RESUMO
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.
Assuntos
Neoplasias Pulmonares/induzido quimicamente , Compostos de Vanádio/efeitos adversos , Compostos de Vanádio/toxicidade , Animais , Relação Dose-Resposta a Droga , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Exposição por Inalação , Pulmão/efeitos dos fármacos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Medição de Risco , Testes de Toxicidade Crônica , Compostos de Vanádio/administração & dosagemRESUMO
This study examined the effects of vanadyl sulfate (VOSO4) on the livers of nondiabetic and streptozotocin-induced diabetic rats. Rats were divided into 6 groups. Groups 1, 2, and 3 consisted of nondiabetic rats that were, respectively, control animals or those receiving an intraperitoneal (i.p.) injection of either 5 or 10 mg·kg-1 (i.p.) VOSO4 for 30 days. Groups 4, 5, and 6 consisted of diabetic animals that were, respectively, control animals or those treated with 5 or 10 mg·kg-1 (i.p.) VOSO4 for 30 days. Results showed that VOSO4 reduced body mass in nondiabetic rats, whereas it increased body mass in diabetic groups. Plasma transaminases (aspartate aminotransferase, alanine aminotransferase), lactate dehydrogenase, and alkaline phosphatase activities and malondialdehyde levels were increased, while liver catalase and superoxide dismutase activities were profoundly decreased in diabetic animals in comparison with enzyme activities in the nondiabetic group. Rats in the diabetic group also showed notable oxidative damage to the liver. Treatment of diabetic rats with VOSO4 decreased the hepatotoxic markers, significantly restored the activities of antioxidant enzymes, and attenuated histopathological changes in liver tissue. In nondiabetic rats, VOSO4 treatment increased most of the hepatotoxic markers, reduced antioxidant enzyme activities, and induced pronounced oxidative damage in liver tissue. These data suggest that treatment with VOSO4 exerts toxic effects in healthy animals and significantly prevents liver oxidative damage in streptozotocin-induced diabetic rats, but without total safety. Further studies are needed to clarify its mechanism of action.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Fígado/efeitos dos fármacos , Compostos de Vanádio/efeitos adversos , Animais , Glicemia , Peso Corporal/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Diabetes Mellitus Experimental/induzido quimicamente , Humanos , Fígado/patologia , Testes de Função Hepática , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Estreptozocina/toxicidade , Resultado do TratamentoRESUMO
Vanadium is a transition metal which creates a number of inorganic and organic derivatives with various organic substances. Some of these compounds have pharmaceutical significance, e.g. vanadyl cation, vanadate and bis(maltolato) oxovanadium(IV). Vanadium compounds are competence inhibitors of protein tyrosine phosphatases (PTP). They have anti-tumor properties, capable of inhibiting cell proliferation at the concentrations of several micromoles. They also display insulin-mimetic and hypoglycemic properties. As they can increase the activity of the insulin-like growth factor I receptor, they stimulate glycogen synthesis, increase the number of GLUT-4 transporters in the cell membrane and impair gluconeogenesis. In addition to their effects on sugar metabolism, vanadium compounds increase the synthesis of fatty acids, reducing the concentration of glucose in the blood. Thanks to their mitotic properties, low concentrations of vanadium compounds are also able to induce ß cell regeneration. Clinical tests have shown that vanadium compounds may be used as antidiabetic drugs with low toxicity. However, the range of therapeutic concentrations is very narrow; at concentrations as low a several micromoles vanadium compounds inhibit cell proliferation and cause apoptosis, necrosis and inflammation.
