vitamin K2 (menaquinone-4; 10[-5] M) with an effective concentration. 4. The stimulatory effect of zinc acexamate (10[-5] M) on alkaline phosphatase activity and calcium content in the metaphyseal tissues was completely blocked by the presence of dipicolinate (10[-3] M), a chelator of zinc ion, and of cycloheximide (10[-6] M), an inhibitor of protein synthesis. 5. The present study demonstrates that zinc acexamate has a potent anabolic effect on bone components in the femoral-metaphyseal tissues from female elderly rats in vitro. The effect of zinc acexamate may be based in part on protein synthesis related to zinc ion in bone cells.

Alkaline Phosphatase↗
PubMed2006

Synthesis and structures of bimetallic and polymeric zinc coordination compounds supported by salicylaldiminato and anilido-aldimine ligands.

A series of bimetallic zinc complexes bearing salicylaldiminato (1b-3b) or anilido-aldimine (4c-5c) ligand frameworks, in which the metal centres are separated by aliphatic spacer groups containing 3-6 methylene units, were targeted. X-Ray analysis of salicylaldiminato derivative 2b, with a 4 carbon spacer group, revealed a coordination polymer in the solid state where each zinc centre is ligated by two salicylaldiminato ligands. Contrastingly, the structure of the anilido-aldimine complex 4c, with a 3 carbon methylene spacer group, was found to be a discrete bimetallic complex. These differences are attributed to the differing steric protection at the anilido vs phenoxy donors, the latter more readily facilitating bridges between metal centres.

Journal Article↗
PubMed1991

The antioxidant properties of a novel zinc-carnosine chelate compound, N-(3-aminopropionyl)-L-histidinato zinc.

A zinc-carnosine chelate compound, Z-103, attenuates gastric mucosal injuries and inhibits the increase of lipid peroxide in the gastric mucosa induced by burn shock or ischemia-reperfusion. However, the exact mechanism of the antioxidative effect of Z-103 is not clear. The antioxidant properties of a novel anti-peptic ulcer agent Z-103 in vitro were compared with those of zinc ion and L-carnosine. Z-103 scavenged superoxide anion radicals. Z-103 and ZnSO4, but not L-carnosine, inhibited the superoxide generation from polymorphonuclear leukocytes stimulated by opsonized zymosan, and also inhibited the generation of hydroxyl radicals by the Fenton reaction. The increase of lipid peroxides produced by rat brain homogenates and liver microsomes was also inhibited by Z-103 and ZnSO4. These findings indicate that the strong anti-ulcer and antioxidative actions of Z-103 in vivo are due to a combination of these antioxidant actions in vitro.

Anti-Ulcer Agents↗
PubMed2003

Inhibition of orally produced volatile sulfur compounds by zinc, chlorhexidine or cetylpyridinium chloride--effect of concentration.

Zinc ions, chlorhexidine (CHX) and cetylpyridinium chloride (CPC) are all known to inhibit production of volatile sulfur compounds (VSCs). The objective was to examine the anti-VSC dose-response effects of each of the above agents. Oral malodor was induced in 13 test subjects using the cysteine challenge method. The oral VSC response to rinses with 6 mm l-cysteine (pH 7.2) before and 1, 2 and 3 h after rinsing with zinc ions (Zn2+: 0.1, 0.3 and 1.0%), CHX and CPC (0.025 and 0.2%) was measured. Mouth air was analysed for VSC by gas chromatography (GC) according to current methodology. Zinc had a marked dose- and time-dependent anti-VSC effect. Zinc at 1% concentration had a somewhat unpleasant taste, whereas the lowest concentration was found acceptable. Chlorhexidine maintained a moderate anti-VSC effect over time. At 3 h, 0.2% CHX was the most effective agent but tasted relatively unpleasant. Cetylpyridinium at a concentration of 0.2% was only marginally more effective than 0.025% CHX over the 3 h, while 0.025% CPC had no better anti-VSC effect than water at both 2 h and 3 h. It was concluded that the three test agents demonstrated different anti-VSC kinetics. Although Zn had the best anti-VSC effect at 1 h, 0.2% CHX was at least as effective as 1% Zn at 3 h, most likely as a result of its unique substantivity.

