Effects of vanadium (V) and magnesium (Mg) on rat bone tissue: mineral status and micromorphology. Consequences of V-Mg interactions.

The extent to which the 12 week separate and combined administration of vanadium (as sodium metavanadate--SMV, 0.125 mg V per ml) and magnesium (as magnesium sulphate--MS, 0.06 mg Mg per ml) affects bone mineral status and micromorphology as well as the alkaline phosphatase (ALP) activity in femoral diaphysis (FD) was examined in male rats. The bone chemical composition of SMV-exposed rats was also investigated. SMV alone or in combination with MS (as SMV-MS) reduced the levels of MgFD (by 21% and 20%) and PFD (by 12% and 9%), lowered the CaFD content (by 7% and 10%), and caused a rise of the FeFD concentration (by 22.5% and 17%), compared with the control; SMV alone also reduced and enhanced the KFD and ZnFD concentrations (by 19% and 15%, respectively) but remained without significant effect on the femoral bone surface roughness (FBSR), whereas MS alone lowered the VFD, PFD, and CuFD levels (by 42%, 10%, and 20.6%), reduced FBSR, and created the regular femoral bone surface shape. The SMV-MS combination also induced a decline and rise in the levels of CuFD (by 30%) and NaFD (by 15%), respectively, compared with the control and the MS-supplemented rats; elevated ALPFD activity (by 24%, 35%, and 40%), compared with the control, SMV-exposed, and MS-supplemented animals; and increased FBSR. Relationships between the root mean square roughness (Sq) and skewness (Ssk): Sq [MS < SMV < Control < SMV-MS] ⇔ Ssk [SMV-MS > Control > SMV > MS], ALPFD and Sq: ALPFD⇔ Sq [SMV-MS > Control > SMV > MS], and between other variables were demonstrated. A partial limitation of the drop in the PFD and KFD levels and normalization of the ZnFD concentration were a consequence of the V-Mg antagonistic interaction whereas a consequence of the V-Mg synergistic interaction was the increase in the NaFD level, ALPFD activity, and FBSR. Ca10(PO4)5(SiO4)(OH) was part of the inorganic component of the bone of the SMV-exposed rats.

Essentiality and toxicity of vanadium supplements in health and pathology.

The biological properties of vanadium complexes have become an object of interest due to their therapeutic potential in several diseases. However, the mechanisms of action of vanadium salts are still poorly understood. Vanadium complexes are cofactors for several enzymes and also exhibit insulin-mimetic properties. Thus, they are involved in the regulation of glucose metabolism, including in patients with diabetes. In addition, vanadium salts may also normalize blood pressure and play a key role in the metabolism of the thyroid and of iron as well as in the regulation of total cholesterol, cholesterol HDL and triglyceride (TG) levels in blood. Moreover, in cases of hypoxia, vanadium compounds may improve cardiomyocytes function. They may also exhibit both carcinogenic and anti-cancer properties. These include dose- and exposure-time-dependent induction and inhibition of the proliferation and survival of cancer cells. On the other hand, the balance between vanadium's therapeutic properties and its side effects has not yet been determined. Therefore, any studies on the potential use of vanadium compounds as supplements to support the treatment of a number of diseases must be strictly monitored for adverse effects.

Uptake and speciation of vanadium in the benthic invertebrate Hyalella azteca.

Vanadium has the potential to leach into the environment from petroleum coke, an oil sands byproduct. To determine uptake of vanadium species in the biota, we exposed the benthic invertebrate Hyalella azteca with increasing concentrations of two different vanadium species, V(IV) and V(V), for seven days. The concentrations of vanadium in the H. azteca tissue increased with the concentration of vanadium in the exposure water. Speciation analysis revealed that V(IV) in the exposure water was oxidized to V(V) between renewal periods, and therefore the animals were mostly exposed to V(V). Speciation analysis of the H. azteca tissue showed the presence of V(V), V(IV), and an unidentified vanadium species. These results indicate the uptake and metabolism of vanadium by H. azteca. Because H. azteca are widely distributed in freshwater systems and are an important food supply for many fish, determining the uptake and metabolism of vanadium allows for a better understanding of the potential environmental effects on invertebrates.

The use of feathers in monitoring bioaccumulation of metals and metalloids in the South African endangered African grass-owl (Tyto capensis).

