Neurobehavioral effects of chronic low-dose vanadium administration in young male rats.

Exposure to the metal vanadium, in both animals and humans has been linked to various physiological consequences including respiratory and gastrointestinal conditions. Research on the neurobehavioral effects of vanadium exposure is limited. Hence, the purpose of the current study was to examine the effects of chronic low-dose vanadium administration (0.04 mg/week) on the behavior of young male rats. Four weeks following the administration of vanadium, rats were tested on the open field, object recognition, and Morris Water maze tasks. Vanadium did not affect exploration, locomotion, or anxiety-like behavior as measured by the open field task. Vanadium administration affected novel object recognition performance. Intriguingly, rats exposed to vanadium exhibited lower latency times on day 2 of the Morris Water maze. These findings suggest that vanadium's behavioral effects are complex and warrant further investigation to better understand the potential benefits and consequences of its exposure.

Vanadium Decreases Hepcidin mRNA Gene Expression in STZ-Induced Diabetic Rats, Improving the Anemic State.

Diabetes is a disease with an inflammatory component that courses with an anemic state. Vanadium (V) is an antidiabetic agent that acts by stimulating insulin signaling. Hepcidin blocks the intestinal absorption of iron and the release of iron from its deposits. We aim to investigate the effect of V on hepcidin mRNA expression and its consequences on the hematological parameters in streptozotocin-induced diabetic Wistar rats. Control healthy rats, diabetic rats, and diabetic rats treated with 1 mgV/day were examined for five weeks. The mineral levels were measured in diet and serum samples. Hepcidin expression was quantified in liver samples. Inflammatory and hematological parameters were determined in serum or whole blood samples. The inflammatory status was higher in diabetic than in control rats, whereas the hematological parameters were lower in the diabetic rats than in the control rats. Hepcidin mRNA expression was significantly lower in the V-treated diabetic rats than in control and untreated diabetic rats. The inflammatory status remained at a similar level as the untreated diabetic group. However, the hematological profile improved after the V-treatment, reaching similar levels to those found in the control group. Serum iron level was higher in V-treated than in untreated diabetic rats. We conclude that V reduces gene expression of hepcidin in diabetic rats, improving the anemic state caused by diabetes.

The impact of concomitant administration of vanadium and insulin on endothelial dysfunction markers (PAI-1 and ET-1) in type 1 diabetic rats.

Endothelial dysfunction in type 1 diabetes mellitus (T1DM) is an important factor in the pathogenesis of micro- and macrovascular complications. The present study was to investigate the impact of combined vanadium and insulin for proper control and protection against endothelial dysfunction in T1DM rats. Sixty male Sprague-Dawley rats were randomly divided into six groups; control non-treated; control vanadium treated; T1DM; T1DM + insulin; T1DM + vanadium; T1DM + insulin + vanadium treated groups. At the end of the experiment (6 weeks), serum C-reactive protein, tumour necrosis factor-alpha, IL-6, endothelin-1, plasminogen activator inhibitor-1, fasting glucose serum lipogram, liver homogenate SOD activity and MDA levels were determined. Concomitant insulin and vanadium treatment improved the diabetic metabolic disturbances in addition to endothelial dysfunction and inflammatory markers. We can conclude that concomitant administration of both vanadium and insulin in T1DM decreased the risk for the development of endothelial dysfunction, micro- and macrovascular complications.

Vanadium inhibits Type 2 diabetes mellitus-induced aortic ultrastructural alterations associated with the Inhibition of dyslipidemia and biomarkers of inflammation in rats / El vanadio inhibe las alteraciones ultraestructurales aórticas inducidas por la diabetes mellitus Tipo 2 asociadas con la inhibición de la dislipidemia y los biomarcadores de inflamación en ratas

