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Kinetic analysis and comparison of uptake, distribution, and excretion of 48V-labeled compounds in rats.

Vanadium has been found to be orally active in lowering plasma glucose levels; thus it provides a potential treatment for diabetes mellitus. Bis(maltolato)oxovanadium(IV) (BMOV) is a well-characterized organovanadium compound that has been shown in preliminary studies to have a potentially useful absorption profile. Tissue distributions of BMOV compared with those of vanadyl sulfate (VS) were studied in Wistar rats by using 48V as a tracer. In this study, the compounds were administered in carrier-added forms by either oral gavage or intraperitoneal injection. Data analyzed by a compartmental model, by using simulation, analysis, and modeling (i.e., SAAM II) software, showed a pattern of increased tissue uptake with use of 48V-BMOV compared with 48VS. The highest 48V concentrations at 24 h after gavage were in bone, followed by kidney and liver. Most ingested 48V was eliminated unabsorbed by fecal excretion. On average, 48V concentrations in bone, kidney, and liver 24 h after oral administration of 48V-BMOV were two to three times higher than those of 48VS, which is consistent with the increased glucose-lowering potency of BMOV in acute glucose lowering compared with VS.

Animals↗

Refinement of solid-state MAS NMR spectra of quadrupolar nuclei: application to the analysis of some 51V compounds.

Magic angle solid-state 51V NMR spectra of several vanadium powder compounds have been recorded. A refinement of these spectra using theoretical simulations of the powder spectra have been performed assuming the simultaneous anisotropic effects of electric field gradients (EFG) and of electronic shielding. It is shown that the relative orientation of the principal axes of the two tensors have to be considered.

Anisotropy↗

Isolation, properties and structural studies on a compound from tunicate blood cells that may be involved in vanadium accumulation.

A novel compound, for which the trivial name tunichrome is proposed, was isolated from the vanadium-rich blood cells of the tunicate Ascidia niga. Preliminary structural studies suggest a molecular weight of about 390, the presence of conjugated vinyl groups, and an acidic group, possibly carboxyl, with an apparent pKa of 3.0. Elements C, H, N and O comprise 98.4% of the sample weight, the number of atoms per mol of tunichrome being 14.1, 22.2, 1.5 and 10.6 respectively, which indicates some heterogeneity in the sample. Tunichrome readily reduces Fe(III) and V(V). In an initial fast step, 2 mol of V(V) are reduced, or 4 mol of Fe(III)-phenanthroline per mol of tunichrome; in a further slow reaction, another 9 mol of Fe(III)-phenanthroline or Fe(III)-bipyridine are reduced. The initial reaction is first-order with respect to tunichrome and Fe(III). Above pH 3.5, tunichrome is rapidly hydrolysed, 13 mol of OH- being consumed per mol of tunichrome. The hydrolysis involves polymerization and loss of the characteristic absorption peak at 325 nm. It is suggested that the presence of tunichrome may be linked to vanadium accumulation by the blood cells. The mechanism involves entry of vanadate via an anionic channel into vacuoles of the blood cells, where it is reduced to V(IV) or V(III), both of which, being cationic, cannot escape from the vacuole.

Animals↗

Anti-RNA virus activity of polyoxometalates.

The anti-RNA virus activity of polyoxometalates (POM) is reviewed, with a special emphasis on the anti-respiratory virus activities. There are many causative agents of acute viral respiratory infections; and it is rather difficult to identify the relevant agent in a given case by rapid clinical means. During acute progress of infection before the definitive diagnosis is obtained physicians need to prescribe certain broad spectrum anti-viral drugs. A titanium containing polyoxotungstate, PM-523 exhibited potent anti-influenza virus (FluV) A and anti-respiratory syncytial virus (RSV) activities in vitro. Therapeutic effect of FluV A infected mice with aerosol inhalation of PM-523 was proven. A vanadium substituted polyoxotungstate, PM-1001 has antiviral activity against FluV A, RSV, parainfluenza virus (PfluV) type 2, Dengue fiver virus, HIV-1 and SARS coronavirus in vitro. Thus, POMs have been proven to be broad spectrum and non-toxic anti-RNA virus agents in both in vitro and in vivo experiments and are promising candidates for first-line therapeutics in acute respiratory diseases.

Animals↗

[Catalytic performance of a novel ceramic-supported vanadium oxide catalyst for NO reduction with NH3].

