Metabolic effects, vanadium

Extrapolating from well-characterized enzymatic inhibition in test tubes, numerous mechanistic ideas concerning the in vivo effects of vanadium compounds have been advanced. The effects of vanadium compounds as transition-state analogs of certain enzymes with a phosphoprotein intermediate in their reaction scheme is proposed to account for the action of vanadium [11] in many biological systems. Unfortunately, it is often difficult to determine if the inhibition observed in the test tube occurs in vivo. For example, although vanadate is a potent inhibitor of plasma membrane ion pumps (such as the sodium potassium ATPase) in the test tube, it is difficult to determine if these pumps are actually inhibited in animals exposed to vanadium compounds. Currently, the role of vanadium compounds as protein phosphatase (PTP) inhibitors is believed to be related to the metabolic effects of this... 

Vanadate(V) has been shown to block the activation of a progesterone receptor complex from avian oviduct104. Whether this effect involves phosphate metabolism is not known. A possible link between hormonal effects and the metabolism of vanadium in the reproductive physiology of rats has been investigated165"167. ... 

Insulin-like actions of vanadium potential as a therapeutic agent (2003), ] in which the molecular mechanisms underlying the metabolic effects of vanadium in vivo are highlighted. 

Vanadium has been shown to have many metabolic effects. One study showed, that rats fed vanadium pentoxide had a lowered cystine content in their hair, and workers exposed to vanadium a lowered cystine content in their fingernails [7]. This indicates that vanadium causes a decrease in the synthesis of cystine and cysteine. More research on the toxicity of vanadium and its salts is needed. 

Birnboim, H.C. (1988). A superoxide anion induced DNA strand-break metabolic pathway in human leukocytes effect of vanadium. Biochem. Cell. Biol. 66, 374-381. 

Chromium has proved effective in counteracting the deleterious effects of cadmium in rats and of vanadium in chickens. High mortality rates and testicular atrophy occurred in rats subjected to an intraperitoneal injection of cadmium salts however, pretreatment with chromium ameliorated these effects (Stacey et al. 1983). The Cr-Cd relationship is not simple. In some cases, cadmium is known to suppress adverse effects induced in Chinese hamster (Cricetus spp.) ovary cells by Cr (Shimada et al. 1998). In southwestern Sweden, there was an 80% decline in chromium burdens in liver of the moose (Alces alces) between 1982 and 1992 from 0.21 to 0.07 mg Cr/kg FW (Frank et al. 1994). During this same period in this locale, moose experienced an unknown disease caused by a secondary copper deficiency due to elevated molybdenum levels as well as chromium deficiency and trace element imbalance (Frank et al. 1994). In chickens (Gallus sp.), 10 mg/kg of dietary chromium counteracted adverse effects on albumin metabolism and egg shell quality induced by 10 mg/kg of vanadium salts (Jensen and Maurice 1980). Additional research on the beneficial aspects of chromium in living resources appears warranted, especially where the organism is subjected to complex mixtures containing chromium and other potentially toxic heavy metals. 

High levels of dietary tin increased zinc loss from rats (Greger 1989). Zinc prevented toxic effects of vanadium (10 mg/kg BW) on bone metabolism of weanling rats (Yamaguchi et al. 1989). 

Yamaguchi, M., H. Oishi, and Y. Suketa. 1989. Effect of vanadium on bone metabolism in weanling rats zinc prevents the toxic effect of vanadium. Res. Exper. Medic. 189 47-53. 

The role of these interesting plasma membrane-dependent, vanadate-stimulated NAD(P)H oxidation reactions in cellular metabolism remains to be elucidated, although multiple interactions with cellular metabolism and components are possible including interactions with xanthine oxidase and lipid peroxidation [24], Decavanadate has been shown to enhance cytochrome c reduction [31], and cytochrome c release from mitochondria is associated with initiation of apoptosis. Perhaps the reduced cytochrome c is more readily released from the mitochondria. With increasing emphasis on the redox properties of vanadium being important in its pharmacological effects, it is quite possible that these reactions, either protein dependent or not, may play a role in therapeutic actions of vanadium. 

Vanadium has effects similar to and different from that of insulin [100,101,124], The antidiabetic influence of the metal can be considered insulin-enhancing, rather than insulin-mimetic, because vanadium compounds cannot totally substitute for insulin in any model of diabetes that strictly requires insulin, such as the BB rat [125], a model of type 1 diabetes. In addition, vanadium can exert its antidiabetic effects via a mechanism or combination of mechanisms distinct from that of insulin. The metabolic actions of vanadium on metabolism do not include all of the actions of insulin, yet normal animals produce less serum insulin when given vanadium. The terms insulin-mimetic or insulin-like frequently appear in the literature for actions of vanadium that cannot be classified as similar to or different from that of insulin in the experimental system utilized. 

Simulation of glucose transport and glucose transporter translocation from intracellular stores to the plasma membrane in muscle cells by vanadate and peroxovan-adate involve a mechanism independent of PI-3K and protein kinase C systems utilized for stimulation of these processes by insulin. The transport of GLUT4 to the plasma membrane in muscle cells growing in culture after stimulation by vanadate, peroxovanadate, or insulin all require an intact actin network [138], Sometimes, the insulin-like action of vanadium is accompanied by overall stimulation of actual metabolic pathways. One example of this is the stimulation of the pentose phosphate pathway observed when vanadate promotes the incorporation of glucose into lipids, an antilipogenic effect [139],... 

The influences of vanadium compounds on cardiovascular function, a major complication of diabetes, has been reviewed [144], One of the first papers on the antidiabetic effects of oral administration of vanadium compounds (vanadyl sulfate) to rats with STZ-induced diabetes showed improvement of diabetes-impaired cardiac function [122], Recent work has focused on the correction of metabolic defects of diabetes by vanadium and learning more about the immediate mechanism of the antidiabetic effect. The assumption is made that amelioration of the basic metabolic problems of diabetes by vanadium or any other drug will alleviate the long-term complication arising from disease. Diet supplementation with minerals, such as chromium, appears to complement traditional treatments of diabetes to slow the development of complications. Mineral supplementation is believed to be most effective when dietary supplementation is used to correct a deficiency of a mineral [145],... 

Possible relationship between vanadium metabolism and hormonal effects in reproduction 164-167... 

By using radioisotopes, the influx of vanadate into the blood cells of A. nigra has been studied85. The influx of phosphate, sulfate and dichromate, and the inhibitory effect of these oxoanions on vanadate influx have also been determined. The rate of vanadate influx was measured in the presence of metabolic inhibitors and inhibitors of anion transport. In this study, EPR spectroscopy was used to follow changes in the concentration of reduced vanadium within tunicate blood cells exposed to vanadate. 

For some trace elements, continued suboptimal dietary intake— in the presence of physiological, nutritional, or other metabolic stress— may eventually have a detrimental effect. Then additional dietary supplementation may have a health restorative effect. Such effects are most clearly demonstrated in experimental animals. Examples include the effects of boron in the presence of vitamin D depletion, or the need for increased vanadium when there is either an experimentally induced deficient or excess supply of dietary iodine. ... 

Kacew S, Parulekar MR, Merali Z. 1982. Effects of parenteral vanadium administration on pulmonary metabolism of rats. Toxicol Lett 11 119-124. 

Sabbioni E, Clerici L, Brazzelli A. 1983. Different effects of vanadium ions on some DNA-metabolizing enzymes. J Toxicol Environ Health 12 737-748. 

---