The potential inhibitory effect of the insulin mimicking agent, vanadium on type 2 diabetes mellitus (T2DM)induced alterations to the aorta ultrastructure associated with the suppression of dyslipedima and biomarkers of inflammation has not been investigated before. Therefore, we tested whether vanadium can protect against aortic injury induced secondary to T2DM possibly via the inhibition of blood lipid and inflammatory biomarkers. T2DM was induced in rats by a high-fat diet and streptozotocin (50 mg/ kg), and the treatment group started vanadium treatment five days post diabetic induction and continued until being sacrificed at week 10. Using light and electron microscopy examinations, we observed in the model group substantial damage to the aorta tissue such as damaged endothelium, degenerative cellular changes with vacuolated cytoplasm and thickened internal elastic lamina that were substantially ameliorated by vanadium. Administration of vanadium to diabetic rats also significantly (p<0.05) reduced blood levels of glucose, hyperlipidemia and biomarkers of inflammation (TNF-a, IL-6). We conclude that vanadium protects against T2DM-induced aortic ultrastructural damage in rats, which is associated with the inhibition of blood sugar and lipid and inflammatory biomarkers.

El potencial efecto inhibidor del agente imitador de la insulina, el vanadio en las alteraciones inducidas por la diabetes mellitus tipo 2 (DM2) en la ultraestructura de la aorta, asociada con la supresión de dislipidemia y los biomarcadores de inflamación no se ha investigado anteriormente. El objetivo fue estudiar las propiedades del vanadio para proteger contra la lesión aórtica inducida a la DM2, a través de la inhibición de los lípidos sanguíneos y los biomarcadores inflamatorios. La DM2 fue inducida en ratas con una dieta alta en grasas y estreptozotocina (50 mg / kg), y el grupo de tratamiento fue sometido a un régimen continuo con vanadio, cinco días después de la inducción diabética hasta ser sacrificadas en la semana 10. Se utilizaron exámenes de luz y microscopía electrónica en el grupo modelo y se observó un daño sustancial al tejido de la aorta, como también en el endotelio; los cambios celulares degenerativos con citoplasma vacuolado y lámina elástica interna engrosada mejoró sustancialmente con vanadio. La administración de vanadio a ratas diabéticas también redujo significativamente (p <0,05) los niveles sanguíneos de la glucosa, hiperlipidemia y los biomarcadores de inflamación (TNFa, IL-6). En conclusión, el vanadio protege contra el daño ultraestructural aórtico inducido por T2DM en ratas, que es asociado con la inhibición del azúcar en la sangre y los biomarcadores de lípidos y de inflamatorios.

Bis(ethylmaltolato)oxidovanadium(iv) inhibited the pathogenesis of Alzheimer's disease in triple transgenic model mice.

Vanadium compounds have been reported to mimic the anti-diabetes effects of insulin on rodent models, but their effects on Alzheimer's disease (AD) have rarely been explored. In this paper, 9-month-old triple transgenic AD model mice (3×Tg-AD) received bis(ethylmaltolato)oxidovanadium(iv) (BEOV) at doses of 0.2 mmol L-1 (68.4 µg mL-1) and 1.0 mmol L-1 (342 µg mL-1) for 3 months. BEOV at both doses was found to improve contextual memory and spatial learning in AD mice. It also improved glucose metabolism and protected neuronal synapses in the AD brain, as evidenced respectively by 18F-labeled fluoro-deoxyglucose positron emission tomography (18F-FDG-PET) scanning and by transmission electron microscopy. Inhibitory effects of BEOV on ß-amyloid (Aß) plaques and neuronal impairment in the cortex and hippocampus of fluorescent AD mice were visualized three-dimensionally by applying optical clearing technology to brain slices before confocal laser scanning microscopy. Western blot analysis semi-quantitatively revealed the altered levels of Aß42 in the brains of wildtype, AD, and AD treated with 0.2 and 1.0 mmol L-1 BEOV mice (70.3%, 100%, 83.2% and 56.8% in the hippocampus; 82.4%, 100%, 66.9% and 42% in the cortex, respectively). The mechanism study showed that BEOV increased the expression of peroxisome proliferator-activated receptor γ (PPARγ) (140%, 100%, 142% and 160% in the hippocampus; 167%, 100%, 124% and 133% in the cortex) to inactivate the JAK2/STAT3/SOCS-1 pathway and to block the amyloidogenesis cascade, thus attenuating Aß-induced insulin resistance in AD models. BEOV also reduced protein tyrosine phosphatase 1B (PTP1B) expression (74.8%, 100%, 76.5% and 53.8% in the hippocampus; 71.8%, 100%, 94.2% and 81.8% in cortex) to promote insulin sensitivity and to stimulate the PI3K/Akt/GSK3ß pathway, subsequently reducing tau hyperphosphorylation (phosphorylated tau396 levels were 51.1%, 100%, 56.1% and 50.2% in the hippocampus; 22.2%, 100%, 36.1%, and 24% in the cortex). Our results suggested that BEOV reduced the pathological hallmarks of AD by targeting the pathways of PPARγ and PTP1B in 3×Tg AD mice.

