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1.
Toxicol Appl Pharmacol ; 412: 115395, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33421504

RESUMO

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.


Assuntos
Vanadatos/farmacocinética , Compostos de Vanádio/farmacocinética , Administração Oral , Animais , Carga Corporal (Radioterapia) , Água Potável , Feminino , Suco Gástrico/química , Absorção Gastrointestinal , Secreções Intestinais/química , Fígado/metabolismo , Masculino , Oxirredução , Ratos Sprague-Dawley , Distribuição Tecidual , Toxicocinética , Vanadatos/administração & dosagem , Vanadatos/sangue , Vanadatos/toxicidade , Compostos de Vanádio/administração & dosagem , Compostos de Vanádio/sangue , Compostos de Vanádio/toxicidade
2.
Inorg Chem ; 54(17): 8237-50, 2015 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-26280599

RESUMO

The speciation of the potential antitumor agent vanadocene dichloride ([Cp2VCl2], abbreviated with VDC) in the blood plasma was studied by instrumental (EPR, ESI-MS, MS-MS, and electronic absorption spectroscopy) and computational (DFT) methods. The behavior of VDC at pH 7.4 in aqueous solution, the interaction with the most important bioligands of the plasma (oxalate, carbonate, phosphate, lactate, citrate, histidine, and glycine among those with low molecular mass and transferrin and albumin between the proteins) was evaluated. The results suggest that [Cp2VCl2] transforms at physiological pH to [Cp2V(OH)2] and that only oxalate, carbonate, phosphate, and lactate are able to displace the two OH(-) ions to yield [Cp2V(ox)], [Cp2V(CO3)], [Cp2V(lactH(-1))], and [Cp2V(HPO4)]. The formation of the adducts with oxalate, carbonate, lactate, and hydrogen phosphate was confirmed also by ESI-MS and MS-MS spectra. The stability order is [Cp2V(ox)] ≫ [Cp2V(CO3)] > [Cp2V(lactH(-1))] > [Cp2V(HPO4)]. No interaction between VDC and plasma proteins was detected under our experimental conditions. Several model systems containing the bioligands (bL) in the same relative ratio as in the blood samples were also examined. Finally, the speciation of VDC in the plasma was studied. The results obtained show that the model systems behave as the blood plasma and indicate that when V concentration is low (10 µM) VDC is transported in the bloodstream as [Cp2V(ox)]; when V concentration is high (100 µM) oxalate binds only 9.2 µM of [Cp2V](2+), whereas the remaining part distributes between [Cp2V(CO3)] (main species) and [Cp2V(lactH(-1))] (minor species); and when V concentration is in the range 10-100 µM [Cp2V](2+) distributes between [Cp2V(ox)] and [Cp2V(CO3)].


Assuntos
Antineoplásicos/sangue , Antineoplásicos/química , Compostos de Vanádio/sangue , Compostos de Vanádio/química , Proteínas Sanguíneas/química , Modelos Moleculares , Conformação Molecular , Teoria Quântica
3.
Inorg Chem ; 52(20): 11975-85, 2013 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-24090437

RESUMO

The interaction of VO(2+) ion and four insulin-enhancing compounds, [VO(ma)2], [VO(dhp)2], [VO(acac)2], and cis-[VO(pic)2(H2O)], where Hma, Hdhp, Hacac, and Hpic are maltol, 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone, acetylacetone, and picolinic acid, with holo-transferrin (holo-hTf) was studied through the combined application of electron paramagnetic resonance (EPR) and density functional theory (DFT) methods. Since in holo-hTf all of the specific binding sites of transferrin are saturated by Fe(3+) ions, VO(2+) can interact with surface sites (here named sites C), probably via the coordination of His-N, Asp-COO(-), and Glu-COO(-) donors. In the ternary systems with the insulin-enhancing compounds, mixed species are observed with Hma, Hdhp, and Hpic with the formation of VOL2(holo-hTf), explained through the interaction of cis-[VOL2(H2O)] (L = ma, dhp) or cis-[VOL2(OH)](-) (L = pic) with an accessible His residue that replaces the monodentate H2O or OH(-) ligand. The residues of His-289, His-349, His-473, and His-606 seem the most probable candidates for the complexation of the cis-VOL2 moiety. The lack of a ternary complex with Hacac was attributed to the square-pyramidal structure of [VO(acac)2], which does not possess equatorial sites that can be replaced by the surface His-N. Since holo-transferrin is recognized by the transferrin receptor, the formation of ternary complexes between VO(2+) ion, a ligand L(-), and holo-hTf may be a way to transport vanadium compounds inside the cells.