Assuntos
Hipoglicemiantes/farmacologia , Compostos de Vanádio/farmacologia , Animais , Gluconeogênese/efeitos dos fármacos , Humanos , Insulina/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Compostos de Vanádio/efeitos adversos , Compostos de Vanádio/toxicidadeRESUMO
The US Environmental Protection Agency (USEPA) is currently conducting a toxicological review of vanadium pentoxide (V2O5). As part of that effort, the Agency will need to address the fact that while a National Toxicology Program (NTP) chronic inhalation bioassay of V2O5 produced clear evidence of treatment-related lung tumors in both male and female B6C3F1 mice, neither of these responses were dose-related across the groups exposed to 1, 2, and 4mg/m(3). While lung tumor incidence was significantly elevated in all three exposed groups relative to that in the control groups, it was essentially flat across them. Herein we report results from computing poly-3-adjusted Cochran-Armitage trend test statistics with and without inclusion of the lung tumor incidence data from control group mice. These results confirm the absence of any significant dose-related effect on mouse lung tumor incidence in the study groups exposed to V2O5. We also considered two estimates of area under the vanadium lung burden versus time curve as plausible alternative dose metrics to the V2O5 chamber concentration. However, these alternative dose metrics were so highly correlated with the V2O5 chamber concentration (r=0.998) that nothing is to be gained from their use in place of the V2O5 chamber concentration in attempts to perform dose-response modeling of the tumor incidence or unit cancer risk computations. At the present time, there is no scientific basis to support linear (or nonlinear) extrapolations of estimated cancer risks to V2O5 exposure levels below 1mg/m(3). Additional tumor data at multiple V2O5 concentrations lower than 1mg/m(3) are required to support such extrapolations.
Assuntos
Carcinogênese/induzido quimicamente , Carcinógenos/toxicidade , Exposição por Inalação/efeitos adversos , Compostos de Vanádio/efeitos adversos , Animais , Bioensaio/métodos , Feminino , Incidência , Pulmão/efeitos dos fármacos , Neoplasias Pulmonares/induzido quimicamente , Masculino , Camundongos , Ratos , Medição de Risco , Estados UnidosRESUMO
The number of studies on microcrystals containing silver has increased in recent decades. Among the silver-containing microcrystals, α-AgVO3 has gained prominence owing to its polymorphism that allows it to exert interesting antimicrobial activity against pathogenic microorganisms. The aim of this study was to evaluate the antifungal activity and cytotoxicity of three different α-AgVO3 microcrystals when in solution. α-AgVO3 microcrystals were synthesized using the co-precipitation method at three different temperatures (10⯰C, 20⯰C, and 30⯰C), and then characterized by X-ray diffraction and scanning electron microscopy. The antifungal activity of α-AgVO3 microcrystals against Candida albicans was determined by estimating the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). Fluorescence images were obtained to confirm antifungal concentrations. To assess the biocompatibility of microcrystals applied at MIC and MFC on keratinocytes cells (NOK-si), an Alamar Blue assay, scanning electron microscopy, and a DNA gel integrity test were carried out. The quantitative and qualitative results showed that, regardless of the co-precipitation method used to synthetize α-AgVO3 microcrystals, C. albicans growth was visibly inhibited at 3.9⯵g/mL (MIC) and completely inhibited at 15.62⯵g/mL (MFC). The cytotoxic and genotoxic outcomes revealed that the MIC and MFC concentrations did not affect NOK-si cell morphology, proliferation, or DNA integrity. The search for new antimicrobial materials has been the focus of the research community recently because of increases in microbial resistance. The findings reported herein demonstrate a novel antifungal and non-cytotoxic material that could be used in biomedical and dental applications.
Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Óxidos/farmacologia , Compostos de Prata/farmacologia , Compostos de Vanádio/farmacologia , Antifúngicos/efeitos adversos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Testes de Sensibilidade Microbiana , Microscopia de Fluorescência , Óxidos/efeitos adversos , Compostos de Prata/efeitos adversos , Compostos de Vanádio/efeitos adversosRESUMO
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.