Effect of Epigallo-Catechin-3-Gallate on Lipid Metabolism Related Gene Expression and Yolk Fatty Acid Profiles of Laying Hens Exposed to Vanadium.

As the understanding of the pathways involved in such effect are quite limited, we investigated the gene pathways that modulate lipid metabolism in layers and the fatty acid profiles of the yolk of layers that were challenged with dietary vanadium (V) and supplemented with epigallo-catechin-3-gallate (EGCG). For this purpose, a total of 120 hens were divided into four groups which were fed the following experimental diets for a period of 8 weeks: control (basal diet), V10 (control + 10 mg/kg V), EGCG130 (V10 + 130 mg/kg EGCG), and EGCG217 (V10 + 217 mg/kg EGCG). Blood total cholesterol, triglyceride, glucose, and very low-density lipoprotein-cholesterol concentration were lower in V10, EGCG130, and EGCG217 groups compared to the control group, while total cholesterol and triglyceride content in blood were lower in the EGCG217 group than in V10 group (P < 0.05). Hens consumed V10 diet had the highest triglyceride content in liver among treatments, whereas EGCG130 and EGCG217 groups had lower values when compared to those observed in the control group (P < 0.01). Dietary inclusion of V increased yolk polyunsaturated fatty acid (PUFA) and total unsaturated fatty acid (UFA) content compared to the control group (P < 0.05), whereas the addition of either 130 or 217 mg/kg EGCG in V containing diet resulted in similar yolk PUFA and UFA contents with those observed in the control group. Treatment with V alone upregulated the expression of hepatic fatty acid synthase (FAS) and sterol-regulator element-binding protein 1 (SREBP1), while EGCG downregulated FAS and SREBP1 expressions in contrast to V10 treatments (P < 0.01). Liver gene expression peroxisome proliferator-activated receptor gamma (PPARγ) was lower in the V10 than in the control group while EGCG inclusion groups upregulated their expression (P < 0.05). In conclusion, the data gathered in this study indicate that dietary V and EGCG alter the layers' lipid metabolism and fat deposition pattern in egg yolk, which might be associated with their modulatory effect on lipogenesis-related gene (FAS, SREBP1, and PPARγ) expression.

Effect of Vanadium Supplementation on Production Performance, Nutrient Utilization, Plasma Mineral Concentration, and Mineral Balance in Lactating Goats.

Vanadium (V) has not been elucidated as an essential mineral in ruminants, though in lower organisms and rat model, its role is well known as insulin-a mimetic agent for catalyzing enzymatic activities. The objective of this study was to determine the effect of V supplementation on production performance, milk composition, and mineral profile in lactating goats. Twenty-four crossbred goats (body weight 34.83 ± 0.25 kg) were blocked in four groups and randomly assigned to four treatment groups (n = 6) on body weight and milk yield basis. All the animals were kept on similar feeding regimen except that different treatment groups were supplemented with 0, 2, 4, and 6 ppm inorganic V/kg DM. Feed intake, milk yield, milk composition, nutrient utilization, minerals in plasma and milk, and their balance studies post vanadium supplementation were observed during the 150-day experimental period. V supplementation did not change dry matter intake (DMI), milk yield, and composition during the experimental period. Calcium levels in plasma were improved (P < 0.05) on vanadium supplementation. Nutrient digestibility remained similar among goats fed on basal or V-supplemented diets. Blood and milk V concentration showed a positive correlation with supplemental V levels but no difference was observed in levels of other minerals. The results of present findings indicated that up to the supplemented level, dietary inorganic V does not affect the production and mineral profile in milk and plasma.