A novel TiO2/Al2O3/ceramic cordierite honeycomb (CC)-supported V2O5-MoO3-WO3 monolithic catalyst was studied for the selective reduction of NO with NH3. The effects of reaction temperature, space velocity, NH3/NO ratio and oxygen content on selective catalytic reduction (SCR) activity were evaluated. Two other V2O5-MoO3-WO3 monolithic catalysts supported on Al2O3/CC or TiO2/CC support, two types of pellet catalysts supported on TiO2/Al2O3 or Al2O3, as well as three types of pellet catalysts V2O5-MoO3-WO3-Al2O3 and V2O5-MoO3-WO3-TiO2 were tested for comparison. The experiment results showed that this catalyst had a higher catalytic activity for SCR with comparison to others. The results of characterization showed, the preparation method of this catalyst can give rise to a higher Brunauer, Emmett, Teller (BET) surface area and pore volume, which was strongly related with the highly active performance of this catalyst. At the same time, the function of the combined carrier of TiO2/Al2O3 cannot be excluded.

Air Pollutants↗

Characterization of a spontaneous mutant of Azotobacter vinelandii in which vanadium-dependent nitrogen fixation is not inhibited by molybdenum.

A spontaneous mutant derivative of Azotobacter vinelandii CA12 (delta nif HDK), which vanadium-dependent nitrogen fixation is not inhibited by molybdenum (A. vinelandii CARR), grows profusely on BNF-agar containing 1 microM Na2MoO4, alone or supplemented with 1 microM V2O5. The expression of A. vinelandii vnfH::lacZ and vnfA::lacZ fusions in A. vinelandii CARR was not inhibited by 1 mM Na2MoO4, whereas molybdenum at much lower concentration inhibited the expression of vnfH::lacZ and vnfA::lacZ fusions in A. vinlandii CA12. The mutant also exhibited normal acetylene reduction activity in the presence of 1 microM Na2MoO4. The expression of A. vinelandii nifH::lacZ fusion in A. vinelandii CARR was low even though the cells were cultured under non-repressing conditions with urea as nitrogen source in the presence of Na2MoO4. The molybdenum content of A. vinelandii CARR cells was found to be about one-fourth that of A. vinelandii CA12. No nitrate reductase activity could be detected in A. vinelandii CARR when the cells were cultured in the presence of 10 microM Na2MoO4, whereas A. vinelandii CA12 exhibited some activity even with 100 pM Na2MoO4.

Acetylene↗

In vitro cell growth inhibition by metallocene dichlorides.

The in vitro growth-inhibiting potencies of titanocene dichloride (TDC), zirconocene dichloride (ZDC), hafnocene dichloride (HDC), vanadocene dichloride (VDC), and molybdocene dichloride (MDC) against Ehrlich ascites tumor (EAT) cells cultured in viro as permanently growing suspension cultures were determined. The most striking growth-suppression activity was detected for VDC. A VDC concentration as low as 5. 10(-6) mol/l effects a highly significant diminution of cell proliferation. TDC and MDC inhibit cellular growth only concentration of 5 . 10(-4) or 10(-3) mol/l, respectively, whereas ZDC and HDC, which are ineffective against EAT cells in vivo, require higher concentration levels. The growth inhibition is caused by a cytotoxic action of the metallocene dichlorides, as is demonstrated in the case of VDC and TDC by differentiation of live and dead EAT cells by means of the dye lissamine green.

Animals↗

Insulin-like vs. non-insulin-like stimulation of glucose metabolism by vanadium, tungsten, and selenium compounds in rat muscle.

The direct impact of vanadate, tungstate, selenate, and selenite on glucose metabolism of isolated rat soleus muscle was investigated. All compounds stimulated glucose transport, but only vanadate exerted an insulin-like effect on glycogen synthesis (mumol glucose into glycogen*g-1*h-1: control 1.43 +/- 0.11 vs. 1 mmol/l vanadate, 2.08 +/- 0.11, p < 0.0001), which was more distinct in the presence of 1 mmol/l H2O2 (control, 1.44 +/- 0.13 vs. 1 mmol/l vanadate, 3.49 +/- 0.12, p < 0.001). Glucose handling of muscles exposed to tungstate, selenate, or selenite resembled that of hypoxic muscle, i.e. the induced rise in glucose uptake was inhibited by dantrolene and associated with high rates of glycolysis and rapid glycogen depletion (glycogen content after incubation, mumol glucosyl units/g: control, 16.2 +/- 0.7 vs. hypoxia, 2.7 +/- 0.5, p < 0.0001; control, 17.0 +/- 0.5 vs. 100 mmol/l tungstate, 5.5 +/- 0.4, p < 0.001; control, 16.2 +/- 0.7 vs. 100 mmol/l selenate, 1.5 +/- 0.3, and vs. 300 mumol/l selenite, 1.7 +/- 0.3, p < 0.0001 each). The results suggest that vanadate (and more pronounced it's peroxides) exerts true insulin-like action on isolated muscle glucose metabolism, whereas tungsten and selenium salts trigger glucose transport in association with a catabolic response, which may represent an unspecific response to toxic/osmotic stress.