Adult↗
PubMed2005

Interactions between different selenium compounds and zinc, cadmium and mercury.

In this paper, we present a polarographic study of systems containing different inorganic and organic selenium compounds (sodium selenite, sodium selenate, seleno-methionine and seleno-urea) and metal ions (Zn2+, Cd2+ Hg2+) of the 12th group of elements in the periodic table. While zinc is a trace element known to be essential for plants and animals, cadmium and mercury are exogenous elements and are harmful pollutants that accumulate during aging; selenium is also recognized as an important micronutrient and is sometimes added to the diet. Experiments investigating the interactions were carried out using polarographic techniques in unbuffered systems. The three metal cations originated complexes with different strength and solubility in the presence of selenite anions; in the presence of selenate, polarography was not able to detect formation of complexes with these metal ions, at least under the experimental conditions used: a decrease of Hg2+ ion concentration was observed. Seleno-methionine did not react with Cd2+; in the presence of Zn2+, a soluble complex with a co-ordination number 1 was formed, while, again, the concentration of Hg2+ decreased in the presence of increasing concentrations of the selenium derivative. Seleno-urea did not react with Zn2+, but formed a complex with Cd2+ with limited solubility. Finally, this ligand could not be studied with Hg2+ because of the overlapping of the reduction potentials of both the ligand and the metal cation. Overall equilibrium constants for complex formation (Kf) and the solubility product (Ksp) for poorly soluble species are also reported.

Cadmium↗
PubMed2005

Potentiometric, electronic structural, and ground- and excited-state optical properties of conjugated bis[(porphinato)zinc(II)] compounds featuring proquinoidal spacer units.

We report the synthesis, optical, electrochemical, electronic structural, and transient optical properties of conjugated (porphinato)zinc(II)-spacer-(porphinato)zinc(II) (PZn-Sp-PZn) complexes that possess intervening conjugated Sp structures having varying degrees of proquinoidal character. These supermolecular PZn-Sp-PZn compounds feature Sp moieties {(4,7-diethynylbenzo[c][1,2,5]thiadiazole (E-BTD-E), 6,13-diethynylpentacene (E-PC-E), 4,9-diethynyl-6,7-dimethyl[1,2,5]thiadiazolo[3,4-g]quinoxaline (E-TDQ-E), and 4,8-diethynylbenzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) (E-BBTD-E)} that regulate frontier orbital energy levels and progressively increase the extent of the quinoidal resonance contribution to the ground and electronically excited states, augmenting the magnitude of electronic communication between terminal (5,-10,20-di(aryl)porphinato)zinc(II) units, relative to that evinced for a bis[(5,5',-10,20-di(aryl)porphinato)zinc(II)]butadiyne benchmark (PZnE-EPZn). Electronic absorption spectra show significant red-shifts of the respective PZn-Sp-PZn x-polarized Q state (S0 --> S1) transition manifold maxima (240-4810 cm(-1)) relative to that observed for PZnE-EPZn. Likewise, the potentiometrically determined PZn-Sp-PZn HOMO-LUMO gaps (E1/2(0/+) - E1/2(-/0)) display correspondingly diminished energy separations that range from 1.88 to 1.11 eV relative to that determined for PZnE-EPZn (2.01 eV). Electronic structure calculations provide insight into the origin of the observed PZn-Sp-PZn electronic and optical properties. Pump-probe transient spectral data for these PZn-Sp-PZn supermolecules demonstrate that the S1 --> S(n) transition manifolds of these species span an unusually broad spectral domain of the NIR. Notably, the absorption maxima of these S1 --> S(n) manifolds can be tuned over a 1000-1600 nm spectral region, giving rise to intense excited-state transitions approximately 4000 cm(-1) lower in energy than that observed for the analogous excited-state absorption maximum of the PZnE-EPZn benchmark; these data highlight the unusually large quinoidal resonance contribution to the low-lying electronically excited singlet states of these PZn-Sp-PZn species. The fact that the length scales of the PZn-Sp-PZn species (approximately 25 angstrom) are small with respect to those of classic conducting polymers, yet possess NIR S1 --> S(n) manifold absorptions lower in energy, underscore the unusual electrooptic properties of these conjugated structures.

