Vanadium Abstracts 3

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Vanadium inhibition of cholesterol synthesis in man.
            (1960) Download
Salts of vanadium have the unique property of inhibiting the utilization of mevalonic acid for cholesterol synthesis according to Azarnoff and Curran (J.Am. Chem. Soc. 79,2968 (1957)) Curran, Azarnoff and R. E. Bolinger (J. Clin. Invest. 38, 1251 (1959)) have recently examined the effects of vanadium on sterol balance in normal men on a rigidly controlled diet.

Site of vanadium inhibition of cholesterol biosynthesis
            (Azarnoff, 1957) Download
Vanadium compounds have been shown to inhibit the incorporation of radioacetate into cholesterol by rat and rabbit liver in vitro and in vivo. This communication demonstrates that the inhibition by vanadium occurs between the six and five carbon intermediates. These data are interpreted as demonstrating that vanadium inhibits cholesterol biosynthesis between HMG (Beta-hydroxy- beta-methyl glutarate) and BMC (Beta-methyl crotonate). Vanadium also inhibits the conversion of mevalonic acid to cholesterol.

Four-week supplementation with a natural dietary compound produces favorable changes in body composition.
            (Hoeger et al., 1998)  Download
The purpose of this study was to determine whether a natural dietary supplement produced favorable changes in body composition during a 4-week diet- and-exercise program. The active compound contains a patented combination of chromium picolinate, inulin, capsicum, L-phenylalanine, and other lipotropic nutrients. A double-blind, weight-loss intervention design was used. Participants were randomly assigned to either a diet/exercise/supplement group (n = 56) or a diet/exercise/placebo group (n = 67). Caloric intake was reduced to 1500 kcal/d and participants walked for 45 minutes, 5 days a week, to attain between 60% and 80% of predicted maximal heart rate. Analysis of covariance (ANCOVA) showed significant differences (P < .05) between groups in percent body fat, fat mass, and fat-free mass; no significant differences were found (P > .05) in body weight, body mass index, or energy intake. Independent t tests showed no significant differences (P > .05) in diet composition between groups. Results indicate that the addition of a natural dietary supplement during a 4-week diet-and-exercise weight-loss program accelerates the rate of body fat loss and helps maintain fat-free mass (lean tissue), thereby producing favorable changes in body composition.

Comparative erythropoietic effects of three vanadium compounds.
            (Hogan, 2000) Download
The biotoxic effects of vanadium are variable depending upon a number of factors including the oxidation state of the test compound. This study reports the effects of three vanadium compounds on peripheral erythrocytes. On day 0 female ICR mice received a single injection of vanadium chloride (V-III), vanadyl sulfate (V-IV), or sodium orthovandate (V-V). At scheduled intervals post-injection, the number of circulating erythrocytes [red blood cells per millimeter cubed (RBC/mm3)], reticulocyte percentages, and radioiron uptake percentages were determined and compared to mice receiving saline only. Data show that all three test substances promoted a significant lowering of RBC/mm3 beginning on day 1 for V-IV and V-V and on day 2 for V-III through day 4. The reticulocyte percentages increase followed the same time course as that of the peripheral RBC decrease. Peak reticulocytosis was noted on days 2 and 4 for all three vanadium-treated groups; for V-IV and V-V the increase continued to day 6. Radioiron data showed an erythropoietic stimulation by a significant increase in uptake percentages on days 4-6 after vanadium injections compared to saline-treated controls.

