Histological and Memory Alterations in an Innovative Alzheimer's Disease Animal Model by Vanadium Pentoxide Inhalation.

Background: Previous work from our group has shown that chronic exposure to Vanadium pentoxide (V2O5) causes cytoskeletal alterations suggesting that V2O5 can interact with cytoskeletal proteins through polymerization and tyrosine phosphatases inhibition, causing Alzheimer's disease (AD)-like hippocampal cell death. Objective: This work aims to characterize an innovative AD experimental model through chronic V2O5 inhalation, analyzing the spatial memory alterations and the presence of neurofibrillary tangles (NFTs), amyloid-ß (Aß) senile plaques, cerebral amyloid angiopathy, and dendritic spine loss in AD-related brain structures. Methods: 20 male Wistar rats were divided into control (deionized water) and experimental (0.02 M V2O5 1 h, 3/week for 6 months) groups (n = 10). The T-maze test was used to assess spatial memory once a month. After 6 months, histological alterations of the frontal and entorhinal cortices, CA1, subiculum, and amygdala were analyzed by performing Congo red, Bielschowsky, and Golgi impregnation. Results: Cognitive results in the T-maze showed memory impairment from the third month of V2O5 inhalation. We also noted NFTs, Aß plaque accumulation in the vascular endothelium and pyramidal neurons, dendritic spine, and neuronal loss in all the analyzed structures, CA1 being the most affected. Conclusions: This model characterizes neurodegenerative changes specific to AD. Our model is compatible with Braak AD stage IV, which represents a moment where it is feasible to propose therapies that have a positive impact on stopping neuronal damage.

Metabolic alterations and mitochondrial dysfunction in human airway BEAS-2B cells exposed to vanadium pentoxide.

Vanadium pentoxide (V+5) is a hazardous material that has drawn considerable attention due to its wide use in industrial sectors and increased release into environment from human activities. It poses potential adverse effects on animals and human health, with pronounced impact on lung physiology and functions. In this study, we investigated the metabolic response of human bronchial epithelial BEAS-2B cells to low-level V+5 exposure (0.01, 0.1, and 1 ppm) using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Exposure to V+5 caused extensive changes to cellular metabolism in BEAS-2B cells, including TCA cycle, glycolysis, fatty acids, amino acids, amino sugars, nucleotide sugar, sialic acid, vitamin D3, and drug metabolism, without causing cell death. Altered mitochondrial structure and function were observed with as low as 0.01 ppm (0.2 µM) V+5 exposure. In addition, decreased level of E-cadherin, the prototypical epithelial marker of epithelial-mesenchymal transition (EMT), was observed following V+5 treatment, supporting potential toxicity of V+5 at low levels. Taken together, the present study shows that V+5 has adverse effects on mitochondria and the metabolome which may result in EMT activation in the absence of cell death. Furthermore, results suggest that high-resolution metabolomics could serve as a powerful tool to investigate metal toxicity at levels which do not cause cell death.

Identification of Potential Artefacts in In Vitro Measurement of Vanadium-Induced Reactive Oxygen Species (ROS) Production.

We investigated vanadium, i.e., a redox-active heavy metal widely known for the generation of oxidative stress in cultured mammalian cells, to determine its ability to interfere with common oxidative stress-related bioassays in cell-free conditions. We first assessed the prooxidant abilities (H2O2 level, oxidation of DHR 123, and DCFH-DA dyes) and antioxidant capacity (ABTS, RP, OH, and DPPH methods) of popular mammalian cell culture media, i.e., Minimal Essential Medium (MEM), Dulbecco's Minimal Essential Medium (DMEM), Dulbecco's Minimal Essential Medium-F12 (DMEM/F12), and RPMI 1640. Out of the four media studied, DMEM has the highest prooxidant and antioxidant properties, which is associated with the highest concentration of prooxidant and antioxidant nutrients in its formulation. The studied vanadium compounds, vanadyl sulphate (VOSO4), or sodium metavanadate (NaVO3) (100, 500, and 1000 µM), either slightly increased or decreased the level of H2O2 in the studied culture media. However, these changes were in the range of a few micromoles, and they should rather not interfere with the cytotoxic effect of vanadium on cells. However, the tested vanadium compounds significantly stimulated the oxidation of DCFH-DA and DHR123 in a cell-independent manner. The type of the culture media and their pro-oxidant and antioxidant abilities did not affect the intensity of oxidation of these dyes by vanadium, whereas the vanadium compound type was important, as VOSO4 stimulated DCFH-DA and DHR oxidation much more potently than NaVO3. Such interactions of vanadium with these probes may artefactually contribute to the oxidation of these dyes by reactive oxygen species induced by vanadium in cells.