Assuntos
Síndromes Neurotóxicas/etiologia , Vanádio/efeitos adversos , Vanádio/toxicidade , Animais , Encéfalo/metabolismo , Encéfalo/fisiologia , Humanos , Síndromes Neurotóxicas/fisiopatologia , Compostos de Vanádio/efeitos adversos , Compostos de Vanádio/toxicidadeRESUMO
Recently it has been hypothesized that vanadium serves a carcinogenic role in the thyroid. However, to date, no in vivo or in vitro studies have evaluated thyroid disruption in humans and/or animals following exposure to vanadium. The present study evaluated the effect of vanadium pentoxide (V2O5) on cell viability and proliferation, and chemokine (CXC motif) ligand (CXCL)8 and CXCL11 secretion in normal thyrocytes. The results demonstrated that V2O5 had no effect on thyroid follicular cell viability and proliferation. However, V2O5 was able to induce the secretion of CXCL8 and CXCL11 chemokines from thyrocytes. Notably, V2O5 synergistically increased the effect of the interferon (IFN)γ on CXCL11 secretion. In addition, V2O5 synergistically increased the effect of tumor necrosis factorα on CXCL8 secretion, and abolished the inhibitory effect of IFNγ. Overall this induction of CXCL8 and CXCL11 secretion may lead to the induction and perpetuation of an inflammatory reaction in the thyroid. Further studies are now required to evaluate thyroid function and nodule development in subjects who are occupationally exposed, or living in polluted areas.
Assuntos
Quimiocina CXCL11/imunologia , Inflamação/induzido quimicamente , Interleucina-8/imunologia , Glândula Tireoide/efeitos dos fármacos , Compostos de Vanádio/efeitos adversos , Adulto , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Humanos , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Glândula Tireoide/citologia , Glândula Tireoide/imunologia , Adulto JovemRESUMO
Vanadium is a soft, silverygrey metal with a number of different oxidation states. The most common commercial form of vanadium is vanadium pentoxide (V2O5). All vanadium compounds are considered toxic. An increase in skin rashes has been observed in certain vanadium workers, including the development of atopic dermatitis. However, to the best of our knowledge, no prior in vivo or in vitro studies have evaluated the effect of vanadium exposure in human dermal fibroblasts. The present study evaluated the effect of V2O5 on proliferation and chemokine secretion in dermal fibroblasts. The results revealed that V2O5 had no significant effect on the viability or proliferation of fibroblasts, however it was able to induce the secretion of Thelper (Th)1 chemokines from dermal fibroblasts, synergistically increasing the effect of important Th1 cytokines, including interferonγ and tumor necrosis factorα. Through these processes, V2O5 may lead to the induction and perpetuation of an inflammatory reaction in dermal tissue. The induction and perpetuation of inflammation in the dermis and the variety of involved candidate genes may be at the base of V2O5induced effects following occupational and environmental exposures. Further studies are necessary to evaluate dermal integrity and manifestations in subjects who are occupationally exposed, or living in polluted areas.
Assuntos
Quimiocina CXCL10/imunologia , Quimiocina CXCL9/imunologia , Fibroblastos/efeitos dos fármacos , Compostos de Vanádio/imunologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CXCL10/análise , Quimiocina CXCL9/análise , Fibroblastos/citologia , Fibroblastos/imunologia , Humanos , Pele/citologia , Pele/efeitos dos fármacos , Pele/imunologia , Compostos de Vanádio/efeitos adversosRESUMO
Vanadium compounds have been known to have beneficial therapeutic properties since the turn of the century, but it was not until 1965 when it was discovered that those effects could be extended to treating cancer. Some vanadium compounds can combat common markers of cancer, which include metabolic processes that are important to initiating and developing the phenotypes of cancer. It is appropriate to consider vanadium as a treatment option due to the similarities in some of the metabolic pathways utilized by both diabetes and cancer and therefore is among the few drugs that are effective against more than one disease. The development of vanadium compounds as protein phosphatase inhibitors for the treatment of diabetes may be useful for potential applications as an anticancer agent. Furthermore, the ability of vanadium to redox cycle is also important for biological properties and is involved in the pathways of reactive oxygen species. Early agents including vanadocene and peroxovanadium compounds have been investigated in detail, and the results can be used to gain a better understanding of how some vanadium compounds are modifying the metabolic pathways potentially developing cancer. Considering the importance of coordination chemistry to biological responses, it is likely that proper consideration of compound formulation will improve the efficacy of the drug. Future development of vanadium-based drugs should include consideration of drug formulation at earlier stages of drug development.