Vanadium. Its role for humans.
            (Rehder, 2013) Download
Vanadium is the 21st most abundant element in the Earth's crust and the 2nd-to-most abundant transition metal in sea water. The element is ubiquitous also in freshwater and nutrients. The average body load of a human individual amounts to 1 mg. The omnipresence of vanadium hampers checks directed towards its essentiality. However, since vanadate can be considered a close blueprint of phosphate with respect to its built-up, vanadate likely takes over a regulatory function in metabolic processes depending on phosphate. At common concentrations, vanadium is non-toxic. The main source for potentially toxic effects caused by vanadium is exposure to high loads of vanadium oxides in the breathing air of vanadium processing industrial enterprises. Vanadium can enter the body via the lungs or, more commonly, the stomach. Most of the dietary vanadium is excreted. The amount of vanadium resorbed in the gastrointestinal tract is a function of its oxidation state (V(V) or V(IV)) and the coordination environment. Vanadium compounds that enter the blood stream are subjected to speciation. The predominant vanadium species in blood are vanadate and vanadyl bound to transferrin. From the blood stream, vanadium becomes distributed to the body tissues and bones. Bones act as storage pool for vanadate. The aqueous chemistry of vanadium(V) at concentration <10 μM is dominated by vanadate. At higher concentrations, oligovanadates come in, decavanadate in particular, which is thermodynamically stable in the pH range 2.3-6.3, and can further be stabilized at higher pH by interaction with proteins.The similarity between vanadate and phosphate accounts for the interplay between vanadate and phosphate-dependent enzymes: phosphatases can be inhibited, kinases activated. As far as medicinal applications of vanadium compounds are concerned, vanadium's mode of action appears to be related to the phosphate-vanadate antagonism, to the direct interaction of vanadium compounds or fragments thereof with DNA, and to vanadium's contribution to a balanced tissue level of reactive oxygen species. So far vanadium compounds have not yet found approval for medicinal applications. The antidiabetic (insulin-enhancing) effect, however, of a singular vanadium complex, bis(ethylmaltolato)oxidovanadium(IV) (BEOV), has revealed encouraging results in phase IIa clinical tests. In addition, in vitro studies with cell cultures and parasites, as well as in vivo studies with animals, have revealed a broad potential spectrum for the application of vanadium coordination compounds in the treatment of cardiac and neuronal disorders, malignant tumors, viral and bacterial infections (such as influenza, HIV, and tuberculosis), and tropical diseases caused by parasites, e.g., Chagas' disease, leishmaniasis, and amoebiasis.

Studies on the effect of vanadate on endocytosis and shape changes in human red blood cells and ghosts.
            (Schrier et al., 1986) Download
When amphipathic cationic drugs are added to intact human RBCs, the RBCs first undergo a stomatocytic shape change and then, if relatively large amounts of drug are added and if the metabolic state of the RBC is appropriate, endocytic vacuoles form. Vanadate has a structural similarity to the transition state of phosphate, which presumably accounts for its ability to inhibit phosphohydrolases, although other actions of vanadate have been described. Vanadate inhibited three forms of drug-induced endocytosis in intact RBCs despite the fact that the three drugs chosen (primaquine, chlorpromazine, and vinblastine) are known to have differing requirements for RBC ATP. Vanadate also inhibited the stomatocytic shape change produced by primaquine, chlorpromazine, and vinblastine, but not the stomatocytosis produced by low pH. Vanadate had no effect on RBC echinocytosis produced by lysophosphatidylcholine. In studying endocytosis in hypotonic, leaky, "white" ghosts, we discovered that vanadate inhibited only the endocytosis produced by Mg-ATP and not the endocytosis produced by manipulations that directly attack the cytoskeletal proteins. These findings suggest that ATP hydrolysis has a role in some forms of amphipathic cation-induced stomatocytosis and endocytosis in intact RBCs. In addition, studies in ghosts support the idea that Mg-ATP does indeed produce "energized" endocytosis dependent on utilization or hydrolysis of ATP.


 

Antihypertensive effects of metal binding agents.
            (Schroeder and Perry, 1955) Download
Non-neurogenically acting antihypertensive agents (thiocyanate, nitroprusside, azide, hydrazinophthalazines, mercaptans) have in common an affinity for transition and nearby metals. Therefore, 5 mg. each of a series of nine disodium ethylenediamine tetraacetates (EDTA) of increasingly tightly bound divalent metals was assayed for vasoactivity in groups of normotensive and renal hypertensive rats, blood presure being recorded on a manometer.

A practical method for the reduction of plasma cholesterol in man.
            (Schroeder, 1956) Download
A practical method has been devised to lower plasma cholesterol in ambula- tory patients, based on a diet fairly low in saturated fatty acids but providing an adequate intake of linolenic acid, a metal chelator, and pyridoxine. Plasma levels fell variably but considerably in most of 20 patients. The rationale of such a regimen in metabolic terms has been discussed.

Abnormal Trace Metals In Man--Vanadium.
            (Schroeder et al., 1963) Download
Vanadium was discovered in 1801 by Del Rio who called it erythronium. Later he decided that it was a form of chromium. Not until 1831 was it finally identified by Sefstrom who namea it after Vanaciis, the race of Freia, the Norse goddess of beauty. Such beauty as it may have is chemical, lying in its excellent catalytic properties and physical, in the color of its compounds, but not particularly in the green tongues it causes in exposed workers

Interrelations between Essential Metal Ions and Human Diseases BOOK
            (Sigel et al., 2013) Download
Trace elements (TEs) are required by both humans and bacterial pathogens. Although metal ion homeostasis is tightly controlled in humans, growing evidence suggests that pathogens utilize a variety of means designed to circumvent the sequestration of TEs. Colonizing pathogenic microorganisms employ a variety of strategies to sense, acquire, store, and export metal ions in the vertebrate host which include the biosynthesis and utilization of siderophores, and the expression of high-affinity metal-ion transporters.


