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Vanadium induced impairment of haem synthesis.

Biochemical and haematological profiles of workers exposed to vanadium were compared with those of non-exposed age matched subjects. A significantly positive and dose related correlation between serum vanadium and zinc protoporphyrin (ZPP) was observed. Normal lead concentrations excluded this heavy metal as a possible cause. Inhibition of the reduction of Fe to Fe++ by vanadium is discussed as the possible cause of interference of vanadium with haem synthesis. Iron and iron binding capacity were found to be significantly lower and ferritin significantly higher in the population exposed to vanadium. Strong inter-individual variations do not allow an explanation of this interference with iron metabolism.

Heme↗

Vanadium and the cardiovascular functions.

Inorganic and organic compounds of vanadium have been shown to exhibit a large range of insulinomimetic effects in the cardiovascular system, including stimulation of glucose transporter 4 (GLUT-4) translocation and glucose transport in adult cardiomyocytes. Furthermore, administration of vanadium compounds improves cardiac performance and smooth muscle contractility, and modulates blood pressure in various models of hypertension and insulin resistance. Vanadium compounds are potent inhibitors of protein tyrosine phosphatases. As a result, they promote an increase in protein tyrosine phosphorylation of several key components of the insulin signaling pathway, leading to the upregulation of phosphatidylinositol 3-kinase and protein kinase B, two enzymes involved in mediating GLUT-4 trans location and glucose transport. In addition, vanadium has also been shown to activate p38 mitogen-activated protein kinase and increase Ca2+ levels in several cell types. The ability of vanadium compounds to activate these signaling events may be responsible for their ability to modulate cardiovascular functions.

Animals↗

Vanadium, Na-K-ATPase, and potassium adaptation in the rat.

Vanadate is a potent inhibitor of Na-K-ATPase in vitro. It has been suggested that vanadium may function as a cellular regulator of Na-K-ATPase in vivo. To examine this speculation, we studied in rats the effect of high vanadate intake on 1) the tissue levels and distribution of vanadium, 2) basal activity of Na-K-ATPase in various tissues, and 3) the activity of Na-K-ATPase in various organs under conditions of massive chronic potassium loading known to stimulate Na-K-ATPase in the kidney and colon. Despite extremely high tissue levels of vanadium there was no demonstrable effect of the element on the basal activity of Na-K-ATPase. When subjected to chronic potassium loading, rats with high tissue vanadium concentrations underwent potassium adaptation that was associated with a rise in Na-K-ATPase activity in the renal cortex, renal medulla, and colonic mucosa. Further studies are needed to support or refute the thesis that vanadium might be an intracellular regulator of Na-K-ATPase in vivo.

Animals↗

Serum vanadium levels in chronic hemodialysis patients.

Serum vanadium, aluminum, silicon and beta 2-microglobulin levels as well as the red cell count, hemoglobin and systolic blood pressure were simultaneously measured in 80 chronic hemodialysis patients. The serum vanadium level was positively correlated with the serum levels of aluminum, silicon and beta 2-microglobulin as well as the systolic blood pressure, and was inversely correlated with the red cell count and hemoglobin. The mean serum vanadium level was 18.4 +/- 7.6 ng/ml before hemodialysis and decreased to 13.0 +/- 5.30 ng/ml at the completion of dialysis. The dialysate vanadium level increased from 0.4 +/- 0.2 (inflow) to 1.0 +/- 0.4 ng/ml (outflow). It was concluded that vanadium was transferred from blood to dialysate when purified water was used in the preparation of the dialysate.

Aged↗

Inhaled vanadium pentoxide decrease gamma-tubulin of mouse testes at different exposure times.

Vanadium is an important environmental and industrial pollutant whose concentrations have increased in the last decades. Due to its status as reproductive toxicant and a microtubule damaging agent, the present study investigated by immunohistochemistry the effect of the inhalation of vanadium pentoxide on gamma-tubulin within somatic and testicular germ cells. Male mice inhaled vanadium pentoxide (V2O5) (0.02 M) 1 h/twice a week for 12 weeks. Our results demonstrated that vanadium accumulates in the testes starting with the initial inhalation (24 h), and this pattern remained until the last week of treatment. In general, vanadium was capable of significantly decreasing the percentage of gamma-tubulin in all analyzed testicular cells (Sertoli, Leydig and germ cells) starting with the first week of treatment. For all cell types studied, regression analysis revealed a negative and significant relationship between the percentage of immunopositive cells to gamma-tubulin and exposure time, showing a time dependent response in all cases. Our findings suggest that alterations on this protein might imply changes in microtubule-involved function such as cell division, which in the testes might lead to damage in the spermatogenesis, leading probably to infertility.