Assuntos
Insulina/química , Transferrina/química , Compostos de Vanádio/química , Humanos , Insulina/sangue , Estrutura Molecular , Teoria Quântica , Compostos de Vanádio/sangue
4.
Environ Toxicol Pharmacol ; 32(3): 447-56, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22004965

RESUMO

Vanadium pentoxide (V(2)O(5)) inhalation effect on platelet function in mice was explored, as well as the in vitro effect on human platelets. Mouse blood samples were collected and processed for aggregometry and flow cytometry to assess the presence of P-selectin and monocyte-platelet conjugates. Simultaneously, human platelets were processed for aggregometry(.) The mouse results showed platelet aggregation inhibition in platelet-rich-plasma (PRP) at four-week exposure time, and normality returned at eight weeks of exposure, remaining unchanged after the exposure was discontinued after four weeks. This platelet aggregation inhibition effect was reinforced with the in vitro assay. In addition, P-selectin preserved their values during the exposure, until the exposure was discontinued during four weeks, when this activation marker increased. We conclude that vanadium affects platelet function, but further studies are required to evaluate its effect on other components of the hemostatic system.


Assuntos
Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Compostos de Vanádio/toxicidade , Administração por Inalação , Poluentes Atmosféricos/sangue , Poluentes Atmosféricos/toxicidade , Animais , Células Cultivadas , Humanos , Masculino , Camundongos , Camundongos Endogâmicos , Selectina-P/metabolismo , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Plasma Rico em Plaquetas/efeitos dos fármacos , Compostos de Vanádio/administração & dosagem , Compostos de Vanádio/sangue
5.
Med Tr Prom Ekol ; (11): 20-4, 2011.
Artigo em Russo | MEDLINE | ID: mdl-22288183

RESUMO

The authors give examples of mass spectrometric detection of vanadium in workplace air of metallurgic production. Reliable correlation was seen between divanadium pentoxide concentration in workplace air and whole blood vanadium levels in workers and clerks of metallurgic enterprise.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Ligas , Ferro , Manganês/sangue , Metalurgia , Exposição Ocupacional/análise , Compostos de Vanádio/sangue , Ar/análise , Humanos , Espectrometria de Massas
6.
Curr Med Chem ; 17(31): 3701-38, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20846109

RESUMO

Low molecular weight and high molecular weight metal ion binders present in blood plasma are shortly described. The binding of vanadium and ruthenium complexes by these components has received much attention, namely their interactions with human serum albumin and transferrin, and these studies are critically reviewed. The influence of the protein binding on the bioavailability of the prospective drugs, namely on the transport by blood plasma and uptake by cells is also discussed. It is concluded that vanadium compounds are mainly transported in blood by transferrin, but that no study has properly addressed the influence of albumin and transferrin in the vanadium uptake by cells. Ruthenium complexes bind strongly to HSA, most likely at the level of His residues, leading to the formation of stable adducts. If the kinetics of binding to this protein is fast enough, probably they are mainly transported by this serum protein. Nevertheless, at least for a few Ru(III)-complexes, hTf seems to play an active role in the uptake of ruthenium, while HSA may provide selectivity and higher activity for the compounds due to an enhanced permeability effect.


Assuntos
Proteínas Sanguíneas/metabolismo , Complexos de Coordenação/sangue , Compostos de Rutênio/sangue , Compostos de Vanádio/sangue , Transporte Biológico , Ensaios Clínicos como Assunto , Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , Complexos de Coordenação/uso terapêutico , Humanos , Peso Molecular , Ligação Proteica , Rutênio/sangue , Rutênio/química , Rutênio/metabolismo , Compostos de Rutênio/química , Compostos de Rutênio/metabolismo , Compostos de Rutênio/uso terapêutico , Radioisótopos de Rutênio/sangue , Radioisótopos de Rutênio/química , Radioisótopos de Rutênio/metabolismo , Radioisótopos de Rutênio/uso terapêutico , Albumina Sérica/metabolismo , Análise Espectral , Transferrina/metabolismo , Vanádio/sangue , Vanádio/química , Vanádio/metabolismo , Compostos de Vanádio/química , Compostos de Vanádio/metabolismo , Compostos de Vanádio/uso terapêutico
7.
Inorg Chem ; 49(1): 174-87, 2010 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-19947643

