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Results for “Zinc Compounds”

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PubMed1986

Investigation of the potential carcinogenicity of a range of chromium containing materials on rat lung.

Twenty one chromium containing materials were examined for carcinogenic activity in a two year study using an intrabronchial pellet implantation system whereby pellets loaded with test material were surgically implanted into the lower left bronchus of rats. The principal aim of the study was to extend our knowledge of the carcinogenic potential of chromium compounds and, in particular, chromates (Cr6+). A statistically significant incidence of treatment related lung tumours was found with some sparingly soluble chromate materials. All tumours were large keratinizing squamous carcinomas of the left lung, except for a single left lung adenocarcinoma and two left lung anaplastic carcinomas. No bronchial carcinomas (0/100) were seen in the negative control group (blank pellet loaded with cholesterol), whereas bronchial carcinomas (22/48 and 25/100) occurred in the two positive control groups which received pellets loaded with 20-methylcholanthrene and calcium chromate respectively. Among the 20 test materials, only three groups gave statistically significant numbers of bronchial carcinomas. Two of these were groups receiving different samples of strontium chromate which gave 43/99 and 62/99 tumours. The third group, zinc chromate (low solubility), gave 5/100 bronchial carcinomas. A further zinc chromate group (Norge composition) produced 3/100 bronchial carcinomas which was not statistically significant. A few lung tumours were observed in other test groups.

Animals↗

PubMed2004

Inhibition of alpha-chymotrypsin with thiol-bearing substrate analogues in the presence of zinc ion.

We have demonstrated that thiol-bearing analogues of alpha-chymotrysin (alpha-CT) substrates such as (S)-(1-benzyl-2-thiolethyl)-carbamic acid, benzyl ester (3) inhibits alpha-CT, a prototypical serine protease, in the presence of Zn(II) ion. They constitute a novel class of small molecule inhibitors for alpha-CT believed to inhibit the enzyme by forming a ternary complex consisting of alpha-CT, Zn(II) ion, and the inhibitor.

Chymotrypsin↗

PubMed2004

Dose-dependent transitions in mechanisms of toxicity: case studies.

Experience with dose response and mechanisms of toxicity has shown that multiple mechanisms may exist for a single agent along the continuum of the full dose-response curve. It is highly likely that critical, limiting steps in any given mechanistic pathway may become overwhelmed with increasing exposures, signaling the emergence of new modalities of toxic tissue injury at these higher doses. Therefore, dose-dependent transitions in principal mechanisms of toxicity may occur, and could have significant impact on the interpretation of reference data sets for risk assessment. To illustrate the existence of dose-dependent transitions in mechanisms of toxicity, a group of academic, government, and industry scientists, formed under the leadership of the ILSI Health and Environmental Sciences Institute (HESI), developed a series of case studies. These case studies included acetaminophen, butadiene, ethylene glycol, formaldehyde, manganese, methylene chloride, peroxisome proliferator-activated receptor (PPAR), progesterone/hydroxyflutamide, propylene oxide, vinyl acetate, vinyl chloride, vinylidene chloride, and zinc. The case studies formed the basis for technical discourse at two scientific workshops in 2003.

Acetaminophen↗

PubMed2005

Perinatal omega-3 polyunsaturated fatty acid supply modifies brain zinc homeostasis during adulthood.

Dietary omega-3 polyunsaturated fatty acid (PUFA) influences the expression of a number of genes in the brain. Zinc transporter (ZnT) 3 has been identified as a putative transporter of zinc into synaptic vesicles of neurons and is found in brain areas such as hippocampus and cortex. Neuronal zinc is involved in the formation of amyloid plaques, a major characteristic of Alzheimer's disease. The present study evaluated the influence of dietary omega-3 PUFA on the expression of the ZnT3 gene in the brains of adult male Sprague-Dawley rats. The rats were raised and/or maintained on a control (CON) diet that contained omega-3 PUFA or a diet deficient (DEF) in omega-3 PUFA. ZnT3 gene expression was analyzed by using real-time PCR, free zinc in brain tissue was determined by zinquin staining, and total zinc concentrations in plasma and cerebrospinal fluid were determined by atomic absorption spectrophotometry. Compared with CON-raised animals, DEF-raised animals had increased expression of ZnT3 in the brain that was associated with an increased level of free zinc in the hippocampus. In addition, compared with CON-raised animals, DEF-raised animals had decreased plasma zinc level. No difference in cerebrospinal fluid zinc level was observed. The results suggest that overexpression of ZnT3 due to a perinatal omega-3 PUFA deficiency caused abnormal zinc metabolism in the brain. Conceivably, the influence of dietary omega-3 PUFA on brain zinc metabolism could explain the observation made in population studies that the consumption of fish is associated with a reduced risk of dementia and Alzheimer's disease.