Vanadium stimulates pepper plant growth and flowering, increases concentrations of amino acids, sugars and chlorophylls, and modifies nutrient concentrations.

Vanadium (V) can be absorbed by plants and regulate their growth and development, although contrasting effects have been reported among species and handling conditions. The objective of this work was to evaluate the beneficial effect of V on pepper plants (Capsicum annuum L.). The plants were grown in a hydroponic system with the application of four V concentrations (0, 5, 10, and 15 µM NH4VO3). Four weeks after the beginning of the treatments, growth, flowering, biomass, chlorophyll concentration, total amino acids, total soluble sugars, and nutrients were determined in leaves, stems, and roots. The application of 5 µM V increased plant growth, induced floral bud development, and accelerated flowering. The chlorophyll concentration varied according to the type of plant part analyzed. The concentrations of amino acids and sugars in leaves and roots were higher with 5 µM. With 10 and 15 µM V, the plants were smaller and showed toxicity symptoms. The K concentration in leaves decreased as the V dose increased (0 to 15 µM). However, 5 µM V increased the concentrations of N, P, K, Ca, Mg, Cu, Mn, and B, exclusively in stems. The application of 15 µM V decreased the concentrations of Mg and Mn in leaves, but increased those of P, Ca, Mg, Cu, and B in roots. We conclude that V has positive effects on pepper growth and development, as well as on the concentrations of amino acids and total sugars. V was antagonistic with K, Mg, and Mn in leaves, while in stems and roots, there was synergism with macro and micronutrients. Vanadium is a beneficial element with the potential to be used in biostimulation approaches of crops like pepper.

Vanadium quercetin complex attenuates mammary cancer by regulating the P53, Akt/mTOR pathway and downregulates cellular proliferation correlated with increased apoptotic events.

Flavonoid metal ion complexes have been deliberated in recent years and are considered as a new class of medicinal agents with enhanced therapeutic activity and low toxicity. Our study deals with chemotherapeutic effects of vanadium, when coordinated with the flavonoid quercetin on a defined model of chemically induced rat mammary carcinogenesis in vivo and on human breast cancer cell line MCF-7 in vitro. The characterization of the complex was achieved through UV-Visible, IR, and Mass spectra and antioxidant activity was assessed by DPPH, FRAP and ABTS methods. In vitro studies established that the complex upregulated the expressions of p53, Caspase 3 and 9, whereas down regulating Akt, mTOR and VEGF expressions and also induced apoptosis and DNA fragmentation in a dose dependent manner. Acute and Sub-acute toxicity was performed to determine safe doses. 7,12-Dimethylbenz(α)anthracene (0.5 mg/100 g body weight) was used for induction of breast cancer in female Sprague-Dawley rats via single tail vein injection. The histopathological analysis after 24 weeks of carcinogenesis study depicted substantial repair of hyperplastic lesions. TUNEL assay showed an increase in apoptotic index (0.14 ± 0.03; 0.15 ± 0.01) in vanadium-quercetin treated groups as compared to the carcinogen control (0.02 ± 0.01) along with upregulation of Bcl-2 and downregulation of Bax and p53. Immunohistochemical analysis also exhibited decrease in cell proliferation in the vanadium-quercetin treated groups (11.3 ± 0.12; 11.8 ± 0.10). Thus, results from both in vivo and in vitro studies revealed that vanadium-quercetin complex could be a potential candidate for development of approved drug for breast cancer in the near future.

Changes in the brain antioxidant profile after chronic vanadium administration in mice.