RESUMO

The possible biotransformations in the blood serum of four representative insulin-enhancing vanadium compounds, [VO(6-mepic)(2)], cis-[VO(pic)(2)(H(2)O)], [VO(acac)(2)], and [VO(dhp)(2)], where 6-mepic, pic, acac, and dhp indicate the deprotonated forms of 6-methylpicolinic and picolinic acids, acetylacetone, and 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone, were examined. In particular, the behavior of the quinary systems formed by the insulin-enhancing species, human serum apo-transferrin (hTf), human serum albumin (HSA), and lactate (lact) or citrate (citr) at physiological pH and conditions was studied. The results indicate that, besides the case in which the ligand is very weak like 6-mepic, the carrier can interact in some form with VO(2+) ion until its intake into the cell. In fact with stronger ligands like pic, acac, and dhp, VO(2+) is transported not only by transferrin but also as [VO(carrier)(2)] and as mixed species VO(2+)-hTF-carrier. There are two ways in which the undissociated form of a bis-chelated complex can interact with transferrin, one "specific" when the carrier possesses a carboxylate group and behaves like a synergistic anion, and another "non-specific" when an imidazole nitrogen of a histidine residue from hTf replaces an equatorially coordinated water molecule giving rise to a ternary species with cis-octahedral geometry and cis-VO(carrier)(2)(hTf) stoichiometry. It is found that also albumin can participate in the transport of an insulin-enhancing compound forming a mixed species cis-VO(carrier)(2)(HSA), when the carrier stabilizes in aqueous solution the cis-octahedral form, or the dinuclear compound (VO)(2)(d)HSA, when the carrier forms unstable complexes. These insights were confirmed through density functional theory (DFT) calculations.


Assuntos
Hipoglicemiantes/metabolismo , Compostos de Vanádio/metabolismo , Apoproteínas/metabolismo , Biotransformação , Ácido Cítrico/metabolismo , Humanos , Hipoglicemiantes/sangue , Ácido Láctico/metabolismo , Modelos Moleculares , Albumina Sérica/metabolismo , Transferrina/metabolismo , Compostos de Vanádio/sangue
8.
Inorg Chem ; 45(5): 2156-62, 2006 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-16499378

RESUMO

This work is focused on investigating the interaction of antitumor active metallocene vanadocene dichloride (Cp2VCl2) and amino acids in aqueous solution at physiological pH. Sixteen vanadocene amino acid complexes [Cp2V(aa)][X] (aa = gly, ala, val, leu, ile, phe, his, and trp; X = Cl, PF6) were prepared and characterized on the basis of spectral measurements (EPR, MS, IR, Raman). Amino acids are coordinated to the vanadocene fragment through the oxygen atom of the carboxylic group and the nitrogen of the amino group, resulting in a five-membered chelate ring. Complexes [Cp2V(val)][PF6] and [Cp2V(ile)][PF6] have been characterized by X-ray structure analyses. It was evidenced that all prepared complexes are stable in both aqueous solutions with physiological pH and in therapeutic NaCl solutions. EPR spectra of vanadocene amino acid complexes in Krebs-Ringer solution in human blood plasma and in whole blood showed that these complexes react with the hydrogen carbonate anion present forming complex Cp2V(O2CO).


Assuntos
Aminoácidos/sangue , Aminoácidos/química , Compostos de Vanádio/sangue , Compostos de Vanádio/química , Cristalografia por Raios X , Espectroscopia de Ressonância de Spin Eletrônica , Humanos , Concentração de Íons de Hidrogênio , Estrutura Molecular , Plasma , Soluções , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho , Análise Espectral Raman , Compostos de Vanádio/síntese química , Água
9.
J Pharm Pharmacol ; 57(5): 665-9, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15901357