Phytotoxicity of VO2 nanoparticles with different sizes to pea seedlings.

Vanadium dioxide nanoparticles (VO2 NPs) have been massively produced due to their excellent metal-insulator transition characteristics for various applications. Pilot studies indicated the toxicity of VO2 NPs to bacteria and mammalian cells, but the environmental hazards of VO2 NPs to plants have been unrevealed to date. In this study, we reported the inhibitive effects of VO2 NPs to the growth and photosynthesis of pea seedlings. Laboratory synthesized monoclinic VO2 NPs (N-VO2), commercial nanosized VO2 NPs (S-VO2), and commercial microsized VO2 particles (M-VO2) were carefully characterized for environmental toxicity evaluations. VO2 particles were supplemented to culture medium for seed germination and seedling growth. All three VO2 samples did not affect the germination rates of pee seeds, while serious growth inhibition of pea seedlings was observed at 10 mg/L for S-VO2 and N-VO2, and 100 mg/L for M-VO2. VO2 particles had no impact on the chlorophyll contents, but the photosynthesis of leaf was significantly decreased following the consequence of N-VO2 > S-VO2 > M-VO2. The inhibition of photosynthesis was attributed to the damage of acceptor side of photosystem II by VO2 particles at high concentrations. Abundant bioaccumulations of vanadium in roots aroused oxidative damage and changed the root structure. Our results collectively indicated that the phytotoxicity of VO2 NPs was related to the concentration, size and crystalline degree.

Cytotoxicity and genotoxicity of low-dose vanadium dioxide nanoparticles to lung cells following long-term exposure.

Vanadium dioxide nanoparticles (VO2 NPs) have been massively produced and widely applied due to their excellent metal-insulator transition property, making it extremely urgent to evaluate their safety, especially for low-dose long-term respiratory occupational exposure. Here, we report a comprehensive cytotoxicity and genotoxicity study on VO2 NPs to lung cell lines A549 and BEAS-2B following a long-term exposure. A commercial VO2 NP, S-VO2, was used to treat BEAS-2B (0.15-0.6 µg/mL) and A549 (0.3-1.2 µg/mL) cells for four exposure cycles, and each exposure cycle lasted for 4 consecutive days; then various bioassays were performed after each cycle. Significant proliferation inhibition was observed in both cell lines after long-term exposure of S-VO2 at low doses that did not cause apparent acute cytotoxicity; however, the genotoxicity of S-VO2, characterized by DNA damage and micronuclei, was only observed in A549 cells. These adverse effects of S-VO2 were exposure time-, dose- and cell-dependent, and closely related to the solubility of S-VO2. The oxidative stress in cells, i.e., enhanced reactive oxygen species (ROS) generation and suppressed reduced glutathione, was the main toxicity mechanism of S-VO2. The ROS-associated mitochondrial damage and DNA damage led to the genotoxicity, and cell proliferation retard, resulting in the cellular viability loss. Our results highlight the importance and urgent necessity of the investigation on the long-term toxicity of VO2 NPs.

Effects of Vanadium Inhalation and Sweetened Beverage Ingestion in Mice: Morphological and Biochemical Changes in the Liver.