Administration, Inhalation↗

Channeling of vanadium in two species of fungi.

Aspergillus flavus and Penicillium italicum were cultivated on Dox medium amended with different concentrations of a vanadium salt; vanadium pentoxide (V2O5). The fungal isolates were found to absorb considerable quantities of vanadium. Fungal contents of carbohydrates and proteins were decreased by the presence of vanadium in the growth environment. Vanadium was incorporated into several types of low and high molecular weight protein(s) and peptides. In case of P. italicum, lysine, tyrosine, glycine, methionine, valine, alanine, proline, glutamic acid and histidine were detected in the fungal cell free extract. While in case of A. flavus, the following amino acids were detected: cystine, methionine, leucine, phenylalanine, glycine, alanine, tyrosine, lysine, histidine, arginine and valine.

Amino Acids↗

Determination of vanadium accumulation in onion root cells (Allium cepa L.) and its correlation with toxicity.

The vanadium is a metal that presents great interest from the toxicological point of view, because of the numerous alterations that can take place in different biological systems. This work evaluated the capacity of vanadium accumulation and its correlation with genotoxic effects in root cells of Allium cepa L. The bulbs were cultivated in renovated filtered water each 24 h, at a temperature of 25 +/- 0.5 degrees C, in darkness and constant aeration. Treatments were carried out under the same experimental conditions, using water solutions of vanadium of 25, 50, 75 and 100 microg/g for 0, 12, 24, 48 and 72 h. A control was carried out where metal solution was substituted by distilled water. After the treatment, the meristems were fixed with alcohol--acetic acid (3:1) and stained according to the technique of Feulgen. The capacity of accumulation was determined by GFAAS. The analysis of the results revealed an accumulation of the metal for all times and concentrations. No correlation was presented among vanadium accumulation, growth and mitotic index; however, positive correlation was given with the induction of chromosomic aberrations. In conclusion, vanadium is able to induce cytotoxic effect in the exposed roots, but only genotoxic effect was correlated with metal accumulation.

Analysis of Variance↗

[Acute exposure to vanadium-containing dusts: the health effects and biological monitoring in a group of workers employed in boiler maintenance].

The authors describe an episode of acute intoxication due to inhalation of vanadium-containing dusts in a group of 10 workers during maintenance work inside a boiler of an oil-fired electricity power station. Historical, clinical and biological monitoring data concerning the acute exposure phase and subsequent checks are presented. The appearance of irritative symptoms of the upper airways, green tongue (in 6 out of 10 subjects) and the values of urinary excretion of vanadium (means = 92, D.S. = 47 micrograms/l: limits 20-270 micrograms/l) indicated acute vanadium exposure. With the use of appropriate individual protection devices and shorter shifts, 2 weeks after the episode there was a complete remission of the symptoms and a return of urinary vanadium concentrations to 38, D.S. = 26 micrograms/l. Checks made 6 months, 1 and 2 years later did not reveal any alterations in the general blood chemistry parameters and the urinary vanadium concentrations were below 1 microgram/l (reference value). As already often reported in the literature, this episode confirms the danger involved in working in the presence of fuel oil residues or ashes and the need to adopt appropriate prevention measures.

Acute Disease↗

Structure and function of vanadium-containing bromoperoxidases.

The properties of the vanadium-containing bromoperoxidases from the seaweeds Ascophyllum nodosum, Laminaria saccharina and the lichen Xanthoria parietina were studied. Upon reduction with sodium dithionite, these bromoperoxidases show EPR spectra which are typical of a vanadyl cation (VO2+). From the spectral parameters and a comparison with inorganic vanadyl complexes, we conclude that the ligand environment largely consists of oxygen donors. The data also show that the structure of the active sites in these enzymes is very similar. Since EPR spectra of vanadium(IV) bromoperoxidase are only obtained after reduction, the metal ion is present in the native enzymes in the 5+ oxidation state. All these enzymes loose their enzymic activity upon dialysis against citrate-phosphate (PO4(3-)) buffer at pH 3.8, containing EDTA. The brominating activity could be reconstituted by the addition of vanadate (VO4(3-)). The experiments suggest that vanadate is incorporated into these enzymes. In line with the EPR data, we propose a structure of the active site in which at least 4 oxygen atoms are present as donors for the central vanadium(V) ion. Since several inorganic peroxovanadium(V) complexes have been described, we suggest that the vanadium ion in bromoperoxidases serves as a binding site for H2O2. Upon subsequent binding of bromide this ion is oxidized by the peroxo-intermediate to form hypobromite. This model does not require valence state changes of the metal ion itself and indeed no changes in the EPR spectrum of reduced bromoperoxidase are observed upon addition of H2O2 or Br-. Further, bromoperoxidase reduced with a small excess of sodium dithionite is not active in the bromination reaction. The bromoperoxidases from the various sources show similarity in the amino-acid composition with a predominance of acidic amino acids. Distinct pH optima are observed in the bromination reaction catalysed by the bromoperoxidases. Despite the presence of the same prosthetic group in these enzymes with comparable vanadium ligand-field environment, the enzymic properties are very different. The specific activity as well as the Km for bromide differ greatly. Unlike the enzymes from the seaweeds A. nodosum and L. saccharina the bromoperoxidase from the lichen X. parietina is inhibited by low concentrations (1-5 mM) of nitrate. These bromoperoxidases have a remarkable resistance towards organic solvents such as methanol, ethanol and propanol.