Assuntos
Anticarcinógenos/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Compostos de Vanádio/uso terapêutico , Animais , Anticarcinógenos/efeitos adversos , Anticarcinógenos/química , Anticarcinógenos/metabolismo , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Antineoplásicos/metabolismo , Complexos de Coordenação , Suplementos Nutricionais/efeitos adversos , Composição de Medicamentos , Descoberta de Drogas/métodos , Humanos , Estrutura Molecular , Neoplasias/metabolismo , Neoplasias/patologia , Relação Estrutura-Atividade , Compostos de Vanádio/efeitos adversos , Compostos de Vanádio/química , Compostos de Vanádio/metabolismoRESUMO
Vanadium (V) is a transition metal often adhered to particulate matter and released into the atmosphere as vanadium pentoxide (V2O5) by the burning of fossil fuels. This air pollutant causes adverse effects in the immune system. Lymphocytosis and splenomegaly have been reported with increased white pulp in mice after V inhalation. The effect of V on the immune system as related to sex has been poorly investigated. This study sought to determine if V inhalation (a) produced lymphoproliferation that could explain the changes previously observed in the spleen and in peripheral blood lymphocyte counts and (b) whether any observed effects differed due to gender. Immunohistochemical analyses of Ki-67, a specific proliferation marker, was made in the spleens of CD-1 male and female mice exposed for 1 h, twice a week, over a 12-week period to V2O5 (at 1.4 mg V2O5/m(3)) by whole-body inhalation; similar analyses were performed on spleens of control mice exposed to vehicle (filtered air). The results showed that in male mice there was a significant increase in percentage of Ki-67 immunopositive lymphocytes starting from the second week and until the end of the exposure. The Ki-67 signal was cytoplasmic and nuclear in the exposed males, while in controls the signal was only nuclear. In female mice, V inhalation singificantly increased the percentage of proliferating lymphocytes only after 1 week of exposure. Ki-67 signal was observed only in the nucleus of lymphocytes from the control and exposed females. The results here help to explain the splenomegaly and lymphocytosis observed previously in male mice and support the lymphoproliferative effect induced by V. Lastly, the finding that there was a sex difference in the effect of vanadium on lymphocyte proliferation suggests a role for sex hormones in potential protection against V immunotoxicity; however, further studies are needed to support this hypothesis.
Assuntos
Linfócitos/imunologia , Transtornos Linfoproliferativos/imunologia , Sexo , Compostos de Vanádio/imunologia , Vanádio/imunologia , Poluição do Ar/efeitos adversos , Animais , Proliferação de Células , Células Cultivadas , Feminino , Combustíveis Fósseis/efeitos adversos , Humanos , Inalação , Transtornos Linfoproliferativos/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos , Material Particulado/efeitos adversos , Material Particulado/toxicidade , Baço/patologia , Vanádio/efeitos adversos , Compostos de Vanádio/efeitos adversosRESUMO
Small increases in concentrations of ambient particulate matter (PM*) have been linked to adverse health effects, especially in older people and people with preexisting respiratory disease. Some epidemiologic studies have shown the association to be stronger with PM less than 2.5 microm in aerodynamic diameter (PM2.5) than with PM less than 10 microm in aerodynamic diameter (PM10). Some scientists and regulators suggest that 2.5 microm might be an arbitrary cutoff and that the effects might be more pronounced for PM less than 0.1 microm in aerodynamic diameter (ultrafine PM). Our first aim was to determine the relation between size of respirable particles and particle toxicity, as well as the health effects of short-term increases (spikes) in particle concentration against backgrounds of relatively low or high baseline exposures. Our second aim was to determine the effect of spikes in concentration of fine particles (0.7 microm in mass median aerodynamic diameter [MMAD]) and ultrafine particles (35 nm in count median diameter [CMD]) of disparate composition: vanadium pentoxide (V2O5) and carbon black. The relative toxicity of these particles was determined in aged rats with mild pulmonary inflammation induced by instilled endotoxin. Our third aim was to determine the influence of age (aged vs young adult) on particle-induced toxicity in these rats.