Vanadium is known to induce reactive oxygen species (ROS) in biological systems. Exposure to vanadium has been linked to neurological defects affecting the central nervous system (CNS) early in life and culminates later to neurodegeneration. This study was designed to evaluate the effects of chronic vanadium exposure on antioxidant profile in mice, and progressive changes after withdrawal from treatment. A total of 85 male BALB/c mice (4 weeks old) were used for the experiment and were divided into three groups of vanadium exposed (3 mg/kg i.p at 3-18 months treatment), matched controls, and animals exposed to vanadium for three months and thereafter vanadium was withdrawn. Vanadium exposure caused significant increases (p<0.05) in levels of malondialdehyde (MDA), hydrogen peroxide (H2O2) generation and nitric oxide with a concomitant decrease (p<0.05) in the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-S-transferase and a decline in the level of reduced glutathione (GSH) after 6 months of vanadium exposure in the brain. This trend continued in all vanadium-exposed groups (9, 12, 15 and 18 months) relative to the matched controls. Withdrawal after 3 months of vanadium exposure significantly reversed oxidative stress in intoxicated mice from 9 to 15 months after vanadium withdrawal. We have shown that chronic administration of vanadium led to oxidative stress in the brain which is reversible only after a long period of vanadium withdrawal.

Bis(4,4'-dimethyl-2,2'-bipyridine)oxidovanadium(IV) Sulfate Dehydrate: Potential Candidate for Controlling Lipid Metabolism?

Vanadium is a trace element mainly connected with regulation of insulin metabolism which is particularly important in diabetes. In recent years, organic complexes of vanadium seem to be more interesting than inorganic salts. Nevertheless, the effect of vanadium on lipid metabolism is still a problematic issue; therefore, the main purpose of this study was to investigate the effect of 3 organic complexes of vanadium such as sodium (2,2'-bipyridine)oxidobisperoxovanadate(V) octahydrate, bis(2,2'-bipyridine)oxidovanadium(IV) sulfate dehydrate, and bis(4,4'-dimethyl-2,2'-bipyridine)oxidovanadium(IV) sulfate dihydrate in conjunction with high-fat as well as control diet in nondiabetes model on the following lipid parameters: total cholesterol, triglycerides, and high density lipoprotein as well as activity of paraoxonase 1. All of these parameters were determined in plasma of Wistar rats. The most significant effect was observed in case of bis(4,4'-dimethyl-2,2' bipyridine)oxidovanadium(IV) sulfate dehydrate in rats fed with high-fat diet. Based on our research, bis(4,4'-dimethyl-2,2'-bipyridine)oxidovanadium(IV) sulfate dihydrate should be the aim of further research and perhaps it will be an important factor in the regulation of lipid metabolism.

Ameliorated Effects of (-)-Epigallocatechin Gallate Against Toxicity Induced by Vanadium in the Kidneys of Wistar Rats.

The aim of the study was to assess the protective effect of (-)-epigallocatechin gallate (EGCG), a flavonoid abundant in green tea, against ammonium metavanadate (AMV)-induced oxidative stress in male Wistar rats. Four groups of animals have been used, a control group and three test groups. In the first test group, AMV was intra-peritoneally (i.p) injected daily (5 mg/kg body weight for five consecutive days). The second test group of animals was also injected daily with EGCG (5 mg/kg body weight) during the same period. However, the third test group was i.p. injected with both AMV and EGCG (5 mg/kg body weight for five consecutive days). When given alone, AMV induced an oxidative stress evidenced by an increase of lipid peroxidation levels (expressed as TBARS concentration) in kidney. In these animals, activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were significantly decreased, suggesting significant reduction of the antioxidant defense system at the cell level. Kidney histological sections, showed glomerular hypertrophy and tubular dilatation. In AMV-treated animals receiving EGCG, the oxidative stress was much less pronounced and activities of antioxidant enzymes were kept close to control values. Histopathological changes were less prominent. Our results confirm that green tea and other sources of flavonoids might confer a strong protection against ammonium metavanadate-induced oxidative stress.

Effects of local vanadium delivery on diabetic fracture healing.