The aim of this report was to evaluate the morphological and biochemical changes in the liver by the inhalation of vanadium and consumption of sweetened beverages in a subchronic murine model. Forty CD-1 male mice were randomly divided into four groups: control, vanadium (V), sucrose 30% (S), and vanadium-sucrose (V + S). V was inhaled (1.4 mg/m3) for 1h, twice/week; 30% sucrose solution was given orally ad libitum. Blood samples were obtained for AST, ALT, and LDH determination. Liver samples were processed for histological and oxidative stress immunohistochemical evaluation with 4-hydroxynonenal at weeks 4 and 8 of exposure. Regarding liver function tests, a statistically significant increase (P < 0.05) was observed in groups V, S, and V + S at weeks 4 and 8 compared to the control group. A greater number of hepatocytes with meganuclei and binuclei were observed in V and V + S at week 8 compared to the other groups. Steatosis and regenerative changes were more extensive in the eighth week V + S group. 4-Hydroxynonenal immunoreactivity increased in the V + S group at both exposure times compared to the other groups; however, the increment was more evident in the V + S group at week 4 compared to the V + S group at week 8. An increase in De Ritis ratio (>1) was noticed in experimental groups at weeks 4 and 8. Findings demonstrate that in the liver, V, S, and V + S induced oxidative stress and regenerative changes that increased with the length of exposure. Results support possible potentiation of liver damage in areas with high air pollution and high-sweetened beverage consumption.

Internal dose of vanadium in rats following repeated exposure to vanadyl sulfate and sodium orthovanadate via drinking water.

Vanadium is a ubiquitous environmental contaminant that exists in multiple oxidation states. Humans are exposed to vanadyl (V4+) and vanadate (V5+) from dietary supplements, food, and drinking water and hence there is a concern for adverse human health. The current investigation is aimed at identifying vanadium oxidation states in vitro and in vivo and internal concentrations following exposure of rats to vanadyl sulfate (V4+) or sodium metavanadate (V5+) via drinking water for 14 d. Investigations in simulated gastric and intestinal fluids showed that V4+ was stable in gastric fluid while V5+ was stable in intestinal fluid. Analysis of rodent plasma showed that the only vanadium present was V4+, regardless of the exposed compound suggesting conversion of V5+ to V4+ in vivo and/or instability of V5+ species in biological matrices. Plasma, blood, and liver concentrations of total vanadium, after normalizing for vanadium dose consumed, were higher in male and female rats following exposure to V5+ than to V4+. Following exposure to either V4+ or V5+, the total vanadium concentration in plasma was 2- to 3-fold higher than in blood suggesting plasma as a better matrix than blood for measuring vanadium in future work. Liver to blood ratios were 4-7 demonstrating significant tissue retention following exposure to both compounds. In conclusion, these data point to potential differences in absorption and disposition properties of V4+ and V5+ salts and may explain the higher sensitivity in rats following drinking water exposure to V5+ than V4+ and highlights the importance of internal dose determination in toxicology studies.

Vanadium adversely affects sperm motility and capacitation status via protein kinase A activity and tyrosine phosphorylation.

Vanadium is a chemical element that enters the atmosphere via anthropogenic pollution. Exposure to vanadium affects cancer development and can result in toxic effects. Multiple studies have focused on vanadium's detrimental effect on male reproduction using conventional sperm analysis techniques. This study focused on vanadium's effect on spermatozoa following capacitation at the molecular level, in order to provide a more detailed assessment of vanadium's reproductive toxicity. We observed a decrease in germ cell density and a structural collapse of the testicular organ in seminiferous tubules during vanadium treatment. In addition, various sperm motion parameters were significantly decreased regardless of capacitation status, including sperm motility, rapid sperm motility, and progressive sperm motility. Curvilinear velocity, straight-line velocity, average path velocity, beat cross frequency, and mean amplitude of head lateral displacement were also decreased after capacitation. Capacitation status was altered after capacitation. Vanadium dramatically enhanced protein kinase A (PKA) activity and tyrosine phosphorylation. Taken together, our results suggest that vanadium is detrimental to male fertility by negatively influencing sperm motility, motion kinematics, and capacitation status via abnormal PKA activity and tyrosine phosphorylation before and after capacitation.

On the Capability of Oxidovanadium(IV) Derivatives to Act as All-Around Catalytic Promoters Since the Prebiotic World.