Assuntos
Carbono/efeitos adversos , Exposição por Inalação/análise , Compostos de Vanádio/efeitos adversos , Fatores Etários , Animais , Carbono/administração & dosagem , Masculino , New Mexico , Tamanho da Partícula , Pneumonia/fisiopatologia , Ratos , Ratos Endogâmicos F344 , Ratos Sprague-Dawley , Compostos de Vanádio/administração & dosagemRESUMO
The safety and efficacy of vanadyl sulfate (VS) was tested in a single-blind, placebo-controlled study. Eight patients (four men and four women) with non-insulin-dependent diabetes mellitus (NIDDM) received VS (50 mg twice daily orally) for 4 weeks. Six of these patients (four men and two women) continued in the study and were given a placebo for an additional 4 weeks. Euglycemic-hyperinsulinemic clamps were performed before and after the VS and placebo phases. VS was associated with gastrointestinal side effects in six of eight patients during the first week, but was well tolerated after that. VS administration was associated with a 20% decrease in fasting glucose concentration (from 9.3 +/- 1.8 to 7.4 +/- 1.4 mmol/L, P < .05) and a decrease in hepatic glucose output (HGO) during hyperinsulinemia (from 5.0 +/- 1.0 pre-VS to 3.1 +/- 0.9 micromol/kg x min post-VS, P < .02). The improvement in fasting plasma glucose and HGO that occurred during VS treatment was maintained during the placebo phase. VS had no significant effects on rates of total-body glucose uptake, glycogen synthesis, glycolysis, carbohydrate (CHO) oxidation, or lipolysis during euglycemic-hyperinsulinemic clamps. We conclude that VS at the dose used was well tolerated and resulted in modest reductions of fasting plasma glucose and hepatic insulin resistance. However, the safety of larger doses and use of vanadium salts for longer periods remains uncertain.
Assuntos
Carboidratos/sangue , Diabetes Mellitus Tipo 2/sangue , Hipoglicemiantes/uso terapêutico , Lipídeos/sangue , Compostos de Vanádio/uso terapêutico , Glicemia/análise , Feminino , Técnica Clamp de Glucose , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/sangue , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Placebos , Compostos de Vanádio/efeitos adversosRESUMO
The biotoxic effects of vanadium are variable depending upon a number of factors including the oxidation state of the test compound. This study reports the effects of three vanadium compounds on peripheral erythrocytes. On day 0 female ICR mice received a single injection of vanadium chloride (V-III), vanadyl sulfate (V-IV), or sodium orthovandate (V-V). At scheduled intervals post-injection, the number of circulating erythrocytes [red blood cells per millimeter cubed (RBC/mm3)], reticulocyte percentages, and radioiron uptake percentages were determined and compared to mice receiving saline only. Data show that all three test substances promoted a significant lowering of RBC/mm3 beginning on day 1 for V-IV and V-V and on day 2 for V-III through day 4. The reticulocyte percentages increase followed the same time course as that of the peripheral RBC decrease. Peak reticulocytosis was noted on days 2 and 4 for all three vanadium-treated groups; for V-IV and V-V the increase continued to day 6. Radioiron data showed an erythropoietic stimulation by a significant increase in uptake percentages on days 4-6 after vanadium injections compared to saline-treated controls.