This study evaluated the effect of local vanadyl acetylacetonate (VAC), an insulin mimetic agent, upon the early and late parameters of fracture healing in rats using a standard femur fracture model. Mechanical testing, and radiographic scoring were performed, as well as histomorphometry, including percent bone, percent cartilage, and osteoclast numbers. Fractures treated with local 1.5 mg/kg VAC possessed significantly increased mechanical properties compared to controls at 6 weeks post-fracture, including increased torque to failure (15%; p = 0.046), shear modulus (89%; p = 0.043), and shear stress (81%; p = 0.009). The radiographic scoring analysis showed increased cortical bridging at 4 weeks and 6 weeks (119%; p = 0.036 and 209%; p = 0.002) in 1.5 mg/kg VAC treated groups. Histomorphometry of the fracture callus at days 10 and 14 showed increased percent cartilage (121%; p = 0.009 and 45%; p = 0.035) and percent mineralized tissue (66%; p = 0.035 and 58%; p = 0.006) with local VAC treated groups compared to control. Additionally, fewer osteoclasts were observed in the local VAC treated animals as compared to controls at day 14 (0.45% ± 0.29% vs. 0.83% ± 0.36% of callus area; p = 0.032). The results suggest local administration of VAC acts to modulate osteoclast activity and increase percentage of early callus cartilage, ultimately enhancing mechanical properties comparably to non-diabetic animals treated with local VAC. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2174-2180, 2017.

Effect of Feeding and Withdrawal of Vanadium and Vitamin C on Egg Quality and Vanadium Residual Over Time in Laying Hens.

This experiment examined the egg quality of hens fed vanadium (V) and vitamin C (VC) during storage, as well as the V and VC withdrawal on egg quality and V residual in egg. A total of 360 laying hens (31 weeks old) were randomly allotted into a 3 × 2 factorial arrangement treatments (6 replicates and 10 chicks per replicate) with three levels of dietary V (0, 5, and 10 mg/kg) and two levels of VC (0 and 100 mg/kg) for 19 weeks (feeding V and VC 12 weeks, recovery 7 weeks). The V residual in eggs at 4, 8, and 12th weeks were increased (linear effect, P ≤ 0.01) as V levels increased and was not detected in albumen at 7th week after V withdrawal. Followed by 12-week feeding period, albumen height and Haugh unit of eggs during 2-week storage were decreased (linear and quadratic effect, P < 0.01) by dietary V supplementation. Lightness value was increased (linear effect, P < 0.01), whereas redness and yellowness value of the eggshell were lowered (linear effect, P < 0.01) in V-containing diet. During 7-week withdrawal period, eggs from groups pre-feeding 5 and 10 mg/kg V had lower (linear effect, P < 0.01) overall albumen height and Haugh unit. The reducing effect on albumen height and HU continued to be observed until the seventh week, whereas the bleaching effect on eggshell color disappeared after 1-week withdrawal. The results indicated that feeding 5 or 10 mg/kg V increases egg V residual and reduces egg albumen quality and bleached the shell color, and the impaired albumen quality induced by 10 mg/kg of V lasted at least 6 weeks after changing to no V supplementation diet. The addition of VC did not show to affect egg quality during storage or recovery phase.

Regional Myelin and Axon Damage and Neuroinflammation in the Adult Mouse Brain After Long-Term Postnatal Vanadium Exposure.

Environmental exposure to vanadium occurs in areas of persistent burning of fossil fuels; this metal is known to induce oxidative stress and oligodendrocyte damage. Here, we determined whether vanadium exposure (3 mg/kg) in mice during the first 3 postnatal months leads to a sustained neuroinflammatory response. Body weight monitoring, and muscle strength and open field tests showed reduction of body weight gain and locomotor impairment in vanadium-exposed mice. Myelin histochemistry and immunohistochemistry for astrocytes, microglia, and nonphosphorylated neurofilaments revealed striking regional heterogeneity. Myelin damage involved the midline corpus callosum and fibers in cortical gray matter, hippocampus, and diencephalon that were associated with axonal damage. Astrocyte and microglial activation was identified in the same regions and in the internal capsule; however, no overt myelin and axon damage was observed in the latter. Double immunofluorescence revealed induction of high tumor necrosis factor (TNF) immunoreactivity in reactive astrocytes. Western blotting analysis showed significant induction of TNF and interleukin-1ß expression. Together these findings show that chronic postnatal vanadium exposure leads to functional deficit and region-dependent myelin damage that does not spare axons. This injury is associated with glial cell activation and proinflammatory cytokine induction, which may reflect both neurotoxic and neuroprotective responses.

Enrichment, Distribution of Vanadium-Containing Protein in Vanadium-Enriched Sea Cucumber Apostichopus japonicus and the Ameliorative Effect on Insulin Resistance.