Few studies have quantified metals in South African species and no published data on residues specifically in South African owl feathers exist. Tyto capensis is listed as vulnerable within South Africa, making it preferable to use a non-invasive technique to determine metal bioaccumulation for this species. Comparisons are made with the cosmopolitan T. alba to determine whether this species could be used as a surrogate. Concentrations of various metals were thus determined in feathers of the two species and compared with liver and muscle samples. Samples were taken from 119 owls collected as road kill along a national road. A comparison of concentrations in feathers revealed similarly higher concentrations of aluminium, antimony, lead, nickel, and strontium, whereas concentrations of chromium, copper, iron, manganese, selenium, titanium and zinc were similarly higher in internal tissues for both species. Metal concentrations of owls were comparable to those reported in literature and below toxic levels, suggesting that these metals were not likely to impact the owls. Further regressions between feathers and corresponding livers were examined to determine if feathers were indicative of internal metal burdens. Significant positive relationships were found for aluminium, copper, lead, nickel and vanadium in T. alba and nickel, manganese and vanadium in T. capensis. Preliminary results support the feasibility of using feathers as non-destructive indicators of environmental contamination in T. capensis although caution needs to be taken when interpreting the results.

Bioavailability, tissue distribution and hypoglycaemic effect of vanadium in magnesium-deficient rats.

Vanadium is an element whose role as a micronutrient and hypoglycaemic drug has yet to be fully clarified. The present study was undertaken to investigate the bioavailability and tissue distribution of vanadium and its interactions with magnesium in healthy and in magnesium-deficient rats, in order to determine its role as a micronutrient and antidiabetic agent. Four groups were used: control (456.4 mg magnesium and 0.06 mg vanadium/kg food); control treated with 1mg vanadium/day; magnesium-deficient (164.4 mg magnesium/kg food and 0.06 mg vanadium/kg food); and magnesium-deficient treated with 1 mg vanadium/day. The vanadium was supplied in the drinking water as bis(maltolato)oxovanadium (IV). The experiment had a duration of five weeks. We measured vanadium and magnesium in excreta, serum, skeletal muscle, kidney, liver, adipose tissue and femur. Fasting glucose, insulin and total antioxidant status (TAS) in serum were studied. The vanadium treatment applied to the control rats reduced the absorption, retention, serum level and femur content of magnesium. Magnesium deficiency increased the retention and serum level of vanadium, the content of vanadium in the kidney, liver and femur (organs where magnesium had been depleted), serum glycaemia and insulin, and reduced TAS. V treatment given to magnesium-deficient rats corrected magnesium content in muscle, kidney and liver and levels of serum glucose, insulin and TAS. In conclusion, our results show interactions between magnesium and vanadium in the digestive and renal systems. Treatment with vanadium to magnesium-deficient rats corrected many of the alterations that had been generated by the magnesium deficiency.

Toxicity and hazard of vanadium to mallard ducks (Anas platyrhynchos) and Canada geese (Branta canadensis).

A recent Canada goose (Branta canadensis) die-off at a petroleum refinery fly ash pond in Delaware was attributed to vanadium (V) toxicity. Because of the paucity of V toxicity data for wild birds, a series of studies was undertaken using the forms of V believed to have resulted in this incident. In 7-d single oral dose trials with mallard drakes (Anas platyrhynchos), the estimated median lethal dose (LD50) for vanadium pentoxide was 113 mg/kg body weight, while the LD50 for sodium metavanadate was 75.5 mg/kg. Sodium metavanadate was found to be even more potent (LD50 = 37.2 mg/kg) in male Canada geese. The most distinctive histopathological lesion of both forms of V was lympho-granulocytic enteritis with hemorrhage into the intestinal lumen. Vanadium accumulation in liver and kidney was proportional to the administered dose, and predictive analyses based on these data suggest that V concentrations of 10 microg/g dry weight (dw) in liver and 25 microg/g dw in kidney are associated with mortality (>90% confidence that exposure is >LD50) in mallards acutely exposed to sodium metavanadate. Chronic exposure to increasing dietary concentrations of sodium metavanadate (38.5 to 2651 ppm) over 67 d resulted in V accumulation in liver and kidney (25.2 and 13.6 microg/g dw, respectively), mild intestinal hemorrhage, blood chemistry changes, and evidence of hepatic oxidative stress in mallards, although some of these responses may have been confounded by food avoidance and weight loss. Dietary exposure of mallards to 250 ppm sodium metavanadate for 4 wk resulted in modest accumulation of V in liver and kidney (<5 microg/g dw) and mild intestinal hemorrhage. Based on these data and other observations, it is unlikely that chronic low-level dietary exposure to V poses a direct lethal hazard to wildlife. However, point sources, such as the V-laden fly ash pond encountered by geese at the petroleum refinery in Delaware, may pose a significant hazard to water birds.