Electrochemistry↗
PubMed1990

[Development of an inactivated vaccine for the protection of cattle against Aujeszky's disease].

The effects of an inactivated strain of Aujeszky's disease vaccine in cattle were investigated. It has not been possible to use vaccines licensed for use in pigs successfully in cattle even though cattle develop neutralizing antibodies to these vaccines. The addition of zinc compounds to the vaccines resulted in protection in cattle. The basis for the use of zinc is discussed. A mutant based vaccine was effective following local administration, but was not when administered parenterally. Anti-prostaglandin was not effective either, despite its successful use in sheep when administered with BHV1. The vaccine presents a prospect for immunising dogs and cats, and the addition of zinc compounds to other drugs and inducers is discussed.

Animals↗
PubMed1992

Two new sterically hindered phthalocyanines: synthetic and photodynamic aspects.

The synthesis and the properties of 1,4-dibutoxy-2,3-dicyanotriptycene, of a metal-free tetradibenzobarrelenooctabutoxyphthalocyanine, and of the corresponding zinc phthalocyanine are described. The two phthalocyanines do not aggregate when dissolved in benzene at concentrations up to 450 microM. For the metal-free and the zinc compounds, the red band maxima are at 736 and 757 nm, the triplet maxima are at 590 and 605 nm, the triplet state lifetimes are 58 and 177 microseconds, and the protoporphyrin-IX dimethyl ester-to-compound bimolecular rate constants for triplet energy transfer are 2.61 x 10(8) and 1.47 x 10(8) M-1 s-1. Triplet energy transfer from the metal-free compound to O2 is endoergonic by 1.0 kcal mol-1. The potential of the zinc compound for photodynamic therapy is touched upon.

Energy Transfer↗
PubMed2000

Bioavailability, biodistribution, and toxicity of BioZn-AAS(1): a new zinc source. comparative studies in rats.

Food fortification with a proper zinc compound is an economic and effective strategy to prevent zinc deficiency. BioZn-AAS, a zinc gluconate stabilized with glycine, was compared with zinc sulfate (reference standard), zinc hydroxide, and zinc gluconate, all of them labeled with (65)Zn. This preclinical study was performed on Sprague-Dawley rats of both sexes, and the administered dose was 85 microg/kg of zinc. Bioavailability studies showed that absorption of BioZn-AAS was not statistically different than absorption from other sources in female rats (25.65% +/- 2.20% for BioZn-AAS, 28.24% +/- 4. 60% for ZnSO(4), 24.91% +/- 4.02% for Zn[OH](2), and 25.51% +/- 2. 70% for Zn-gluconate). In the case of the male rats, absorption of BioZn-AAS (27.97% +/- 4.20%) was higher (P<0.05) than that from the other compounds (23.15% +/- 2.90% for ZnSO(4), 22.62% +/- 3.90% for Zn[OH](2), and 22.30% +/- 3.90% for Zn-gluconate). Biodistribution studies demonstrated that the zinc from BioZn-AAS followed the same metabolic pathway as zinc from the other sources. Toxicity studies were performed with 50 female and 50 male rats. The value of oral lethal dose 50 (LD(50)) was 2000 mg/kg for female rats and 1900 mg/kg for male rats. Therefore, we conclude that BioZn-AAS has adequate properties to be considered a proper zinc compound for food fortification or dietary supplementation.