Amino Acids↗

Vanadium--toxicity, metabolism, carrier state.

By using the method of radioactive isotopes on albino rats, we studied the rate and degree of absorption of vanadium in to the blood, the time of its retention in the organs and the kinetics of its excretion, the influence of stable vanadium on the generative function and the correlation between the carrier state in workers who are in contact with vanadium in its production and the levels of exposure. Varying rates of absorption in to the blood in dependence on the route of administration, accumulation of vanadium in the kidneys, bone tissue, liver, lungs, placenta, testicles and the mammary gland, predominant elimination by the kidneys during the first two days, the gonodotoxic and embryotoxic effects were established. Correlation was revealed between the content of vanadium in the urine of workers and the levels of exposure.

Animals↗

Vanadium air pollution: a cause of malabsorption and immunosuppression in cattle.

An epidemiological investigation into an "illthrift" problem occurring on a dairy farm adjacent to an alloy-processing unit, established that the probable cause of the problem was chronic vanadium poisoning. The disease manifested initially in animals 4-18 months old which showed emaciation, chronic diarrhoea and, in some cases, rhinitis, conjunctivitis and recumbency followed by death. Post-mortem (n = 17) and clinical-pathology findings (n = 60) indicated that malabsorption and immunosuppression were the basis of the pathogenesis in affected animals. Eight months after the commencement of the investigation, adult cows began showing evidence of emaciation, reduced milk production and an apparent increase in the number of abortions, stillbirths and dystocias. Over a 2-year period, 134 surface-soil samples, 134 subsoil samples and 134 grass samples from the farm were analysed for various fractions of vanadium. Thirty-four of each of these samples were collected at different time intervals (autumn 1990, summer 1991 and winter 1991) and at varying distances and directions from the processing unit, in order to gauge the magnitude of the problem, and the distribution pattern of vanadium, and to identify possible seasonal trends. The remaining 100 of each of these samples were taken at 100-m intervals over an area of approximately 1,140,000 m2 directly adjacent to the processing unit so that concentration isolines for vanadium could be drawn and the source more conclusively identified. The levels of vanadium were found to be highest closest to the mine, and surface-soil levels were consistently higher than subsoil levels, suggesting aerial pollution, which was confirmed by air sampling.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants↗

[An experimental study of the atherogenic effect of vanadium in body uptake with drinking water].

During one year toxicological experiment on white male rats, receiving orally vanadium in doses 0.005 mg/kg, equivalent to the accepted in Bulgaria norm for ist category surface waters and 0.01 mg/kg, equivalent to the actually met in the drinking waters of some regions in this country heightened concentrations, its atherogenic effect is studied by indices: total cholesterol, beta-lipoproteins, phospholipid, lecithin, total lipids, total proteins, and hexoses of glycoprotein in blood serum; hydroxyproline, hexosamines, hexauronic acids and hexoses, connected with the proteins, in the aorta. A methodic approach is used for studying the atherogenic effect of vanadium on the processes of natural aging of the cardiovascular system. It is established that at chronic oral effect of the studied doses of vanadium no changes occur in the biochemical component of the connective tissue of the aorta and there are no infringements of the blood metabolism. In relation to the lipidic-only a decrease in the total cholesterol in the serum is established. The results show, that during the experiment vanadium causes no acceleration in the processes of natural aging of the blood vessels and has no atherogenic effect. Comparing the data for vanadium concentration in the drinking of Bulgaria to our results give grounds to reckon, that its heightened content in drinking waters of some regions presents no risk factor for the development of atherosclerosis.

Animals↗

Metabolic problems in northeastern Thailand: possible role of vanadium.