Liver and kidney concentrations of vanadium in oiled seabirds after the Erika wreck.

Vanadium was measured by atomic absorption spectrophotometry in the liver and kidney of several oiled seabirds that were stranded on the French Atlantic coasts after the Erika wreck and died in wildlife care Centers. Estimated averages were 30 to 77 ng g(-1) wet weight (ww) in the liver and 52 to 72 ng g(-1) wet weight in the kidney. These concentrations were not higher in oiled birds than in dead birds found later, without visible traces of petroleum on beaches not affected by the Erika pollution. Vanadium hepatic and renal concentrations do not seem to be appropriate biomarkers for recent exposure to fuel in seabirds.

Influence of chelation and oxidation state on vanadium bioavailability, and their effects on tissue concentrations of zinc, copper, and iron.

Today, vanadium compounds are frequently included in nutritional supplements and are also being developed for therapeutic use in diabetes mellitus. Previously, tissue uptake of vanadium from bis(maltolato)oxovanadium(IV) (BMOV) was shown to be increased compared to its uptake from vanadyl sulfate (VS). Our primary objective was to test the hypothesis that complexation increases vanadium uptake and that this effect is independent of oxidation state. A secondary objective was to compare the effects of vanadium complexation and oxidation state on tissue iron, copper, and zinc. Wistar rats were fed either ammonium metavanadate (AMV), VS, or BMOV (1.2 mM each in the drinking water). Tissue uptake of V following 12 wk of BMOV or AMV was higher than that from VS (p < 0.05). BMOV led to decreased tissue Zn and increased bone Fe content. The same three compounds were compared in a cellular model of absorption (Caco-2 cells). Vanadium uptake from VS was higher than that from BMOV or AMV at 10 min, but from BMOV (250 microM only, 60 min), uptake was far greater than from AMV or VS. These results show that neither complexation nor oxidation state alone are adequate predictors of relative absorption, tissue accumulation, or trace element interactions.

Bioaccumulation of vanadium in the epiphytic lichen Parmelia caperata from Liguria (north-west Italy).

The concentration of vanadium was measured in 35 samples of the epiphytic lichen Parmelia caperata collected along the coast of the Ligurian Sea (Italy), in order to detect the possible bioaccumulation of vanadium due to a huge crude oil burning occurred in that area in 1991. The cartographic elaboration of data shows a pattern of distribution of vanadium concentrations according to different degrees of deviation from background condition, showing that 8 years later memory of the accident is still detectable in foliose lichen thalli.

Vanadium.

Vanadium is a steel-grey, corrosion-resistant metal, which exists in oxidation states ranging from -1 to +5. Metallic vanadium does not occur in nature, and the most common valence states are +3, +4, and +5. The pentavalent form (VO3-) predominates in extracellular body fluids whereas the quadrivalent form (VO+2) is the most common intracellular form. Because of its hardness and its ability to form alloys, vanadium (i.e., ferrovanadium) is a common component of hard steel alloys used in machines and tools. Although most foods contain low concentrations of vanadium (< 1 ng/g), food is the major source of exposure to vanadium for the general population. High air concentrations of vanadium occur in the occupation setting during boiler-cleaning operations as a result of the presence of vanadium oxides in the dust. The lungs absorb soluble vanadium compounds (V2O5) well, but the absorption of vanadium salts from the gastrointestinal tract is poor. The excretion of vanadium by the kidneys is rapid with a biological half-life of 20-40 hours in the urine. Vanadium is probably an essential trace element, but a vanadium-deficiency disease has not been identified in humans. The estimated daily intake of the US population ranges from 10-60 micrograms V. Vanadyl sulfate is a common supplement used to enhance weight training in athletes at doses up to 60 mg/d. In vitro and animal studies indicate that vanadate and other vanadium compounds increase glucose transport activity and improve glucose metabolism. In general, the toxicity of vanadium compounds is low. Pentavalent compounds are the most toxic and the toxicity of vanadium compounds usually increases as the valence increases. Most of the toxic effects of vanadium compounds result from local irritation of the eyes and upper respiratory tract rather than systemic toxicity. The only clearly documented effect of exposure to vanadium dust is upper respiratory tract irritation characterized by rhinitis, wheezing, nasal hemorrhage, conjunctivitis, cough, sore throat, and chest pain. Case studies have described the onset of asthma after heavy exposure to vanadium compounds, but clinical studies to date have not detected an increased prevalence of asthma in workers exposed to vanadium.