Absorption↗
PubMed2005

Enzymes of the last steps of chlorophyll biosynthesis: modification of the substrate structure helps to understand the topology of the active centers.

Enzymes catalyzing two of the late steps of chlorophyll biosynthesis are NADPH:protochlorophyllide oxidoreductase (POR), responsible for the light-dependent reduction of protochlorophyllide to chlorophyllide, and chlorophyll synthase that catalyses the esterification of chlorophyllide to chlorophyll. Inhibitors of these enzymes are of interest as potential herbicides. Both enzymes presumably form a complex, and the question arose whether chlorophyll synthase can react with chlorophyllide while it is still bound to POR. Here, we describe the chemical modification of protochlorophyllides and chlorophyllides with space-filling substituents at rings A, B, and E of the tetrapyrrole macrocycle and the reactivity of the modified substrates. Both enzymes tolerate the large and flexible phenylamino substituent at ring B, indicating that ring B points toward the enzyme surface while the substrate is bound. On the basis of the standard compound zinc protopheophorbide a (100% activity), the 7(1)-phenylamino derivative shows a comparable activity (83%) with POR that is higher than that of the parent formyl derivative zinc protopheophorbide b (58% activity). In contrast, the 3(1)-phenylamino derivative is less active (12%) than the parent formyl compound zinc protopheophorbide d (49% activity), indicating that the binding pocket leaves less space around ring A than around ring B. Almost no space must be left around ring E because substitution of the 13(2)-carboxymethyl ester (100% activity) by the 13(2)-carboxyethyl ester reduces the activity to 0.2%. Chlorophyll synthase leaves somewhat more space around ring E on the A side of the tetrapyrrole in the binding pocket; substitution of the 13(2)-proton (100% activity) by a methoxy group (53% activity) and an ethoxy group (11% activity) is tolerated to a certain extent, while the carbomethoxy group in this position is not accepted. Opening of ring E to a chlorin e6 dimethylester is tolerated (39% activity), while the large benzylamide residue at this site leads to the loss of activity. We conclude that the tetrapyrroles bind to both enzymes in the same direction: rings C, D, and E are oriented to the interior of the binding cleft, and rings A and B are oriented to the surface of the enzyme; this excludes simultaneous binding to both enzymes.

Bacterial Proteins↗
PubMed1999

Stimulatory effect of zinc acexamate administration on fracture healing of the femoral-diaphyseal tissues in rats.

The effect of zinc acexamate on fracture healing of the femoral-diaphyseal tissues in rats was investigated in vivo. Zinc acexamate (0.3 and 10.0 mg Zn/100 g body weight per day) was orally administered to rats (4 weeks old) surgically fractured the femoral diaphysis for 14 to 28 days. Calcium content and alkaline phosphatase activity in the femoral-diaphyseal tissues were significantly decreased in rats with fracture healing, while bone acid phosphatase activity and protein content were markedly increased. The administration of zinc acexamate (10.0 mg Zn/100 g) for 28 days caused a significant increase in calcium content, alkaline and acid phosphatases activities, protein and deoxyribonucleic acid (DNA) contents in the femoral-diaphyseal tissues of rats with fracture healing. With the lower dose (3.0 mg Zn/100 g), zinc compound had a partial effect on bone components. Femoral mineral density in rats with fracture healing was significantly increased by the administration of zinc acexamate (10.0 mg Zn/100 g) for 28 days. Femoral-diaphyseal zinc content was significantly decreased in rats with fracture healing. This decrease was completely restored by the administration of zinc acexamate (10.0 mg Zn/100 g) for 28 days. The present study suggests that the supplement of zinc compound stimulates fracture healing of the femoral-diaphyseal tissues in rats.

Acid Phosphatase↗
PubMed1992

Effects of cadmium, copper and metallothionein synthesis inhibiting and stimulating compounds on zinc uptake and accumulation in rat hepatoma HTC cells.