For a long time the biological role of vanadium was not known, while now the possibility of using its derivatives as potential therapeutic agents has given rise to investigations on their probable side effects. Vanadium compounds may inhibit different biochemical processes and lead to a variety of toxic effects and serious diseases. But, on the other hand, vanadium is an essential element for life. In recent years, increasing evidence has been acquired on the possible roles of vanadium in the higher forms of life. Despite several biochemical and physiological functions that have been suggested for vanadium and notwithstanding the amount of the knowledge so far accumulated, it still does not have a clearly defined role in the higher forms of life. What functions could vanadium or its very stable oxidovanadium(IV) derivatives have had in the prebiotic world and in the origins of life? In this review, we have briefly tried to highlight the most useful aspects that can be taken into consideration to give an answer to this still unresolved question and to show the high versatility of the oxidovanadium(IV) group to act as promoter of several oxidation reactions when coordinated with a variety of ligands, including diketones like acylpyrazolones.

The limitations of using the NTP chronic bioassay on vanadium pentoxide in risk assessments.

Regulatory interest in assessing the health effects of vanadium compounds is hindered by the limited chronic toxicity data available. The National Toxicology Program (NTP) conducted a robust chronic inhalation bioassay of crystalline vanadium pentoxide (V2O5), but this study has noteworthy limitations. Multiple dose range-finding studies were conducted at two separate laboratories that showed cross-laboratory differences in lung pathology (inflammation) in both species and likely complicated dose-selection. In mice, the only tissue pathology (inflammation and tumors) was at the site of entry, the respiratory system. Although significantly different from control, because lung tumor incidences were at a maximal level across all concentrations tested, the ability to extrapolate risks to the public is problematic. In rats, lung inflammation and vanadium lung burdens were comparable to those of mice, but lung tumorigenicity was not substantiated, further raising questions about appropriate species extrapolation. Open questions also exist regarding test material chemical characterization, as the laboratory relied on vanadium measurement in test chambers as a surrogate for V2O5. In sum, the NTP V2O5 study does not provide an appropriate dataset for purposes of classification and risk assessment. Additional repeat exposure studies of vanadium compounds are needed and recommendations for future studies are provided.

In vitro effect of vanadyl sulfate on cultured primary astrocytes: cell viability and oxidative stress markers.

Exposure to vanadium has been associated with deleterious effects on the central nervous system in animals and humans. Although vanadium-derived pro-oxidant species were reported to be involved in vanadium-mediated neurotoxicity, the ability of this metal to induce oxidative stress markers in glial cells remains to be elucidated. In this study, we investigated the cytotoxicity and the generation of reactive oxygen species (ROS) and nitric oxide (NO) by mouse primary astrocytes after treatment with vanadyl sulfate (VOSO4 ) at concentrations of 20, 50, 100, 200, and 500 µM. The resazurin assay revealed that treatment with VOSO4 for 24 and 48 h at concentrations of 50 and 100 µM, respectively, or higher substantially induced astrocytic cytotoxicity. Intracellular ROS increased after 6-h exposure to the lowest concentration tested (20 µM VOSO4 ) and tended to intensify after 24- and 48-h treatments reaching significant values for 20 and 500 µM VOSO4 . In turn, NO production in the examined cells was elevated after exposure to all concentrations at the 6-, 24-, and 48-h incubation periods. Our study demonstrated the ability of VOSO4 to induce H2 O2 generation in cell-free DMEM/F12 medium. The H2 O2 levels were in the micromolar range (up to 5 µM) and were detected mostly during the first few minutes after VOSO4 addition, suggesting that the generated H2 O2 could not induce toxic effects on the cells. Taken together, these results show VOSO4 induced cytotoxicity in primary astrocyte cells, which may have resulted from vanadyl-stimulated intracellular ROS and NO generation in these cells.

Cytotoxicity of vanadium oxide nanoparticles and titanium dioxide-coated vanadium oxide nanoparticles to human lung cells.