Sea cucumbers are a potential source of natural organic vanadium that may improve insulin resistance. In this work, vanadium was accumulated rapidly in blood, body wall, and intestine by sea cucumber Apostichopus japonicus. Furthermore, water-soluble vanadium-containing proteins, the main form of the organic vanadium, were tentatively accumulated and isolated by a bioaccumulation experiment. It was also designed to evaluate the beneficial effect of vanadium-containing proteins (VCPs) from sea cucumber rich in vanadium on the development of hyperglycemia and insulin resistance in C57BL/6J mice fed with a high-fat high-sucrose diet (HFSD). HFSD mice treated with VCPs significantly decreased fasting blood glucose, serum insulin, and HOMA-IR values as compared to HFSD mice, respectively. Serum adiponectin, resistin, TNF-α, and leptin levels in insulin-resistant mice were dramatically reduced by a VCP supplement. These results show an ameliorative effect on insulin resistance by treatment with VCPs. Such compound seems to be a valuable therapy to achieve and/or maintain glycemic control and therapeutic agents in the treatment arsenal for insulin resistance and type 2 diabetes.

Quantitative Assessment of Proliferative Effects of Oral Vanadium on Pancreatic Islet Volumes and Beta Cell Numbers of Diabetic Rats.

BACKGROUND: Oral vanadyl sulfate (vanadium) induces normoglycemia, proliferates beta cells and prevents pancreatic islet atrophy in streptozotocin-induced diabetic rats. Soteriological method is used to quantitate the proliferative effects of vanadium on beta-cell numbers and islet volumes of normal and diabetic rats. METHODS: Adult male Sprague-Dawley rats were made diabetic with intravenous streptozotocin injection (40 mg/kg). Normal and diabetic rats were divided into four groups. While control normal and diabetic (CD) groups used water, vanadium-treated normal (VTN) and diabetic (VTD) groups used solutions containing vanadyl sulfate (0.5-1 mg/mL, VOSO4+5H2O). Tail blood samples were used to measure blood glucose (BG) and plasma insulin. Two months after treatment, rats were sacrificed, pancreata prepared, and stereology method was used to quantitatively evaluate total beta cell numbers (TBCN) and total islet volumes (TISVOL). RESULTS: Normoglycemia persisted in VTN with significantly decreased plasma insulin (0.19±0.08 vs. 0.97±0.27 ng/dL, P<0.002). The respective high BG (532±49 vs. 144±46 mg/dL, P<0.0001) and reduced plasma insulin (0.26±0.15 vs. 0.54±0.19 ng/dL, P<0.002) seen in CD were reversed in VTD during vanadium treatment or withdrawal. While the induction of diabetes, compared to their control, significantly decreased TISVOL (1.9±0.2 vs. 3.03±0.6 mm3, P<0.003) and TBCN (0.99±0.1 vs. 3.2±0.2 x 106, P<0.003), vanadium treatment significantly increased TISVOL (2.9±0.8 and 4.07±1.0 mm3, P<0.003) and TBCN (1.5±0.3 and 3.8±0.6 x 106, P<0.03). CONCLUSION: Two-month oral vanadium therapy in STZ-diabetic rats ameliorated hyperglycemia by partially restoring plasma insulin. This action was through proliferative actions of vanadium in preventing islet atrophy by increasing beta-cell numbers.

Effects of vanadium complexes supplementation on V, Cu, Mn, K, Fe, Zn, and Ca concentration in STZ diabetic rats pancreas.