Experiments were carried out to investigate the uptake and accumulation of Zn in rat hepatoma HTC cells, as affected by interfering metals (Cd, Cu), metallothionein synthesis inhibiting compounds (Actinomycin D, cycloheximide) and metallothionein synthesis stimulating compounds (dexamethasone, dibu-cAMP). Cell viability was tested under all experimental conditions by the measurement of LDH leakage, K+ uptake and total cell protein. Determinations of Zn were performed by AAS (total Zn) or by gamma-ray spectrometry (65Zn). Metallothionein analysis was carried out by Cd-saturation tests. The results indicate that cellular responses in rat hepatoma HTC cells with respect to the uptake and accumulation of 65Zn are fully comparable with literature data existing for 65Zn accumulation in rat hepatocytes, under all experimental conditions applied. Cu2+ and dibutyryl-cAMP did not significantly affect rates of 65Zn accumulation. Cd2+, Actinomycin D and cycloheximide reduced 65Zn uptake, but dexamethasone additions resulted in increased 65Zn accumulation in the cells. Effects on 65Zn were shown both in cytosolic and in the membranes/organelles cell fractions. HPLC chromatography in control cells suggested that newly accumulated cytosolic 65Zn was predominantly MT-associated. Dexamethasone-induced 65Zn accumulation could not be related to elevated cellular MT levels, nor were the total cytosolic Zn levels significantly affected. Non-specific attenuations in MT levels (Actinomycin D, cycloheximide and dibu-cAMP) yielded linear relations between cytosolic 65Zn and MT levels, without any change in cytosolic Zn (AAS). Combined addition of Cd and dexamethasone yielded elevated MT levels, but severely reduced total cytosolic Zn and 65Zn concentrations. The results further indicate the non-Zn-specific nature of dexamethasone-action and suggest the relatively easy Zn-complexing and Zn-release of MT. The simultaneous determinations of total cytosolic zinc and cytosolic 65Zn levels showed that the application and sole measurement of radiotracers may yield only one-sided views of what is actually present or occurring in the cells.

Animals↗
PubMed1980

Inhibition by zinc of hepatic lysosomal release of beta-glucuronidase induced by phorbol-12-myristate-13-acetate (PMA).

The tumor promoter, phorbol-12-myristate-13-acetate (PMA), elicited a significant increase in lysosomal membrane permeability, as measured by release of free beta-glucurnidase, in guinea pig and hamster isolated hepatic lysosomes in vitro. This response was antagonized by zinc sulfate; zinc compounds having previously been shown to inhibit tumor growth at multiple sites in several species. Since phorbol ester tumor promotion is likely associated in part with actions on cellular membrane systems, its inhibition by zinc may relate to the membrane stabilizing activity of zinc compounds.

Animals↗
PubMed2004

Highly conjugated (polypyridyl)metal-(porphinato)zinc(II) compounds: long-lived, high oscillator strength, excited-state absorbers having exceptional spectral coverage of the near-infrared.