Due to excellent metal-insulator transition property, vanadium dioxide nanoparticles (VO2 NPs)-based nanomaterials are extensively studied and applied in various fields, and thus draw safety concerns of VO2 NPs exposure through various routes. Herein, the cytotoxicity of VO2 NPs (N-VO2 ) and titanium dioxide-coated VO2 NPs (T-VO2 ) to typical human lung cell lines (A549 and BEAS-2B) was studied by using a series of biological assays. It was found that both VO2 NPs induced a dose-dependent cytotoxicity, and the two cell lines displayed similar sensitivity to VO2 NPs. Under the same conditions, T-VO2 NPs showed slightly lower cytotoxicity than N-VO2 in both cells, indicating the surface coating of titanium dioxide mitigated the toxicity of VO2 NPs. Titanium dioxide coating changed the surface property of VO2 NPs and reduced the vanadium release of particles, and thus helped lowing the toxicity of VO2 NPs. The induced cell viability loss was attributed to apoptosis and proliferation inhibition, which were supported by the assays of apoptosis, mitochondrial membrane damage, caspase-3 level, and cell cycle arrest. The oxidative stress, i.e., enhanced reactive oxygen species generation and suppressed reduced glutathione , in A549 and BEAS-2B cells was one of the major mechanisms of the cytotoxicity of VO2 NPs. These findings provide safety guidance for the practical applications of vanadium dioxide-based materials.

Nitrogen-doped carbon dots-V2O5 nanobelts sensing platform for sensitive detection of ascorbic acid and alkaline phosphatase activity.

In this work, the as-prepared V2O5 nanobelts can sensitively quench the fluorescence of nitrogen-doped carbon dots (N-CDs) based on the inner filter effect (IFE). In the presence of ascorbic acid (AA), the fluorescence of N-CDs can recover through the redox reaction between V2O5 nanobelts and AA. Meanwhile, in the presence of both alkaline phosphatase (ALP) and ascorbyl-2-phosphate (AAP), the fluorescence of N-CDs can also restore since AAP can be hydrolyzed into AA by ALP. Under optimum conditions, the linear range for AA is from 0.01 to 2.5 µM with a detection limit of 3 nM and that for ALP is from 0.1 to 30 U/L with a detection limit of 0.04 U/L (S/N = 3). Particularly, the proposed probe could be successfully used to detect AA and ALP in human serum samples. Furthermore, N-CDs can be applied in fluorescence imaging of Human breast cancer cells with satisfactory results.

Vanadium-basidiomycete fungi interaction and its impact on vanadium biogeochemistry.

Fungi are well known to strongly interact with metals, thereby influencing metal biogeochemistry in the terrestrial environment. To assess and quantify potential fungi-vanadium (V) interactions, Amanita muscaria, Armillaria cepistipes, Xerocomus badius and Bjerkandera adusta were cultured in media containing soluble V (VOSO4 or NaVO3) or solid-phase V of different chemical forms and oxidation state (V2O3, VO2, V2O5, or V-Ti magnetite slag). All fungi underwent physiological and structural changes, as revealed by alterations in FT-IR peak positions and intensities relative to the control, and morphological changes of mycelia, as observed by scanning electron microscopy. The diametric growth size generally decreased with decreasing oxidation state of V and with increasing concentrations of VOSO4 and NaVO3, implying that V toxicity is dependent on V speciation. The tolerance index, the ratio of treated and control mycelium (dry weight), shows different tendencies, suggesting additional factors influencing fungi weight, such as the formation of extrahyphal crystals. Vanadium accumulation from VOSO4 and NaVO3 medium in all fungi (up to 51.3 mg g-1) shows the potential of fungi to immobilise soluble V, thereby reducing its impacts on environmental and human health. Uptake and accumulation of V in slag was insignificant, reflecting the association of slag V with insoluble crystalline materials. The fungal accumulation of V in medium amended with V-oxides demonstrates the ability of fungi to solubilise solid-phase V compounds, thereby introducing previously immobile V into the V biogeochemical cycle and into the food chain where it may impact ecological and human health. A.muscaria lowered the pH of the medium substantially during cultivation, indicating acidolysis and complexolysis via excretion of organic acids (e.g. oxalic acid). Oxidation of VOSO4 was observed by a colour change of the medium to yellow during B. adusta cultivation, revealing the role of fungally-mediated redox transformation in V (im)mobilisation. The calculated removal efficiencies of soluble V were 40-90% for A. cepistipes and X. badius, but a much lower recovery (0-20%) was observed from V oxides and slag (0-20%) by all fungi. This suggests the probable application of fungi for bio-remediation of mobile/soluble V in contaminated soils but not of V incorporated in the lattice of soil minerals.