Assuntos
Eritrócitos/fisiologia , Eritropoese/efeitos dos fármacos , Compostos de Vanádio/efeitos adversos , Animais , Eritrócitos/efeitos dos fármacos , Feminino , Radioisótopos de Ferro , Camundongos , Camundongos Endogâmicos , Oxirredução , Reticulócitos/efeitos dos fármacos , Reticulócitos/fisiologiaRESUMO
The authors describe the influence of vanadyl sulphate on liver Golgi complexes in control and streptozotocin (STZ)-diabetic rats. VOSO4, one of inorganic vanadium compounds widely used in animal models and human diabetes, acts as an insulin-mimetic drug and is relatively well known as a complex activated or inhibited on many enzymes involved in carbohydrate or lipid metabolic pathways. A relatively small in scope investigation was performed on subcellular levels, while changes of Golgi complexes under vanadium influence have not been described with the exception of our previous investigations with four organic derivatives. This paper presents the action of vanadyl sulphate used in 3mM in 0.5% NaCl as a drinking solution for 7 days on control and STZ-diabetic rat liver Golgi complexes. Changes induced by this vanadium compound were greater in the controls as compared to the diabetic rats, what was true for both biochemical and morphological data. Physiological and biochemical analyses showed a partial normalization of the investigated parameters in diabetic animals after short time treatment with vanadyl ions, although STZ-diabetic, vanadium treated rats were affected by two types of adverse effects exterted by these compounds. The controls manifested more numerous and advanced subcellular changes. The moderately developed Golgi apparatus showed no major changes. In the control group, subcellular changes were seen sporadically. More extended Golgi complexes showed certain anomalies.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Complexo de Golgi/efeitos dos fármacos , Fígado/efeitos dos fármacos , Compostos de Vanádio/farmacologia , Animais , Diabetes Mellitus Experimental/fisiopatologia , Feminino , Complexo de Golgi/metabolismo , Complexo de Golgi/ultraestrutura , Fígado/metabolismo , Fígado/ultraestrutura , Microscopia Eletrônica , Ratos , Ratos Wistar , Compostos de Vanádio/efeitos adversosRESUMO
Vanadium is the 21st most abundant element in the Earth's crust and the 2nd-to-most abundant transition metal in sea water. The element is ubiquitous also in freshwater and nutrients. The average body load of a human individual amounts to 1 mg. The omnipresence of vanadium hampers checks directed towards its essentiality. However, since vanadate can be considered a close blueprint of phosphate with respect to its built-up, vanadate likely takes over a regulatory function in metabolic processes depending on phosphate. At common concentrations, vanadium is non-toxic. The main source for potentially toxic effects caused by vanadium is exposure to high loads of vanadium oxides in the breathing air of vanadium processing industrial enterprises. Vanadium can enter the body via the lungs or, more commonly, the stomach. Most of the dietary vanadium is excreted. The amount of vanadium resorbed in the gastrointestinal tract is a function of its oxidation state (V(V) or V(IV)) and the coordination environment. Vanadium compounds that enter the blood stream are subjected to speciation. The predominant vanadium species in blood are vanadate and vanadyl bound to transferrin. From the blood stream, vanadium becomes distributed to the body tissues and bones. Bones act as storage pool for vanadate. The aqueous chemistry of vanadium(V) at concentration <10 µM is dominated by vanadate. At higher concentrations, oligovanadates come in, decavanadate in particular, which is thermodynamically stable in the pH range 2.3-6.3, and can further be stabilized at higher pH by interaction with proteins.The similarity between vanadate and phosphate accounts for the interplay between vanadate and phosphate-dependent enzymes: phosphatases can be inhibited, kinases activated. As far as medicinal applications of vanadium compounds are concerned, vanadium's mode of action appears to be related to the phosphate-vanadate antagonism, to the direct interaction of vanadium compounds or fragments thereof with DNA, and to vanadium's contribution to a balanced tissue level of reactive oxygen species. So far vanadium compounds have not yet found approval for medicinal applications. The antidiabetic (insulin-enhancing) effect, however, of a singular vanadium complex, bis(ethylmaltolato)oxidovanadium(IV) (BEOV), has revealed encouraging results in phase IIa clinical tests. In addition, in vitro studies with cell cultures and parasites, as well as in vivo studies with animals, have revealed a broad potential spectrum for the application of vanadium coordination compounds in the treatment of cardiac and neuronal disorders, malignant tumors, viral and bacterial infections (such as influenza, HIV, and tuberculosis), and tropical diseases caused by parasites, e.g., Chagas' disease, leishmaniasis, and amoebiasis.
Assuntos
Compostos de Vanádio , Vanádio/metabolismo , Fragmentação do DNA , Humanos , Compostos de Vanádio/efeitos adversos , Compostos de Vanádio/metabolismo , Compostos de Vanádio/uso terapêuticoRESUMO
BACKGROUND: Vanadium compounds are able to reduce blood glucose in experimentally- induced diabetic rats and type 2 diabetic patients, but data about their long- term safety and efficacy in diabetic patients are scarce. METHODS: Fourteen type 1 diabetic patients received oral vanadyl sulfate (50 - 100 mg TID) for a period of 30 months. Fasting blood sugar (FBS), lipid levels, hematologic, and biochemical parameters were measured before and periodically during the treatment. RESULTS: The daily doses of insulin decreased from 37.2 ± 5.5 to 25.8 ± 17.3 units/day and at the same time the mean FBS decreased from 238 ± 71 to 152 ± 42 mg/dL. Meanwhile, there was a decrease in plasma total cholesterol without any change in triglyceride level. No significant clinical or paraclinical side effects, with the exception for mild diarrhea at the beginning of treatment, were observed during 30 months therapy. CONCLUSION: Vanadium is effective and safe for long- term use in type 1 diabetic patients.
Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Compostos de Vanádio/uso terapêutico , Adolescente , Adulto , Criança , Diabetes Mellitus Tipo 1/sangue , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/uso terapêutico , Masculino , Compostos de Vanádio/efeitos adversos , Adulto JovemRESUMO
Treatment with inorganic and organic compounds of vanadium has been shown to exert a wide range of cardioprotective effects in myocardial ischemia/reperfusion-induced injury, myocardial hypertrophy, hypertension, and vascular diseases. Furthermore, administration of vanadium compounds improves cardiac performance and smooth muscle cell contractility and modulates blood pressure in various models of hypertension. Like other vanadium compounds, we documented bis(1-oxy-2-pyridinethiolato) oxovanadium (IV) [VO(OPT)] as a potent cardioprotective agent to elicit cardiac functional recovery in myocardial infarction and pressure overload-induced hypertrophy. Vanadium compounds activate Akt signaling through inhibition of protein tyrosine phosphatases, thereby eliciting cardioprotection in myocardial ischemia/reperfusion-induced injury and myocardial hypertrophy. Vanadium compounds also promote cardiac functional recovery by stimulation of glucose transport in diabetic heart. We here discuss the current understanding of mechanisms underlying vanadium compound-induced cardioprotection and propose a novel therapeutic strategy targeting for Akt signaling to rescue cardiomyocytes from heart failure.
Assuntos
Cardiotônicos/uso terapêutico , Cardiopatias/prevenção & controle , Proteína Oncogênica v-akt/fisiologia , Compostos de Vanádio/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Cardiomegalia/patologia , Cardiomegalia/prevenção & controle , Cardiotônicos/efeitos adversos , Angiopatias Diabéticas/patologia , Angiopatias Diabéticas/prevenção & controle , Cardiopatias/patologia , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Compostos de Vanádio/efeitos adversosRESUMO
AIMS: To investigate a worker who experienced systemic and respiratory symptoms when exposed to a vanadium containing powder used as a catalyst in the production of maleic anhydride. METHODS: The investigation included inhalation challenge with the suspected compound combined with monitoring of lung function tests and post-challenge bronchoalveolar lavage. RESULTS: Exposure to the vanadium containing catalyst for 120 minutes resulted in a sustained decline in forced vital capacity and forced expiratory volume in one second, while the transfer factor for carbon monoxide did not change significantly. The subject developed fever and peripheral blood neutrophilia. Bronchoalveolar lavage performed 48 hours after the end of challenge exposure showed a marked increase in neutrophils (60% of total cell count). CONCLUSIONS: Exposure to vanadium can cause a metal fume fever-like syndrome associated with neutrophilic alveolitis.