Transient dynamical studies of ruthenium(II) [5-(4'-ethynyl-(2,2';6',2' '-terpyridinyl))-10,20-bis(2',6'-bis(3,3-dimethyl-1-butyloxy)phenyl)porphinato]zinc(II)-(2,2';6',2' '-terpyridine)2+ bis-hexafluorophosphate (Ru-PZn), osmium(II) [5-(4'-ethynyl-(2,2';6',2' '-terpyridinyl))-10,20-bis(2',6'-bis(3,3-dimethyl-1-butyloxy)phenyl)porphinato]zinc(II)-(2,2';6',2' '-terpyridine)2+ bis-hexafluorophosphate (Os-PZn), ruthenium(II) [5-(4'-ethynyl-(2,2';6',2' '-terpyridinyl))-15-(4'-nitrophenyl)ethynyl-10,20-bis(2',6'-bis(3,3-dimethyl-1-butyloxy)phenyl)porphinato]zinc(II)-(2,2';6',2' '-terpyridine)2+ bis-hexafluorophosphate (Ru-PZn-A), osmium(II) [5-(4'-ethynyl-(2,2';6',2' '-terpyridinyl))-15-(4'-nitrophenyl)ethynyl-10,20-bis(2',6'-bis(3,3-dimethyl-1-butyloxy)phenyl)porphinato]zinc(II)-(2,2';6',2' '-terpyridine)2+ bis-hexafluorophosphate (Os-PZn-A), and ruthenium(II) [5-(4'-ethynyl-(2,2';6',2' '-terpyridinyl))-ruthenium(II)-15-(4'-ethynyl-(2,2';6',2' '-terpyridinyl))-10,20-bis(2',6'-bis(3,3-dimethyl-1-butyloxy)phenyl)porphinato]zinc(II)-bis(2,2';6',2' '-terpyridine)4+ tetrakis-hexafluorophosphate (Ru-PZn-Ru), and ruthenium(II) [5-(4'-ethynyl-(2,2';6',2' '-terpyridinyl))-osmium(II)-15-(4'-ethynyl-(2,2';6',2' '-terpyridinyl))-10,20-bis(2',6'-bis(3,3-dimethyl-1-butyloxy)phenyl)porphinato]zinc(II)-bis(2,2';6',2' '-terpyridine) tetrakis-hexafluorophosphate (Ru-PZn-Os) show that these highly conjugated supermolecular chromophores feature electronically excited states that absorb over broad NIR spectral windows with considerable oscillator strength and manifest lifetimes (1-50 mus) that are extraordinarily long relative to those of classic low band-gap organic materials. The excited-state absorptive domains of these strongly coupled multipigment ensembles can be extensively modulated. For sequential one-photon absorptive processes, these compounds evince large sigmae, sigmae/sigmag, and sigmae - sigmag values. As the combination of all these properties within single chromophoric entities have heretofore lacked precedent within the NIR, these and closely related structures may find particular utility in a variety of technologically important optical-limiting applications.

Journal Article↗
PubMed1975

[Determination of metabolic availability of zinc and estimation of zinc requirements through changes in the activity of metallo-zinc enzymes].

Data on the zinc requirements of animals vary widely with the type of diet or kind of zinc compound considered, as they are dependent on the kind of definition and estimation of mineral requirements used which, in turn, are based on the analytical content of the mineral in the diet. Actually, requirements for a particular trace element are the same for any diet provided differences in the rate of absorption and metabolic availability of the element are taken into consideration. A suggestion is made in the present paper to utilize changes in the activity of different metallo-zinc enzymes as a method for determining the degree of metabolic availability of zinc. Within the framework of a repletion trial young male rats were fed a semisynthetic casein diet containing 1.2 ppm of zinc for a 14-day period of zinc depletion followed by a 15-day repletion period during which the rats received a diet containing 4.5 ppm or 12 ppm of zinc. In this trial the pattern of activity of the alkaline phosphatase in serum and in the femoral bones was studied and the level of pancreatic carboxypeptidase A and B was estimated. The data thus obtained were compared with those of pair-fed control animals and control animals fed a libitum. (96 ppm of dietary zinc). The results of the present trial show the metabolic availability of zinc can be determined by measuring the level of activity of these metallo-zinc enzymes. A suitable model was established. Moreover, attempts have been made to show in which way the zinc demands of growing, full-grown, pregnant and lactating animals may be estimated by measuring changes in the degree of activity of these metallo-zinc enzymes. A definition is, in this case, given by that amount of zinc which allows for an optimum activity of the different metallo-zinc enzymes. Such data are applicable only to a particular diet or are valid only for a particular zinc compound. Principally, it is much better to relate the Zn requirements of the animal to the level of absorbable and metabolically available zinc. The present model has been suggested to provide a possibility for measuring the metabolic availability of zinc in the body.

Alkaline Phosphatase↗