The detoxification effect of liquid digestate on vanadium toxicity to seed germination and seedling growth of dog's tail grass.

Dog's tail grass (Setaria viridis) presented strong tolerance and high accumulation of vanadium in field conditions. Liquid digestate containing high levels of nutrients could alleviate vanadium toxicity and accelerate the growth of dog's tail grass. To elucidate the detoxification potential and mechanism of liquid digestate, dog's tail grass was grown in soil solution containing 0.14-55.8 mg L-1 of vanadium. Parameters including germination index (GI), tolerance index (TI), seedlings' fresh weight, seedlings' vanadium accumulation, antioxidant enzymes activity, malonaldehyde (MDA) content, and V5+ species, were measured after addition of 1%, 5%, 10% and 15% liquid digestate. The results showed that a vanadium level of 10.9 mg L-1was a threshold value for toxicity; furthermore, the GI and TI decreased by 50% when vanadium content reached 36.8 mg L-1. The MDA content was reduced, and the other parameters were markedly enhanced, after addition of 5% and 10% liquid digestate with vanadium levels above 36.8 mg L-1. V5+ species was the dominant vanadium species in solution and the addition of liquid digestate reduced V5+ concentrations. The detoxification of vanadium by liquid digestate was a combined effect of direct reduction of V5+ species and plant nutrition.

Genotoxic And Cytotoxic Effects Of Oral Vanadyl Sulphate.

BACKGROUND: Vanadyl sulphate is available as herbal medicine against diabetes mellitus and body building supplement, over the counter worldwide. The available data on its safety is controversial and inadequate. The objective of this study was to analyse its safety in usual therapeutic dose range. METHODS: It was an experimental study carried out at the Department of Biochemistry & Molecular Biology, Army Medical College, National University of Medical Sciences (NUMS), Rawalpindi, Pakistan, from Jun 2014 to Oct 2018. The study was carried out on 105 Sprague Dawley rats for duration of 24 weeks. The animals were randomly distributed in three groups of 35 each. The group I rats were marked as control while rats of group II & III were administered vanadyl sulphate 0.06mg/day and 0.3mg/day respectively. Alanine amino transferase (ALT) and Malondialdehyde (MDA) were measured in serum while comet assay was performed on WBCs. RESULTS: The plasma levels of ALT and MDA were significantly raised in group II and III subjects. Single cell gel electrophoresis (SCGE) / comet assay showed minimal "tail moment" in control group and increased tail moment in group II and III in a dose dependent manner which indicates dsDNA breaks. CONCLUSIONS: It was observed that vanadyl sulphate causes hepatocellular toxicity, oxidative stress and damage to the DNA in usual therapeutic/ supplemental doses. Due to hazardous effects, its use in humans as alternate medicine may be reviewed.

Vanadium compounds and cellular death mechanisms in the A549 cell line: The relevance of the compound valence.

Non-small lung cell carcinoma has a high morbidity and mortality rates. The elective treatment for stage III and IV is cisplatinum that conveys serious toxic side effects. Vanadium compounds are metal molecules with proven antitumor activity that depends on its valence. Therefore, a better understanding of the mechanism of action of vanadium compounds is required. The aim of our study was to investigate the mechanisms of cell death induced by sodium metavanadate (NaVO3 [V(+5)]) and vanadyl sulfate (VOSO4 [(+4)]), both of which have reported apoptotic-inducing activity. We exposed the A549 cell line to various concentrations (0-100 µM) and to different exposure times to each compound and determined the cell viability and expression of caspases, reactive oxygen species (ROS) production, Bcl2, Bax, FasL and NO. Our results showed that neither compounds modified the basal expression of caspases or pro- and anti-apoptotic proteins. The only change observed was the 12- and 14-fold significant increase in ROS production induced by NaVO3 and VOSO4 , respectively, at 100 µm concentrations after 48 hours. Our results suggest that classical apoptotic mechanisms are not related to the cell death induced by the vanadium compounds evaluated here, and showed that the higher ROS production was induced by the [(+4)] valence compound. It is possible that the difference will be secondary to its higher oxidative status and thus higher ROS production, which leads to higher cell damage. In conclusion, our results suggest that the efficacy of the cell death mechanisms induced by vanadium compounds differ depending on the valence of the compound.