Androstadienes↗

Oxygen Abstraction Reactions of N-Substituted Hydroxamic Acids with Molybdenum(V) and Vanadium(III) and -(IV) Compounds.

A wide range of N-substituted mono- and dihydroxamic acids undergo oxygen abstraction on reaction with V(III), V(IV), and Mo(V) compounds to form hydroxamates of V(V) and Mo(VI) respectively together with the corresponding amides and diamides. The molybdenyl and vanadyl hydroxamates form metal-oxygen clusters under FABMS conditions. The X-ray crystal structures of [MoO(2){CH(3)(CH(2))(n)()C(O)N(C(6)H(5))O}(2) (1 and 2) (n = 4, 5) show monomeric structures with structural trans effects and consequent weakening of the Mo-O(ligand) bonds which may account for the tendency to form clusters in FABMS. In constrast, the electrospray MS of the vanadyl dihydroxamates, VO(OH)[PhN(O)C(O)(CH(2))(n)()C(O)N(O)Ph] (n = 3, 5) and VO(OH)[p-CH(3)C(6)H(4)N(O)C(O) (CH(2))(n)()C(O)N(O)C(6)H(4)-CH(3)) (n = 2, 4) show the presence of dimers in solution.

Journal Article↗

Arsenite exposure of cultured airway epithelial cells activates kappaB-dependent interleukin-8 gene expression in the absence of nuclear factor-kappaB nuclear translocation.

Airway epithelial cells respond to certain environmental stresses by mounting a proinflammatory response, which is characterized by enhanced synthesis and release of the neutrophil chemotactic and activating factor interleukin-8 (IL-8). IL-8 expression is regulated at the transcriptional level in part by the transcription factor nuclear factor (NF)-kappaB. We compared intracellular signaling mediating IL-8 gene expression in bronchial epithelial cells cultured in vitro and exposed to two inducers of cellular stress, sodium arsenite (As(III)), and vanadyl sulfate (V(IV)). Unstimulated bronchial epithelial cells expressed IL-8, and exposure to both metal compounds significantly enhanced IL-8 expression. Overexpression of a dominant negative inhibitor of NF-kappaB depressed both basal and metal-induced IL-8 expression. Low levels of nuclear NF-kappaB were constitutively present in unstimulated cultures. These levels were augmented by exposure to V(IV), but not As(III). Accordingly, V(IV) induced IkappaBalpha breakdown and NF-kappaB nuclear translocation, whereas As(III) did not. However, both As(III) and V(IV) enhanced kappaB-dependent transcription. In addition, As(III) activation of an IL-8 promoter-reporter construct was partially kappaB-dependent. These data suggested that As(III) enhanced IL-8 gene transcription independently of IkappaB breakdown and nuclear translocation of NF-kappaB in part by enhancing transcription mediated by low levels of constitutive nuclear NF-kappaB.

Arsenites↗

Effects of bis(maltolato)oxovanadium(IV) are distinct from food restriction in STZ-diabetic rats.

In association with the insulin-mimetic properties, vanadium and related compounds have been shown to normalize hyperphagia associated with diabetes mellitus. The objective of this study was to clarify the effects of an organic vanadium compound, bis(maltolato)oxovanadium(IV) (BMOV), vs. food restriction on the metabolic abnormalities that occur in diabetes. BMOV was administered daily in drinking water to streptozotocin (STZ)-diabetic rats for 6 wk. Pair-fed groups were fed based on the intake for their respective counterparts from the previous day. Plasma parameters were measured weekly after a carefully controlled 5-h fasting period. BMOV reduced plasma glucose (diabetic = 31.2 +/- 1.9, diabetic treated = 10.2 +/- 1.8, and diabetic pair fed = 34.2 +/- 1.1 mM), triglyceride, and cholesterol levels to normal without a concomitant increase in plasma insulin levels. There was no body weight gain in the diabetic pair-fed group compared with all other groups. BMOV but not pair feeding was effective in preventing the decreased cardiac function observed in STZ-diabetic rats. These data suggest that the glucose-lowering properties of BMOV are independent of the effects of dietary restriction and reinforce the efficacy of BMOV as an effective antihyperglycemic agent.

Animals↗

Vanadyl(IV) complexes with saccharides. Bioactivity in osteoblast-like cells in culture.