Animals↗

PubMed2005

Tris(thioimidazolyl)borate-zinc-thiolate complexes for the modeling of biological thiolate alkylations.

The S3Zn-SR coordination of thiolate-alkylating enzymes such as the Ada DNA repair protein was reproduced in tris(thioimidazolyl)borate-zinc-thiolate complexes Tti(R)Zn-SR'. Four different Tti(R) ligands and nine different thiolates were employed, yielding a total of 12 new complexes. In addition, one Tti(R)Zn-SH complex and two thiolate-bridged [Tti(R)-SEt-Tti(R)]+ complexes were obtained. A selection of six thiolate complexes was converted with methyl iodide to the corresponding methyl thioethers and Tti(R)Zn-I. According to a kinetic analysis these reactions are second-order processes, which implies that the alkylations are likely to occur at the zinc-bound thiolates. They are much faster than the alkylations of zinc thiolates with N3 or N2S tripod ligands. The most reactive thiolate, Tti(Xyl)Zn-SEt, reacts slowly with trimethyl phosphate in a nonpolar medium at room temperature, yielding methyl-ethyl-thioether and Tti(Xyl)Zn-OPO(OMe)2 which can be converted back to the thiolate complex with NaSEt. This is the closest reproduction of the Ada repair process so far.

Alkylation↗

PubMed1998

The mechanism of catalysis and the inhibition of the Bacillus cereus zinc-dependent beta-lactamase.

The plot of kcat/Km against pH for the Bacillus cereus 569/H beta-lactamase class B catalysed hydrolysis of benzylpenicillin and cephalosporin indicates that there are three catalytically important groups, two of pKa 5.6+/-0.2 and one of pKa 9.5+/-0.2. Below pH 5 there is an inverse second-order dependence of reactivity upon hydrogen ion concentration, indicative of the requirement of two basic residues for catalysis. These are assigned to zinc(II)-bound water and Asp-90, both with a pKa of 5.6+/-0.2. A thiol, N-(2'-mercaptoethyl)-2-phenylacetamide, is an inhibitor of the class B enzyme with a Ki of 70 microM. The pH-dependence of Ki shows similar pH inflections to those observed in the catalysed hydrolysis of substrates. The pH-independence of Ki between pH 6 and 9 indicates that the pKa of zinc(II)-bound water must be 5.6 and not the higher pKa of 9.5. The kinetic solvent isotope effect on kcat/Km is 1.3+/-0.5 and that on kcat is 1.5. There is no effect on reactivity by either added zinc(II) or methanol. The possible mechanisms of action for the class B beta-lactamase are discussed, and it is concluded that zinc(II) acts as a Lewis acid to stabilize the dianionic form of the tetrahedral intermediate and to provide a hydroxide-ion bound nucleophile, whereas the carboxylate anion of Asp-90 acts as a general base to form the dianion and also, presumably, as a general acid catalyst facilitating C-N bond fission.

Acetamides↗

PubMed2005

DESCRIPTIVE ANALYSIS OF DIVALENT SALTS.