The objective of the study was to assess the effects of Na[V(V)O(O2)2(2,2'-bpy)] x 8 H2O (complex 1), Na[V(V)O(O2)2(1,10'-phen)] x 5 H2O (complex 2), Na[V(V)O(O2)2(4,4'-Me-2,2'-bpy)] x 8 H2O (complex 3), [V(V)O(SO,)(1,10'-phen)] x 2 H2O, (complex 4), [V(IV)O(SO4)(2,2'-bpy)] x H2O (complex 5), where: 2,2'-bpy = 2,2'-bipyridine, 1.10'-phen = 1,10'-phenanthroline, 4,4'-Me-2,2'-bpy = 4,4'-dimethyl-2,2'-bipyridine and a small insulin injection on V, Cu, Mn, K, Fe, Zn, and Ca concentration in the STZ (streptozotocin) diabetic rats pancreas during a 5-week treatment with the tested complexes. In all groups of animals metal concentration in the pancreas was investigated by means of Proton Induced X-ray Emission (PIXE) method. Maximum concentration of vanadium was observed in the pancreas for complex 5 (1.69 +/- 0.09 mg/kg dry weight), lower for complex 3 (1.51 +/- 0.10 mg/kg dry weight), and the lowest for complex 1 (1.21 +/- 0.27 mg/kg dry weight) supplementation. The influence of vanadium administration on other metals' concentration in the rats' pancreas was also investigated. All vanadium-tested complexes showed an increase of zinc concentration in the examined pancreas in comparison to the diabetic animals not treated with vanadium. The results were the highest for complex 1 and the lowest for complex 5. The concentration of Fe, Cu, Mn, K and Ca in the pancreas is not evidently influenced by administration of the vanadium complexes.

Reactivity-activity relationships of oral anti-diabetic vanadium complexes in gastrointestinal media: an X-ray absorption spectroscopic study.

The reactions of oral V(V/IV) anti-diabetic drugs within the gastrointestinal environment (particularly in the presence of food) are a crucial factor that affects their biological activities, but to date these have been poorly understood. In order to build up reactivity-activity relationships, the first detailed study of the reactivities of typical V-based anti-diabetics, Na3V(V)O4 (A), [V(IV)O(OH2)5](SO4) (B), [V(IV)O(ma)2] (C, ma = maltolato(-)) and (NH4)[V(V)(O)2(dipic)] (D, dipic = pyridine-2,5-dicarboxylato(2-)) with simulated gastrointestinal (GI) media in the presence or absence of food components has been performed by the use of XANES (X-ray absorption near edge structure) spectroscopy. Changes in speciation under conditions that simulate interactions in the GI tract have been discerned using correlations of XANES parameters that were based on a library of model V(V), V(IV), and V(III) complexes for preliminary assessment of the oxidation states and coordination numbers. More detailed speciation analyses were performed using multiple linear regression fits of XANES from the model complexes to XANES obtained from the reaction products from interactions with the GI media. Compounds B and D were relatively stable in the gastric environment (pH ∼ 2) in the absence of food, while C was mostly dissociated, and A was converted to [V10O28](6-). Sequential gastric and intestinal digestion in the absence of food converted A, B and D to poorly absorbed tetrahedral vanadates, while C formed five- or six-coordinate V(V) species where the maltolato ligands were likely to be partially retained. XANES obtained from gastric digestion of A-D in the presence of typical food components converged to that of a mixture of V(IV)-aqua, V(IV)-amino acid and V(III)-aqua complexes. Subsequent intestinal digestion led predominantly to V(IV) complexes that were assigned as citrato or complexes with 2-hydroxyacidato donor groups from other organic compounds, including certain carbohydrates. The absence of strong reductants (such as ascorbate) in the food increased the V(V) component in gastrointestinal digestion products. These results can be used to predict the oral bioavailability of various types of V(V/IV) anti-diabetics, and the effects of taking such drugs with food.

The protective effect of vanadium against diabetic cataracts in diabetic rat model.

The present study was designed to investigate the effect of vanadium in alloxan-induced diabetes and cataract in rats. Different doses of vanadium was administered once daily for 8 weeks to alloxan-induced diabetic rats. To know the mechanism of action of vanadium, lens malondialdehyde (MDA), protein carbonyl content, activity of superoxide dismutase (SOD), activities of aldose reductase (AR), and sorbitol levels were assayed, respectively. Supplementation of vanadium to alloxan-induced diabetic rats decreased the blood glucose levels due to hyperglycemia, inhibited the AR activity, and delayed cataract progression in a dose-dependent manner. The observed beneficial effects may be attributed to polyol pathway activation but not decreased oxidative stress. Overall, the results of this study demonstrate that vanadium could effectively reduce the alloxan-induced hyperglycemia and diabetic cataracts in rats.