Complexes of vanadyl(IV) with 4 monosaccharides and 5 disaccharides were tested in 2 osteoblast-like cell lines (MC3T3E1 and UMR106). Many complexes caused stimulation of UMR106 proliferation (120% basal) in the range of 2.5 to 25 micromol/L. In the nontransformed osteoblasts, some vanadyl-saccharide complexes stimulated the mitogenesis (115% basal) in the same range of concentration. The glucose and sucrose complexes were the most efficient inhibitory agents (65% and 88% of inhibition vs. basal, respectively) for tumoral cells at 100 micromol/L. The galactose and turanose complexes exerted a similar effect in the nontransformed osteoblasts. On the other hand, all the complexes promoted the phosphorylation of the extracellular regulated kinases (ERKs). All together, these results indicate that the stimulation of ERKs is not the only factor that plays a role in the proliferative effects of vanadium derivatives since some compounds were inhibitory proliferating agents. Cell differentiation was evaluated by alkaline phosphatase specific activity and collagen synthesis in UMR106 cells. All the complexes inhibited alkaline phosphatase activity, with galactose complex as the most effective compound (IC50 = 43 micromol/L). The complex with the trehalose TreVO was the most effective agent to stimulate collagen synthesis (142% basal) and glucose consumption (132% basal). A cytosolic tyrosine protein kinase and the kinase-3 of glycogen synthase seem to be involved in the stimulation of glucose consumption by vanadium derivatives. In this series, only TreVO gathered the characteristics of a good insulin mimetic and osteogenic drug. In addition, this complex was a good promoting agent of nontransformed osteoblast proliferation, whereas it inhibited tumoral osteoblasts. GluVO, the complex with glucose, was also more toxic for tumoral than for nontransformed cells. These 2 vanadium derivatives are good potential antitumoral drugs. All the results suggest that the biological effects of vanadium compounds are a complex phenomenon influenced by the complexation, the dose, and the nature of the ligands and the cells.

3T3 Cells↗

[Raw material synthesis and characterization of YVO4 birefringent crystal].

In this paper, synthesis of YOV4 birefringence crystal raw material in liquid phase was studied. Mostly, the effects of solution's pH values and some other synthesis conditions on purity and whiteness were discussed. Infra-red spectrometry, X-ray powder diffraction and UV spectrometry were used in the characterization of the raw material and single crystal, and in this way the best method of synthesis was defined. The result of the study indicates that the purity of the raw material had decisive effect on the crystal growth. Flawless crystal with the dimensions of phi 40 x 40 x 50 mm3 was grown by Czochralski (CZ) technique.

Birefringence↗

Solid state and solution studies of a vanadium(III)-L-cysteine compound and demonstration of its antimetastatic, antioxidant and inhibition of neutral endopeptidase activities.

Reaction of one equivalent of vanadium(III) chloride with three equivalents of l-cysteine(H2Cys) in methyl alcohol affords a VIII-Cys compound that is formulated as [VIII(Hcys)3].2HCl.2.5H2O 1. The solid state characterization of 1 was performed by microanalysis, circular dichroism (CD) and infrared studies as well as room temperature magnetic susceptibility. These studies have shown coordination of each HCys- ligand to the VIII atom through an amine nitrogen and a carboxylate oxygen atoms. Solution studies of 1 were carried out in water and methanol by UV-visible, CD and electron paramagnetic resonance (EPR) spectroscopies. According to these studies, it was evident that despite the progressive oxidation of 1 to oxovanadium(IV) species, some V(III) species were also present in solution after several hours. Compound 1, VIVOSO4.5H2O and l-cysteine were examined for their total antioxidant capacity (TAC) and lag time. Compound 1 exhibited significantly greater total antioxidant capacity and lag time values than l-cysteine. VIVOSO4.5H2O did not show any total antioxidant capacity or lag time. The inhibition of neutral endopeptidase (NEP) activity caused by 1, VIVOSO4.5H2O and thiorphan was also measured. Compound 1, at a concentration of 10(-3) M, showed inhibition of NEP activity as potent as thiorphan at 10(-6) M, while VIVOSO4.5H2O in the same concentration exhibited less than 50% inhibitory activity than that of thiorphan at 10(-6) M. Moreover, the antimetastatic effects of compound 1, l-cysteine and VIVOSO4.5H2O were examined on Wistar rats, treated with 3,4-benzopyrene. The results revealed that 1 prevents significantly lung metastases (only 9.5% of animals treated with 1 showed metastases), whereas 47-52% of the rats of the control group and those treated with l-cysteine and VIVOSO4.5H2O exhibited metastases.

Animals↗