Many divalent salts (e.g., calcium, iron, zinc), have important nutritional value and are used to fortify food or as dietary supplements. Sensory characterization of some divalent salts in aqueous solutions by untrained judges has been reported in the psychophysical literature, but formal sensory evaluation by trained panels is lacking. To provide this information, a trained descriptive panel evaluated the sensory characteristics of 10 divalent salts including ferrous sulfate, chloride and gluconate; calcium chloride, lactate and glycerophosphate; zinc sulfate and chloride; and magnesium sulfate and chloride. Among the compounds tested, iron compounds were highest in metallic taste; zinc compounds had higher astringency and a glutamate-like sensation; and bitterness was pronounced for magnesium and calcium salts. Bitterness was affected by the anion in ferrous and calcium salts. Results from the trained panelists were largely consistent with the psychophysical literature using untrained judges, but provided a more comprehensive set of oral sensory attributes.

Journal Article↗

PubMed1991

[The effect of diabetogenic substances on the zinc and calcium content in the pancreatic islet cells of rabbits].

The injections of diabetogenic drugs to rabbits induced a decrease in zinc and calcium content in B insulocytes dependent on the degree of these cells damage and hyperglycemia. The content of these metals in A insulocytes was not significantly altered due to a light injury of these cells. A high concentration of calcium in islet A cells is suggested to be a protective factor to the action of alteration agents.

Aminoquinolines↗

PubMed2003

Galvanic interaction between gold and amalgam: effect of zinc, time and surface treatments.

BACKGROUND: Previous studies have investigated the electrolytic action of oral electrogalvanism. However, the reasons why certain treatments or materials are successful in reducing galvanic current have not been addressed fully. This study assessed galvanic current with several materials, surface conditions and treatments. METHODS: The authors measured galvanic currents between a type 3 cast gold alloy and Dispersalloy Dispersed Phase Alloy (zinc) (Dentsply Caulk, Milford, Del.) under different surface conditions using a zero-resistance-ammeter technique in a synthetic saliva solution for 10 hours. In addition, the galvanic currents between the same gold and Tytin alloy (non-zinc) (Kerr, Orange, Calif.), experimental zinc alloy (same makeup as that of Tytin, with the addition of zinc) and non-zinc dispersed-phase experimental alloy (essentially the same physical and chemical makeup as that of Dispersalloy, with the exclusion of zinc) were measured. Triplicate tests were performed for each condition. RESULTS: The statistical analysis indicated that electrogalvanic activity is reduced significantly when the amalgam surface is treated with tin oxide or silver nitrate. Both zinc-containing amalgams in their as-carved condition exhibited higher anodic charge densities than did their zinc-free counterparts. Galvanic current measured in Dispersalloy was reduced with the passage of time after carving. CONCLUSION: Galvanic interaction between cast gold and amalgam is reduced with time and surface treatments, but is increased considerably when the amalgam contains zinc. CLINICAL IMPLICATIONS: Amalgam restorations containing zinc that are in contact with gold restorations occasionally elicit galvanic pain. Selection of a non-zinc-containing amalgam will reduce the level of galvanic interaction. Galvanic pain from occlusal contact is reduced or eliminated when the restoration is brushed with tin oxide immediately after carving or is treated with 2 percent silver nitrate. Some patients may benefit from having their teeth separated with nonconducting rubber dam material.

Analysis of Variance↗

PubMed1995

Metal content and conformation of the metalloprotease from the marine sponge Spheciospongia vesparia.

We have recently purified a protease from the marine sponge Spheciospongia vesparia. It consists of a single nonglycosylated polypeptide chain with a molecular weight of 29 600 and has one free thiol group. Metal analysis revealed the presence of zinc at 2.02 +/- 0.05 g-atoms per mole of protein, as measured by atomic absorption spectroscopy. The circular dichroism spectrum in the far UV region (183-259 nm) indicates that the sponge protease contains appreciable amounts of beta sheet. This enzyme resembles very much an aminopeptidase from Aeromonas proteolytica concerning activity and some physiochemical characteristics.

Aeromonas↗

PubMed2004

Diastereoselective additions of chiral vinylzinc reagents to alpha-chiral aldehydes.