Assuntos
Alveolite Alérgica Extrínseca/induzido quimicamente , Febre/induzido quimicamente , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Compostos de Vanádio/efeitos adversos , Adulto , Albuterol/uso terapêutico , Alveolite Alérgica Extrínseca/tratamento farmacológico , Broncodilatadores/uso terapêutico , Poeira , Fluxo Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Doenças Profissionais/tratamento farmacológico , Capacidade Vital/efeitos dos fármacosRESUMO
We prospectively investigated the lower airway response in boilermakers overhauling an oil-powered boiler. We studied 26 male boilermakers with a mean age (SD) of 43.3 (8.6) yr. Pre-exposure spirometry and methacholine challenge tests were performed before beginning the boiler overhaul; postexposure tests were performed after approximately 4 wk of work on the boiler. Exposure to particulates with an aerodynamic diameter of 10 microns and smaller (PM10) and respirable vanadium dust were estimated using daily work diaries and a personal sampling device for respirable particles. Using these estimates, we calculated average and peak exposure between pre- and postexposure tests for each subject. The average PM10 concentration ranged from 1.44 to 6.69 mg/m3, with a mean (SD) of 3.22 (1.42) mg/m3; the average vanadium concentration ranged from 2.2 to 31.3, with a mean (SD) of 12.2 (9.1) micrograms/m3. The mean postexposure fall in FEV1 was 140 +/- 160 ml (p < 0.01); 24 of 26 subjects had a drop in FEV1. For each subject, the adjusted change in FEV1 (delta FEV1.adj) was calculated by dividing the change in FEV1 by the average of the pre- and postexposure FEV1 values. The delta FEV1.adj was regressed, controlling age and current smoking status, on average and peak exposure to both PM10 and vanadium. There was a dose-response relationship between average and peak PM10 exposure and delta FEV1.adj: beta = -0.91% per mg/m3, p = 0.08 and beta = -1.03% per mg/m3, p = 0.03, respectively. However, there was no relationship between delta FEV1.adj and respirable vanadium dust concentration. Furthermore, there was no postexposure change in nonspecific airway responsiveness. In summary, we found a significant fall in FEV1 and a dose-response relationship between delta FEV1.adj and average and peak PM10 exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Obstrução das Vias Respiratórias/induzido quimicamente , Óleos Combustíveis/efeitos adversos , Doenças Profissionais/induzido quimicamente , Adulto , Poluentes Ocupacionais do Ar/efeitos adversos , Poluentes Ocupacionais do Ar/análise , Obstrução das Vias Respiratórias/diagnóstico , Testes de Provocação Brônquica/estatística & dados numéricos , Engenharia/estatística & dados numéricos , Humanos , Modelos Lineares , Masculino , Cloreto de Metacolina , Pessoa de Meia-Idade , Doenças Profissionais/diagnóstico , Estudos Prospectivos , Espirometria/estatística & dados numéricos , Estatísticas não Paramétricas , Inquéritos e Questionários , Compostos de Vanádio/efeitos adversos , Compostos de Vanádio/análiseRESUMO
OBJECTIVES: Among other constituents, fuel oil ash contains vanadium pentoxide, a known respiratory irritant. Exposure to ambient vanadium pentoxide dust has been shown to produce irritation of the eyes, nose, and throat. The usefulness of nasal lavage in detecting an inflammatory response to exposure to fuel oil ash among 37 boilermakers and utility workers was investigated. METHODS: A baseline lavage was performed on the morning of the first day back to work after an average of 114 days away from work (range 36 hours to 1737 days). A lavage was performed after exposure on the morning three days after the baseline lavage. Exposure to respirable particulate matter of diameter < or = 10 microns (PM10) and respirable vanadium dust were estimated with daily work diaries and a personal sampling device for respirable particulates. These estimates were made for each subject on each workday during the three days between lavages. For each subject, the adjusted change in polymorphonuclear cells was calculated by dividing the change in polymorphonuclear cell counts by the average of the counts before and after exposure. The association between the adjusted polymorphonuclear cell counts and exposure was assessed with multiple linear regression, adjusted for age and current smoking. RESULTS: Personal sampling (one to 10 hour time weighted average) showed a range of PM10 concentrations of 50 to 4510 micrograms/m3, and respirable vanadium dust concentration of 0.10 to 139 micrograms/m3. In smokers the adjusted polymorphonuclear cell count was not significantly different from zero (-0.1%, P > 0.5), but in nonsmokers it was significantly greater than zero (+50%, P < 0.05). In both non-smokers and smokers, there was considerable variability in adjusted polymorphonuclear cell counts and a dose-response relation between these adjusted cell counts and either PM10 or respirable vanadium dust exposure could not be found. CONCLUSION: A significant increase in polymorphonuclear cells in non-smokers but not smokers was found. This suggests that in non-smokers, exposure to fuel oil ash is associated with upper airway inflammation manifested as increased polymorphonuclear cell counts. The lack of an increase in polymorphonuclear cells in smokers may reflect either a diminished inflammatory response or may indicate that smoking masks the effect of exposure to fuel oil ash.