Common metabolic problems in northeastern Thailand include renal stone disease, distal renal tubular acidosis, hypokalemic periodic paralysis, sudden unexplained nocturnal death and malnutrition-related diabetes mellitus. There is evidence of decreased activity of Na,K-ATPase and H,K-ATPase. A preliminary study was made of the vanadium concentration in the soil and water in northeastern Thailand. The urinary and tissue vanadium concentrations were also determined in the northeastern villagers. The soil was found to have high vanadium content. The vanadium content was also high in the urine, kidneys and lungs of the villagers. It is postulated that these metabolic problems are attributed to the inhibition of Na,K-ATPase and H,K-ATPase activity by vanadium.

Humans↗

Distribution of titanium and vanadium following repeated injection of high-dose salts.

Titanium and its alloy of 6% aluminium and 4% vanadium are used extensively in orthopedic and dental surgery. However, in conditions of motion leading to wear, there is significant generation of wear products with deposition of black debris in the tissue. The questions remain as to how much of this debris is generated and to where it is transported. Previous studies have been hampered by low levels of detected elements giving values just above the background levels found in normal tissue and body fluids. The purpose of these experiments was to increase the body burden of titanium and vanadium by injecting larger doses of titanium and vanadium salts over an extended period of time. Each animal (Syrian hamster) received 100 micrograms of each element once a week for six weeks. The hamster was sacrificed on the seventh week and body fluids and tissue harvested. The results indicate that in the experimental animals there was transport of vanadium with levels above control in urine, plasma, liver, spleen, and the mineralized portion and organic portion of bone. Titanium had less transport but still showed levels in the experimental animals in plasma, kidney, liver, spleen, and both phases of bone above those in the control animals. Neither element was found above control levels in lung or red blood cells. The levels of titanium and vanadium in control bone were high, possibly indicating bone as a site for storage and accumulation of these elements when encountered in the activities of daily living.

Animals↗

X-ray structure determination of a vanadium-dependent haloperoxidase from Ascophyllum nodosum at 2.0 A resolution.

The homo-dimeric structure of a vanadium-dependent haloperoxidase (V-BPO) from the brown alga Ascophyllum nodosum (EC 1.1.11.X) has been solved by single isomorphous replacement anomalous scattering (SIRAS) X-ray crystallography at 2.0 A resolution (PDB accession code 1QI9), using two heavy-atom datasets of a tungstate derivative measured at two different wavelengths. The protein sequence (SwissProt entry code P81701) of V-BPO was established by combining results from protein and DNA sequencing, and electron density interpretation. The enzyme has nearly an all-helical structure, with two four-helix bundles and only three small beta-sheets. The holoenzyme contains trigonal-bipyramidal coordinated vanadium atoms at its two active centres. Structural similarity to the only other structurally characterized vanadium-dependent chloroperoxidase (V-CPO) from Curvularia inaequalis exists in the vicinity of the active site and to a lesser extent in the central four-helix bundle. Despite the low sequence and structural similarity between V-BPO and V-CPO, the vanadium binding centres are highly conserved on the N-terminal side of an alpha-helix and include the proposed catalytic histidine residue (His418(V-BPO)/His404(V-CPO)). The V-BPO structure contains, in addition, a second histidine near the active site (His411(V-BPO)), which can alter the redox potential of the catalytically active VO2-O2 species by protonation/deprotonation reactions. Specific binding sites for the organic substrates, like indoles and monochlordimedone, or for halide ions are not visible in the V-BPO structure. A reaction mechanism for the enzymatic oxidation of halides is discussed, based on the present structural, spectroscopic and biochemical knowledge of vanadium-dependent haloperoxidases, explaining the observed enzymatic differences between both enzymes.

Amino Acid Sequence↗

Separation and determination of vanadium in fertiliser by capillary electrophoresis with a light-emitting diode detector.

A method has been developed for determination of vanadium, as an anionic ternary complex of vanadium(V) with 4-(2-pyridylazo) resorcinol (PAR) and hydrogen peroxide, after separation by capillary electrophoresis (CE). The optimum conditions for the formation of the ternary complex were acetate buffer (3 mmol L(-1)) at pH 6 containing 0.15 mmol L(-1) PAR and 7.1 mmol L(-1) H(2)O(2). The CE separation was conducted using 15 mmol L(-1) acetate buffer at pH 6 as the background electrolyte; the separation potential was -30 kV and the injection time 100 s. The vanadium complex was detected photometrically at 568 nm, by use of a light-emitting diode (LED); the detection limit was 19 ppb. The method was applied to the analysis of vanadium in fertilisers. Clean-up of the digested fertiliser sample, with Sep-Pak C(18) coated with tetrabutylammonium hydroxide, before analysis was used to remove matrix ions which otherwise caused electrophoretic de-stacking. Vanadium levels found in the fertiliser samples by use of the CE method were found to be comparable with results obtained by HPLC and ICP-MS.