[reaction: see text] Additions of vinylic zinc bromide reagents to alpha-chiral aldehydes (R(1) = CH(2)OTBS, R(2) = Me; R(1) = Me, R(2) = OTBS) in the presence of lithiated (+)- or (-)-N-methylephedrine proceed with predominant reagent control to afford anti or syn adducts stereoselectively, except when the aldehydes possess an alkoxy substituent at the alpha- or beta-positions (R(1) = Me, R(2) = OBn; R(1) = CH(2)OBn, R(2) = Me), in which case chelation-controlled adducts predominate.

Aldehydes↗

PubMed2007

Theoretical studies on farnesyltransferase: the distances paradox explained.

In spite of the enormous interest that has been devoted to its study, the mechanism of the enzyme farnesyltransferase (FTase) remains the subject of several crucial doubts. In this article, we shed a new light in one of the most fundamental dilemmas that characterize the mechanism of this puzzling enzyme commonly referred to as the "distances paradox", which arises from the existence of a large 8-A distance between the two reactive atoms in the reaction catalyzed by this enzyme: a Zn-bound cysteine sulphur atom from a peptidic substrate and the farnesyldiphosphate (FPP) carbon 1. This distance must be overcome for the reaction to occur. In this study, the two possible alternatives were evaluated by combining molecular mechanics (AMBER) and quantum chemical calculations (B3LYP). Basically, our results have shown that an activation of the Zn-bound cysteine thiolate with subsequent displacement from the zinc coordination sphere towards the FPP carbon 1 is not a realistic hypothesis of overcoming the large distance reported in the crystallographic structures of the ternary complexes between the two reactive atoms, but that a rotation involving the FPP molecule can bring the two atoms closer with moderate energetic cost, coherent with previous experimental data. This conclusion opens the door to an understanding of the chemical step in the farnesylation reaction.

Binding Sites↗

PubMed1983

Genotoxicity studies with a blend of zinc dialkyldithiophosphate lubricant additives.

The mutagenic activity of a blend of primary zinc dialkyldithiophosphate lubricant additives suspended in process oils and a blend of the process oils alone was investigated in agar layer cultures of Salmonella typhimurium TA1535, TA1537, TA1538, TA98 and TA100, both with and without the incorporation of a rat liver microsomal activation system (S9). Zinc dimethyldithiocarbamate was tested as a structurally-related model bacterial mutagen, and, in additional control experiments, the mutagenic activity of zinc dimethyldithiocarbamate and benzo[a]pyrene was investigated in combination with the blend of process oils in selected bacterial tester strains. Transformation frequencies of BHK cells were determined by colony growth in soft agar culture following treatment with a blend of the zinc dialkyldithiophosphate lubricant additives suspended in process oils, a blend of the process oils, 7,12-dimethylbenzanthracene, both in the presence and in the absence of a blend of the process oils, or zinc dimethyldithiocarbamate. All experiments incorporated a rat liver microsomal activation system (S9). Application of a blend of the zinc dialkyldithiophosphate additives or a blend of the process oils used in their manufacture did not increase the reverse mutation frequencies of Salmonella typhimurium TA1535, TA1537, TA1538, TA98 or TA100, or significantly increase the transformation frequency of BHK cells under the experimental conditions described. Zinc dimethyldithiocarbamate increased the reverse mutation frequency in some bacterial tester strains, but did not significantly increase the transformation frequency of BHK cells under the described experimental conditions. The addition of the blend of the process oils in combination with the control materials, zinc dimethyldithiocarbamate or benzo[a]pyrene had an inhibitory effect on the mutagenic activity at high doses of each in the bacterial assays, and in the BHK assay the transforming ability of 7,12-dimethylbenzanthracene was suppressed in the presence of the blend of the process oils. Thus, the additive materials showed no evidence of genotoxic activity in the bacterial mutation assays, or in the BHK transformation assay under the experimental conditions described.

Animals↗

PubMed1995

Rat thimet oligopeptidase: large-scale expression in Escherichia coli and characterization of the recombinant enzyme.