RESUMO

Chronic oral administration of vanadyl sulfate has recently been shown to improve the state of type 2 diabetic subjects. Mild gastrointestinal symptoms and side effects, however, have been observed in some subjects. To find safer and more effective dosages, we have developed an enteric-coated capsule containing solid vanadyl sulfate (ECC/VS), which enhances the bioavailability of vanadyl sulfate to almost double that of vanadyl sulfate solution. ECC/VS was chronically administered to treat streptozotocin-induced diabetic rats (STZ-rats), an animal model of type 1 diabetes mellitus, and an equivalent blood-glucose-lowering effect was observed at half the doses of vanadyl sulfate alone. In addition, we observed almost the same total vanadium levels in the serum after chronic administration of ECC/VS as those of vanadyl sulfate alone, suggesting that plasma vanadium levels correlate with the hypoglycaemic activity of vanadyl sulfate. These results indicate that oral ECC/VS improves the diabetic state by enhancing the uptake of vanadium in STZ-rats. These findings will be useful in designing clinical trials of vanadyl sulfate for diabetic subjects.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Compostos de Vanádio/uso terapêutico , Administração Oral , Animais , Disponibilidade Biológica , Glicemia/análise , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 1/sangue , Teste de Tolerância a Glucose , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/sangue , Masculino , Ratos , Ratos Wistar , Estreptozocina , Comprimidos com Revestimento Entérico , Compostos de Vanádio/administração & dosagem , Compostos de Vanádio/sangue
10.
J Pharm Pharmacol ; 54(5): 611-5, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12005355

RESUMO

In recent years, there have been improvements in the treatment of type 2 diabetes by oral administration of vanadyl sulfate (VOSO4, VS). The maintenance of vanadyl levels in the blood of subjects with type 2 diabetes was found to be important for the insulinomimetic activity of VS. However, owing to low bioavailability of VS and the development of mild gastrointestinal symptoms and side-effects in some subjects, it is necessary to design more effective and safer dosages of VS. After discovering that VS is absorbed more thoroughly at the ileum than at other gastrointestinal sites, we investigated the absorption processes following oral administration of VS by preparing enteric-coated capsules (ECC). Although Cmax values were unchanged by the dosage forms, Tmax and MRT values associated with the enteric-coating capsulation were prolonged when compared with those observed with use of gelatin capsules (GC). An important finding was that the bioavailability of VS from ECC (9.8%) was almost double that of VS from either GC (4.0%) or the solution (4.8%). Administration of VS-containing ECC to diabetic patients is proposed to improve vanadyl absorption over that achieved by the administration of either GC or the solution.


Assuntos
Sistemas de Liberação de Medicamentos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacocinética , Compostos de Vanádio/administração & dosagem , Compostos de Vanádio/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Hipoglicemiantes/sangue , Injeções Intravenosas , Absorção Intestinal/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Espectrometria de Massas por Ionização por Electrospray , Comprimidos com Revestimento Entérico , Fatores de Tempo , Compostos de Vanádio/sangue
11.
Fundam Clin Pharmacol ; 15(5): 313-24, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11903500

RESUMO

Vanadium pharmacokinetic parameters and oral bioavailability were determined after administration of vanadyl sulfate, an antidiabetic agent, to male Wistar rats. An optimal sampling design was used over a 21-day period; vanadium was measured in blood by atomic absorption spectrophotometry (AAS). After i.v. bolus injection (3.025 mg V/kg body weight), a three-compartment model was fitted to the data. Mean (+/- SD) half-lives were 0.90 +/- 0.56 hours, 24.8 +/- 14.5 h and 201 +/- 74 h, respectively, for the three phases observed. Vanadium clearance averaged 37.6 +/- 15.8 mL/h. Initial volume of distribution was 2.43 +/- 1.22 L/kg whereas total volume of distribution was 25.4 +/- 3.9 L/kg; these values largely exceeded body weight (i.e. 300 g), in agreement with a great uptake and retention of vanadium in tissues. After oral gavage administration (15.12 and 7.56 mg V/kg body weight), vanadium disposition was best described by a three-compartment model, with absorption appearing to occur by a zero-order rate. This process lasted 10.3 +/- 1.3 h and 10.9 +/- 1.1 h for the two dosage levels, respectively. Half-lives corresponding to the terminal log-linear part of the curve were 173.5 +/- 1.6 h and 172 +/- 6 h (Bayesian estimates). No dose-dependency was observed for any of the parameters determined. Absolute bioavailabilities, with reference to the i.v. administration, were 12.5% and 16.8% when determined from AUCmod. Bioavailability appeared to be higher than generally stated in the literature.