Journal Article↗

Carcinogen-induced early molecular events and its implication in the initiation of chemical hepatocarcinogenesis in rats: chemopreventive role of vanadium on this process.

Carcinogen-induced formation of DNA adducts and other types of DNA lesions are the critical molecular events in the initiation of chemical carcinogenesis and modulation of such events by chemopreventive agents could be an important step in limiting neoplastic transformation in vivo. Vanadium, a dietary micronutrient has been found to be effective in several types of cancers both in vivo and in vitro and also possesses profound anticarcinogenicity against rat models of mammary, colon and hepatocarcinogenesis. Presently, we report the chemopreventive potential of vanadium on diethylnitrosamine (DEN)-induced early DNA damages in rat liver. Hepatocarcinogenesis was induced in male Sprague-Dawley rats with a single, necrogenic, intraperitoneal (i.p.) injection of DEN (200 mg/kg body weight) at week 4. There was a significant induction of tissue-specific ethylguanines, steady elevation of modified DNA bases 8-hydroxy-2'-deoxyguanosines (8-OHdGs) (P<0.0001; 89.93%) along with substantial increment of the extent of single-strand breaks (SSBs) (P<0.0001) following DEN exposure. Supplementation of 0.5 ppm of vanadium throughout the experiment abated the formations of O(6)-ethylguanines and 7-ethylguanines (P<0.0001; 48.71% and 67.54% respectively), 8-OHdGs (P<0.0001; 81.37%), length:width (L:W) of DNA mass (P<0.01; 62.12%) and the mean frequency of tailed DNA (P<0.001; 53.58%), and hepatic nodulogenesis in preneoplastic rat liver. The study indicates that 0.5 ppm vanadium is potentially and optimally effective, as derived from dose-response studies, in limiting early molecular events and preneoplastic lesions, thereby modulating the initiation stage of hepatocarcinogenesis. Vanadium is chemopreventive against DEN-induced genotoxicity and resulting hepatocellular transformation in rats.

Alkylating Agents↗

Interactions of vanadium(V)-citrate complexes with the sarcoplasmic reticulum calcium pump.

Among the biotargets interacting with vanadium is the calcium pump from the sarcoplasmic reticulum (SR). To this end, initial research efforts were launched with two vanadium(V)-citrate complexes, namely (NH(4))(6)[V(2)O(4)(C(6)H(4)O(7))(2)].6H(2)O and (NH(4))(6)[V(2)O(2)(O(2))(2)(C(6)H(4)O(7))(2)].4H(2)O, potentially capable of interacting with the SR calcium pump by combining kinetic studies with (51)V NMR spectroscopy. Upon dissolution in the reaction medium (concentration range: 4-0.5mM), both vanadium(V):citrate (VC) and peroxovanadium(V):citrate (PVC) complexes are partially converted into vanadate oligomers. A 1mM solution of the PVC complex, containing 184microM of the PVC complex, 94microM oxoperoxovanadium(V) (PV) species, 222microM monomeric (V1), 43microM dimeric (V2) and 53microM tetrameric (V4) species, inhibits Ca(2+) accumulation by 75 %, whereas a solution of the VC complex of the same vanadium concentration, containing 98microM of the VC complex, 263microM monomeric (V1), 64microM dimeric (V2) and 92microM tetrameric (V4) species inhibits the calcium pump activity by 33 %. In contrast, a 1 mM metavanadate solution, containing 460microM monomeric (V1), 90.2microM dimeric (V2) and 80microM tetrameric (V4) species, has no effect on Ca(2+) accumulation. The NMR signals from the VC complex (-548.0ppm), PVC complex (-551.5ppm) and PV (-611.1ppm) are broadened upon SR vesicle addition (2.5mg/ml total protein). The relative order for the half width line broadening of the NMR signals, which reflect the interaction with the protein, was found to be V4>PVC>VC>PV>V2=V1=1, with no effect observed for the V1 and V2 signals. Putting it all together the effects of two vanadium(V)-citrate complexes on the modulation of calcium accumulation and ATP hydrolysis by the SR calcium pump reflected the observed variable reactivity into the nature of key species forming upon dissolution of the title complexes in the reaction media.

Animals↗