The coding sequence for rat testis thimet oligopeptidase (TOP) (EC 3.4.24.15) was placed under the control of the T7 polymerase/promoter system. Cultures of Escherichia coli transfected with the resulting plasmid expressed the enzyme as a soluble cytoplasmic protein. Medium-scale cultures allowed isolation of the enzyme in quantities of tens of milligrams. The availability of the recombinant enzyme permitted the determination of such chemical properties as epsilon 280 (48,960), zinc content (2 atom/molecule) and available thiol content (8-10/molecule) for TOP. The recombinant enzyme showed the catalytic activities previously reported for the naturally occurring enzyme, so that we can now conclude with confidence that these are all due to TOP and there is no need to postulate the existence of separate 'Pz-peptidase' or 'endo-oligopeptidase A' enzymes.

Alkylating Agents↗

PubMed1992

Retrograde tracing of zinc-containing neurons by selenide ions: a survey of seven selenium compounds.

The autometallographic retrograde tracing of zinc-containing neurons by intracerebral injection of sodium selenite (Na2SeO3), introduced by Danscher in 1982, has recently been described in more detail. Intracerebral injections of both sodium selenide (Na2Se) and sodium selenite (Na2SeO3) have been successfully used; however, sodium selenite had a rather toxic effect on the injected tissue. In the present study, we tested seven different selenium compounds to find the most suitable compound for retrograde tracing of zinc-positive pathways. Among the tested compounds, sodium selenide (Na2Se) caused insignificant necrosis within the injection site and was easily transported retrogradely when handled anaerobically. Sodium selenide is therefore recommended as the compound of choice.

Animals↗

PubMed2000

Crystal structures and magnetic properties of metal complexes bearing four nitronyl nitroxide moieties in the same coordination sphere.

Mononuclear transition metal complexes of the type [M(2,6-NITpy)2](ClO4)2 x solvent (2,6-NITpy = 2,6-bis-(3'-oxide-1'-oxyl-4',4',5',5'-tetramethylimidazolin-2'-yl)pyridine; M = Ni (1), Co (2), Zn (3), Mn (4), Cu (5)) have been synthesized and characterized by single-crystal X-ray diffraction studies. Crystal data: 1, monoclinic, P2(1)/c, Z = 4, a = 20.946(2) A, b = 12.0633(2) A, c = 21.173(2) A, beta = 113.55(1) degrees; 2, monoclinic, P2(1)/c, Z = 4, a = 20.902(2) A, b = 12.0981(8) A, c = 21.215(2) A, beta = 113.130(9) degrees; 3, triclinic, P1, Z = 2, a = 11.410(1) A, b = 12.932(1) A, c = 21.609(2) A, alpha = 96.040(2) degrees, beta = 102.24(1) degrees, gamma = 114.98(1); 4, monoclinic, P2(1)/n, Z = 4, a = 11.5473(8) A, b = 19.212(1) A, c = 25.236(2) A, beta = 98.772(9) degrees; 5, triclinic, P1, Z = 2, a = 12.1604(9) A, b = 12.6961(9) A, c = 18.103(2) A, alpha = 84.191(8) degrees, beta = 73.392(8) degrees, gamma = 66.072(8). The two 2,6-NITpy biradicals behave as terdentate ligands and bind almost perpendicular to each other in meridional positions. In compounds 1-4, the pyridine rings are axially ligated and four different nitronyl nitroxide radicals bind to the metal center through their O(nitroxyl) atoms, forming the equatorial plane of a distorted octahedron. On the contrary, in the copper(II) complex (5), the two N(pyridyl) atoms are found in equatorial positions. Only two nitroxide groups are then bound to the copper(II) ion in the equatorial plane, the other two being axially ligated. The two axially bound nitronyl nitroxide radicals couple ferromagnetically to the copper center (JCu-rad(ax) = + 10 K), whereas a strong antiferromagnetic coupling between this metal ion and the equatorial nitroxide groups (JCu-rad(eq) = -460 K) is observed. The other complexes exhibit strong antiferromagnetic metal-radical interactions: JNi-rad = -240 K, for 1; JMn-rad = -120 K, for 4. Interestingly, the study of the diamagnetic zinc(II) compound (3) reveals a moderate intramolecular antiferromagnetic interaction between radicals coordinated to the same metal center (Jrad-rad = -27.7 K). This interaction is transmitted through space and is also present in the other complexes: Jrad-rad = -14 K, for 1; Jrad-rad = -10 K, for 4; Jrad-rad = -20.5 K, for 5. Antiferromagnetic intermolecular interactions are also present in all the complexes herein studied.