Time course effects of vanadium supplement on cytosolic reduced glutathione level and glutathione S-transferase activity.

The influence of vanadium, an important dietary micronutrient, was evaluated on the cytosolic reduced glutathione (GSH) content and glutathione S-transferase (GST) activity in several rat target tissues. Supplementation of drinking water with vanadium at the level of 0.2 or 0.5 ppm for 4, 8, or 12 wk was found to increase the GSH level with a concomitant elevation in GST activity in the liver followed by small intestine mucosa, large intestine mucosa, and kidney. The results were almost dose-dependent and mostly pronounced with 0.5 ppm vanadium after 12 wk of its continuous supplementation. Neither the GSH level nor GST activity was significantly altered in forestomach and lung following vanadium supplementation throughout the study. The levels of vanadium that were found to increase the content of GSH and activity of GST in the liver, intestine, and kidney did not exert any toxic manifestation as evidenced from water and food consumption as well as the growth responses of the experimental animals. Moreover, these doses of vanadium did not impair either hepatic or renal functions as they did not alter the serum activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), sorbitol dehydrogenase (SDH), as well as serum urea and creatinine level. All these results clearly indicate that vanadium under the doses employed in our study has a significant inducing role on GSH content with a concurrent elevation in GST activity in the liver and specific extrahepatic tissues without any apparent sign of cytotoxicity. This attribute of vanadium may have a greater importance in terms of biotransformation and detoxification of xenobiotics, including carcinogens. In addition, since the ability to afford an increment in the endogenous GSH-GST pool by anticarcinogenic natural substances has been found to correlate with their activity to inhibit neoplastic transformation, the trace element vanadium may be considered as a novel anticancer agent.

Chelating agents in the treatment of acute vanadyl sulphate intoxication in mice.

Eighteen chelating or reducing agents were tested to determine their relative efficacy as antagonists in acute intramuscular vanadyl sulphate intoxication in mice. The chelating or reducing agents were administered intraperitoneally to male Swiss mice at doses equal to one-fourth of their respective LD50. Therapeutic effectiveness (TEF) was calculated. In a subsequent experiment, the effect of EDTA, glutathione, DFOA, ascorbic acid, succinic acid, monosodium phosphate, Tiron, DTPA, and 2-mercaptosuccinic acid on the excretion, and distribution of vanadium was determined. Of the compounds examined, Tiron followed by ascorbic acid, and 2-mercaptosuccinic acid were effective in increasing the urinary excretion of vanadium. Tiron, and 2-mercaptosuccinic acid were also effective in reducing the concentration of vanadium found in kidney, the main target organ of vanadium accumulation. Tiron appears to be the most effective agent of those tested in the prevention of acute vanadium (IV) intoxication in mice.

Effectiveness of chelation therapy with time after acute vanadium intoxication.

The effect of increasing the time interval between vanadium exposure and chelation therapy was studied in male Swiss mice. The following chelating or reducing agents were administered i.p. at 0, 0.5, 2 and 8 h after i.p. administration of 0.16 mmol kg-1 sodium metavanadate: ascorbic acid, deferoxamine mesylate (DFOA) and 4,5-dihydroxy-1,3-benzene-disulphonic acid (Tiron). These agents were given at doses equal to one-quarter of their respective LD50 values. Daily elimination of vanadium into urine and faeces was determined for four days. The excretion of vanadium was especially rapid in the first 24 h. Treatment with Tiron increased significantly the urinary elimination of vanadium in all four groups during Day 1, whereas DFOA significantly increased the faecal excretion during the same period. Treatment with DFOA or Tiron resulted in a significant decrease in the concentration of vanadium in the kidney four days after sodium metavanadate administration. The magnitude of the increased elimination of vanadium, as well as the decreased tissue concentration of the metal, was remarkably attenuated by increasing the time interval between vanadium injection and administration of the chelators.