Assuntos
Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacocinética , Compostos de Vanádio/administração & dosagem , Compostos de Vanádio/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Hipoglicemiantes/sangue , Injeções Intravenosas , Masculino , Ratos , Ratos Wistar , Espectrofotometria Atômica , Compostos de Vanádio/sangue
12.
Can J Physiol Pharmacol ; 75(2): 83-90, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9114928

RESUMO

Controversial reports on the efficacy and possible toxicity of vanadium obtained from various studies may be attributed to differences in the method of diabetes induction and (or) to differences in animal strains. The objective of this study was to evaluate the contribution of these two factors to the effects of vanadium in the treatment of experimental diabetes. Two methods of streptozotocin induction of diabetes in rats have been used for studying the antidiabetic effects of vanadium. One involves a single intravenous injection of 60 mg/kg streptozotocin, and the other uses two subcutaneous injections of 40 mg/kg streptozotocin, to either Wistar or Sprague-Dawley rats. In a 7-week chronic study, Sprague-Dawley rats appeared to develop a more severe diabetes (indicated by higher plasma cholesterol and higher fasting plasma glucose levels) following the single intravenous injection of streptozotocin than rats made diabetic by two subcutaneous injections of streptozotocin. Irrespective of the method of diabetes induction, the responses of all the diabetic animals to chronic vanadyl sulphate treatment were similar. In an acute study, Wistar diabetic rats were more responsive than Sprague-Dawley diabetic rats to vanadyl sulphate and to lower doses (0.6 and 0.8 mmol/kg) of a new organic vanadium compound, bis(maltolato)oxovanadium(i.v.).


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Pironas/uso terapêutico , Vanadatos/uso terapêutico , Compostos de Vanádio/uso terapêutico , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Ácidos Graxos não Esterificados/sangue , Teste de Tolerância a Glucose , Insulina/sangue , Pironas/sangue , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Estreptozocina , Triglicerídeos/sangue , Vanadatos/sangue , Compostos de Vanádio/sangue , Compostos de Vanádio/toxicidade
13.
Eur J Pharmacol ; 318(1): 145-51, 1996 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-9007526

RESUMO

The effect of the antidiabetic agent vanadyl sulphate (VOSO4) on the endocrine pancreas function of normal rats was studied using the isolated pancreas preparation. A short-term (8 days) i.p. treatment (15 mg/kg per day) resulted in attenuation of high glucose-stimulated insulin release, at day 9 but also at days 19, i.e., after full recovery of appetite and weight, while blood and pancreas vanadium concentrations were still elevated. Six months of oral VOSO4 treatment (0.75 mg/ml in drinking water) resulted in elevated vanadium concentrations while glucose-stimulated insulin release was attenuated as compared to pair-fed animals. Conversely, when directly perfused in pancreas, VOSO4 potentiated glucose-stimulated insulin release. These apparently opposite effects may be related to the ability of VOSO4 to exert both peripheral insulinomimetic effects-leading to chronic reduction in insulin demand-, and a direct pancreatic insulinotropic activity.


Assuntos
Glucose/farmacologia , Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Compostos de Vanádio/farmacologia , Administração Oral , Animais , Glicemia/análise , Peso Corporal/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Técnicas In Vitro , Injeções Intraperitoneais , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Masculino , Ratos , Ratos Wistar , Compostos de Vanádio/administração & dosagem , Compostos de Vanádio/sangue
14.
Pharmacol Toxicol ; 74(2): 101-9, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8190697

RESUMO

Streptozotocin-diabetic and non-diabetic rats were given various concentrations of vanadyl sulphate in drinking water for one year. It was found that vanadyl sulphate caused significant decreases in body weight gain and plasma insulin level in non-diabetic rats, but did not significantly alter fluid and food intakes or plasma levels of glucose, triglycerides, or cholesterol. In diabetic animals, vanadyl treatment significantly alleviated or prevented the occurrence of hyperglycaemia, hypoinsulinaemia, hyperphagia, polydipsia, hyperlipidaemia, or cataract formation, but the slower body weight gain was not improved. There were gradual decreases in the intake of the compound required to correct hyperglycaemia in the values of ED50 with age of the rats. The beneficial effects of vanadyl treatment persisted 16 weeks following the withdrawal of the compound. It is concluded that vanadyl sulphate is an effective agent for chronic therapy of streptozotocin-induced diabetes in rats, and its prolonged use does not lead to the development of tolerance.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Compostos de Vanádio/uso terapêutico , Administração Oral , Animais , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Catarata/prevenção & controle , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/sangue , Insulina/sangue , Lipídeos/sangue , Masculino , Ratos , Ratos Wistar , Fatores de Tempo , Compostos de Vanádio/administração & dosagem , Compostos de Vanádio/sangue
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