Trends in vanadium neurotoxicity.

Vanadium, atomic number 23, is a transition metal widely distributed in nature. It is a major contaminant of fossil fuels and is widely used in industry as catalysts, in welding, and making steel alloys. Over the years, vanadium compounds have been generating interests due to their use as therapeutic agents in the control of diabetes, tuberculosis, and some neoplasms. However, the toxicity of vanadium compounds is well documented in literature with occupational exposure of workers in vanadium allied industries, environmental pollution from combustion of fossil fuels and industrial exhausts receiving concerns as major sources of toxicity and a likely predisposing factor in the aetiopathogenesis of neurodegenerative diseases. A lot has been done to understand the neurotoxic effects of vanadium, its mechanisms of action and possible antidotes. Sequel to our review of the subject in 2011, this present review is to detail the recent insights gained in vanadium neurotoxicity.

Respirable Uranyl-Vanadate-Containing Particulate Matter Derived From a Legacy Uranium Mine Site Exhibits Potentiated Cardiopulmonary Toxicity.

Exposure to windblown particulate matter (PM) arising from legacy uranium (U) mine sites in the Navajo Nation may pose a human health hazard due to their potentially high metal content, including U and vanadium (V). To assess the toxic impact of PM derived from Claim 28 (a priority U mine) compared with background PM, and consider the putative role of metal species U and V. Two representative sediment samples from Navajo Nation sites (Background PM and Claim 28 PM) were obtained, characterized in terms of chemistry and morphology, and fractioned to the respirable (≤ 10 µm) fraction. Mice were dosed with either PM sample, uranyl acetate, or vanadyl sulfate via aspiration (100 µg), with assessments of pulmonary and vascular toxicity 24 h later. Particulate matter samples were also examined for in vitro effects on cytotoxicity, oxidative stress, phagocytosis, and inflammasome induction. Claim 28 PM10 was highly enriched with U and V and exhibited a unique nanoparticle ultrastructure compared with background PM10. Claim 28 PM10 exhibited enhanced pulmonary and vascular toxicity relative to background PM10. Both U and V exhibited complementary pulmonary inflammatory potential, with U driving a classical inflammatory cytokine profile (elevated interleukin [IL]-1ß, tumor necrosis factor-α, and keratinocyte chemoattractant/human growth-regulated oncogene) while V preferentially induced a different cytokine pattern (elevated IL-5, IL-6, and IL-10). Claim 28 PM10 was more potent than background PM10 in terms of in vitro cytotoxicity, impairment of phagocytosis, and oxidative stress responses. Resuspended PM10 derived from U mine waste exhibit greater cardiopulmonary toxicity than background dusts. Rigorous exposure assessment is needed to gauge the regional health risks imparted by these unremediated sites.

Vanadium pentoxide induces the secretion of CXCL9 and CXCL10 chemokines in thyroid cells.

Vanadium is a grey metal, existing in different states of oxidation, whose most common form in commercial products is vanadium pentoxide (V2O5). All vanadium compounds have been considered toxic. A carcinogenic role of vanadium on the thyroid has recently been proposed. However no in vivo or in vitro studies have evaluated thyroid disruption in humans and/or animals after exposure to vanadium. In the present study we evaluate the effect of V2O5 on proliferation, and chemokine secretion in normal thyrocytes. Our study demonstrated that V2O5 has no effect on thyroid follicular cell viability or proliferation, but it is able to induce the secretion of T-helper (Th)1 chemokines into the thyroid, synergistically increasing the effect of important Th1 cytokines such as interferon (IFN)γ and tumor necrosis factor (TNF)α. Through this process, V2O5 promotes the induction and perpetuation of an inflammatory reaction in the thyroid. Further studies are necessary to evaluate thyroid function, and nodules, in subjects occupationally exposed, or living in polluted areas.