Journal Article↗

PubMed2002

Intracellular distribution of labile Zn(II) and zinc transporter expression in kidney and MDCK cells.

Kidneys play a key role in zinc balance. The portion of Zn(II) that enters the glomerular filtrate is efficiently reabsorbed along the nephron through a mechanism yet to be identified. We used the Zn(II)-specific fluorophore Zinquin to visualize intracellular Zn(II) accumulated in the kidney epithelium and compared it with the intracellular localization of the vesicular zinc transporter ZnT4 both in vivo and in vitro. The Madin-Darby canine kidney (MDCK) cell line, stably overexpressing rat ZnT4, was used as a tissue culture model of the kidney epithelium. Zinquin labeling of MDCK cells revealed rapid internalization of Zn(II) and compartmentalization in intracellular bodies interspersed throughout the cytoplasm. In polarized kidney cells, ZnT4 protein was localized on the membrane of intracellular vesicles concentrated around the nucleus, mostly on the basal side. Results of double stainings demonstrated that ZnT4-containing vesicles do not overlap with Zn(II) bodies. Zinquin fluorescence, confirmed by autometallography in rat kidney, indicated that consistent with its physiological role, the central glomerulus was weakly stained, whereas the epithelium that lines convoluted tubules was strongly labeled. Double staining of rat kidney with Zinquin and anti-ZnT4 antibodies confirmed the in vitro observations, as Zinquin fluorescence appeared to be distinct from ZnT4 immunofluorescence. To gain further insight into which of the known zinc transporters might be involved in Zn(II) metabolism in the kidney, we have also characterized by RT-PCR the expression of other proteins involved in Zn(II) transport. All of the mRNAs examined [ZnT1, -T2, -T4, and human Zrt, Irt-like protein 1 (hZIP1)], with the exception of hZIP2, were present in adult rat kidney.

Animals↗

PubMed2006

A novel regulatory metal binding domain is present in the C terminus of Arabidopsis Zn2+-ATPase HMA2.

HMA2 is a Zn2+-ATPase from Arabidopsis thaliana. It contributes to the maintenance of metal homeostasis in cells by driving Zn2+ efflux. Distinct from P1B-type ATPases, plant Zn2+-ATPases have long C-terminal sequences rich in Cys and His. Removal of the 244 amino acid C terminus of HMA2 leads to a 43% reduction in enzyme turnover without significant effect on the Zn2+ K(1/2) for enzyme activation. Characterization of the isolated HMA2 C terminus showed that this fragment binds three Zn2+ with high affinity (Kd = 16 +/- 3 nM). Circular dichroism spectral analysis indicated the presence of 8% alpha-helix, 45% beta-sheet, and 48% random coil in the C-terminal peptide with noticeable structural changes upon metal binding (8% alpha-helix, 39% beta-sheet, and 52% random coil). Zn K-edge XAS of Zn-C-MBD in the presence of one equivalent of Zn2+ shows that the average zinc complex formed is composed of three His and one Cys residues. Upon the addition of two extra Zn2+ ions per C-MBD, these appear coordinated primarily by His residues thus, suggesting that the three Zn2+ binding domains might not be identical. Modification of His residues with diethyl pyrocarbonate completely inhibited Zn2+ binding to the C terminus, pointing out the importance of His residues in Zn2+ coordination. In contrast, alkylation of Cys with iodoacetic acid did not prevent Zn2+ binding to the HMA2 C terminus. Zn K-edge XAS of the Cys-alkylated protein was consistent with (N/O)4 coordination of the zinc site, with three of those ligands fitting for His residues. In summary, plant Zn2+-ATPases contain novel metal binding domains in their cytoplasmic C terminus. Structurally distinct from the well characterized N-terminal metal binding domains present in most P1B-type ATPases, they also appear to regulate enzyme turnover rate.

Absorptiometry, Photon↗