 

The site of vanadyl inhibition of cholesterol biosynthesis in liver homogenates.
            (Wright et al., 1960) Download
Cholesterol (CHL) biosynthesid both in titro (1,2) snd in viva (3-6) is reported to be inhibited by vanadium salts. This inhibition appears to involve reactions between mevalonic acid (MVA) and CHL but the exact locus has not been more specificlly defined. Data reported in this connrmnicatlon demonstrate that with rat liver homogenates vanadium is an inhibitor of oxidative phosphorylation and that vanadyl inhibition of CHL biosynthesis is, in all probability, a reflection of the inability of a system to maintain a functional level of ATP.

Haematological effects of vanadium on living organisms.
            (Zaporowska and Wasilewski, 1992) Download
Although vanadium has been of great interest for many researchers over a number of years, its biochemical and physiological role is not yet fully clear. There are many papers describing the haematological consequences of its excess in living organisms and most of their data are quoted in this mini-review. The authors of these papers used various laboratory animals, different vanadium compounds, frequently different routes of administration and duration of intoxication. Hence a checklist and comparison of the results are rather difficult. Vanadium reduces the deformability of erythrocytes, and such cells are rather frequently retained in the reticuloendothelial system of the spleen and eliminated faster from the blood stream (Kogawa et al., 1976). Vanadium produces peroxidative changes in the erythrocyte membrane, this leading to haemolysis. Therefore, the depressed erythrocyte count in animals intoxicated with vanadium may be the consequence of both the haemolytic action of vanadium and the shortened time of survival of erythrocytes. Changes of the haem precursor level in blood serum and urine observed in humans exposed occupationally to vanadium suggest an influence of this element on haem synthesis. This problem requires, however, further studies and observations. Changes occurring under the influence of vanadium on the leukocyte system of animals suggest the influence of this element on the resistance of the organism, but the mechanism of the action of vanadium still requires elucidation.(ABSTRACT TRUNCATED AT 250 WORDS)

 


References

Azarnoff, DL (1957), ‘Site of vanadium inhibition of cholesterol biosynthesis’, J Am Chem Soc, 79 (11), 2968-69. PubMed:
Hoeger, WW, et al. (1998), ‘Four-week supplementation with a natural dietary compound produces favorable changes in body composition.’, Adv Ther, 15 (5), 305-14. PubMed: 10345151
Hogan, GR (2000), ‘Comparative erythropoietic effects of three vanadium compounds.’, Sci Total Environ, 256 (2-3), 185-89. PubMed: 10902845
Rehder, D (2013), ‘Vanadium. Its role for humans.’, Met Ions Life Sci, 13 139-69. PubMed: 24470091
Schrier, SL, I Junga, and L Ma (1986), ‘Studies on the effect of vanadate on endocytosis and shape changes in human red blood cells and ghosts.’, Blood, 68 (5), 1008-14. PubMed: 2945602
Schroeder, HA and HM Perry (1955), ‘Antihypertensive effects of metal binding agents.’, J Lab Clin Med, 46 (3), 416-22. PubMed: 13252320
Schroeder, HA (1956), ‘A practical method for the reduction of plasma cholesterol in man.’, J Chronic Dis, 4 (5), 461-68. PubMed: 13367144
Schroeder, HA, JJ BALASSA, and IH TIPTON (1963), ‘Abnormal Trace Metals In Man--Vanadium.’, J Chronic Dis, 16 1047-71. PubMed: 14068919
(2013), Interrelations between Essential Metal Ions and Human Diseases, eds. Sigel, A, H Sigel, and R Sigel, (Metal Ions in Life Sciences, 13; New York: Springer).
(1960), ‘Vanadium inhibition of cholesterol synthesis in man.’, Nutr Rev, 18 39-42. PubMed: 13857967
Wright, LD, LF Li, and R Trager (1960), ‘The site of vanadyl inhibition of cholesterol biosynthesis in liver homogenates.’, Biochem Biophys Res Commun, 3 264-67. PubMed: 13786802
Zaporowska, H and W Wasilewski (1992), ‘Haematological effects of vanadium on living organisms.’, Comp Biochem Physiol C, 102 (2), 223-31. PubMed: 1358535