Development of a novel resin with antimicrobial properties for dental application

The adhesion of biofilm on dental prostheses is a prerequisite for the occurrence of oral diseases. Objective: To assess the antimicrobial activity and the mechanical properties of an acrylic resin embedded with nanostructured silver vanadate (β-AgVO3). Material and Methods: The minimum inhibitory concentration (MIC) of β-AgVO3 was studied in relation to the species Staphylococcus aureus ATCC 25923, Streptococcus mutans ATCC 25175, Pseudomonas aeruginosa ATCC 27853, and Candida albicans ATCC 10231. The halo zone of inhibition method was performed in triplicate to determine the inhibitory effect of the modified self-curing acrylic resin Dencor Lay - Clássico®. The surface hardness and compressive strength were examined. The specimens were prepared according to the percentage of β-AgVO3 (0%-control, 0.5%, 1%, 2.5%, 5%, and 10%), with a sample size of 9x2 mm for surface hardness and antimicrobial activity tests, and 8x4 mm for the compression test. The values of the microbiologic analysis were compared and evaluated using the Kruskal-Wallis test (α=0.05); the mechanical analysis used the Shapiro-Wilk's tests, Levene's test, ANOVA (one-way), and Tukey's test (α=0.05). Results: The addition of 10% β-AgVO3 promoted antimicrobial activity against all strains. The antimicrobial effect was observed at a minimum concentration of 1% for P. aeruginosa, 2.5% for S. aureus, 5% for C. albicans, and 10% for S. mutans. Surface hardness and compressive strength increased significantly with the addition of 0.5% β-AgVO3 (p<0.05). Higher rates of the nanomaterial did not alter the mechanical properties of the resin in comparison with the control group (p>0.05). Conclusions: The incorporation of β-AgVO3 has the potential to promote antimicrobial activity in the acrylic resin. At reduced rates, it improves the mechanical properties, and, at higher rates, it does not promote changes in the control. .

Inhibitory and stimulating effect of magnesium on vanadate-induced lipid peroxidation under in vitro conditions.

The behaviour of Mg related to vanadium(V)-induced lipid peroxidation (LPO) under in vitro conditions was examined. The studies performed on the liver supernatants (LS) obtained from control, sodium metavanadate-intoxicated, and sodium metavanadate-magnesium sulphate-administered male Wistar rats revealed and confirmed the pro-oxidative potential of V. Simultaneously, they indicated that the improved Mg status may be one of the mechanisms by which the treatment with this element may contribute to reduction of oxidative stress under the conditions of vanadate exposure. On the other hand, the results confirmed that Mg may also stimulate LPO and demonstrated that the incubation conditions and the experimental treatment of the rats from which the liver supernatants were obtained affect the intensity of the examined free radical process.

Efeito do sulfato de vanadil sobre o comprometimento metabólico muscular induzido pela imobilização de membro posterior de ratos / Efecto del sulfato de vanadil sobre comprometimiento metabólico muscular inducido por la inmovilización del miembro posterior en ratones / Effect of the vanadyl sulphate on the muscular metabolic compromising induced by immobilization of posterior limb of rats

A proposta deste trabalho foi avaliar o efeito do sulfato de vanadil (SV) no perfil metabólico muscular de membro posterior imobilizado de ratos. Ratos Wistar foram divididos nos grupos (n = 6): controle (C), imobilizado em posição neutra do tornozelo (I), tratado com sulfato de vanadil (SV, 0,25mM, VO) e imobilizado tratado com SV (I + SV) durante sete dias. Após o período experimental, foram avaliadas as reservas de glicogênio (RG) dos músculos sóleo (S), gastrocnêmio branco (GB) e vermelho (GV), tibial anterior (TA) e extensor longo dos dedos (ELD), além do peso do S e ELD. A análise estatística foi realizada pela ANOVA seguida pelo teste de Tukey (p < 0,05). No grupo SV, os resultados mostraram elevação significativa nas RG (S 110 por cento, GB 71 por cento, GV 85 por cento, TA 125 por cento, EDL 108 por cento) e no peso (S 9 por cento, EDL 11 por cento). A imobilização reduziu significativamente as RG (S 31,6 por cento, GB 56,6 por cento, GV 39,1 por cento, ELD 41,7 por cento, TA 45,2 por cento) e peso (S 34,2 por cento e ELD 27 por cento); já no grupo I + SV, houve o aumento das RG em todos os músculos (S 211 por cento, GB 115 por cento, GV 148 por cento, ELD 161,9 por cento, TA 147 por cento), além de impedir a perda de peso do S (75 por cento) e ELD (46 por cento). O tratamento com sulfato de vanadil promoveu elevação nas reservas de glicogênio do grupo controle e imobilizado, além de impedir a perda de peso, demonstrando que seu efeito insulino-mimético é representado pela ação glicogênica associado a uma possível ação anticatabólica.

The purpose of this study was to evaluate the metabolic performance of immobilized skeletal muscle in rats treated with vanadyl sulphate. Male Wistar rats were divided in groups (n = 6): control (C), immobilized (I), treated with vanadyl sulphate (VS, 0,25 mM) and immobilized treated with vanadyl sulphate (I + VS) during seven days. The concentration of vanadyl sulphate diluted in water was 0,25 mM. After experimental stage, the glycogen content (GC) was evaluated in soleus (S), white gastrocnemius (WG), red gastrocnemius (RG), tibialis anterior (TA) and extensor digitorum longus (EDL) muscles, besides S and EDL weight. The statistical analysis was realized by the ANOVA followed by Tukey test (p < 0,05). In VS group, the results showed a significant increase in GC (S 110 percent, WG 71 percent, RG 85 percent, TA 125 percent, EDL 108 percent) and in the weight (S 9 percent, EDL 11 percent). The immobilization reduced significantly the GC (S 31.6 percent, WG 56.6 percent, RG 39.1 percent, EDL 41.7 percent, TA 45.2 percent) and weight (S 34.2 percent and ELD 27 percent), and in I + VS group, there was a increase of the GC in all muscles (S 211 percent, WG 115 percent, RG 148 percent, EDL 161.9 percent, TA 147 percent), besides hindering the weight loss in S (75 percent) and EDL (46 percent). The vanadyl sulphate treatment promoted an increase in the glycogen content of control and immobilized groups, besides hindering the weight loss, showing that the insulino-mimetic effect is represented by glycogenic action associate to a possible anti-catabolic action.

La propuesta de este trabajo ha sido la de evaluar el efecto del sulfato de vanadil (SV) en el perfil metabólico muscular de miembro posterior inmovilizado de ratones. Ratones Wistar fueron divididos en grupos (n = 6): control (C), inmovilizado en posición neutra de tobillo (I), tratado con sulfato de vanadil (SV, 0,25mM, VO) e inmovilizado tratado con SV (I + SV) durante 7 días. Después del periodo experimental, fueron evaluadas las reservas de glicógeno (RG) de los músculos soleo (S), gastrocnemio blanco (GB) y colorado (GV), tibial anterior (TA) y extensor largo de los dedos (ELD), además del peso de S y ELD. El análisis estadístico fue realizado por ANOVA seguido del test de Tukey (p < 0,05). En el grupo SV, los resultados mostraron elevación significativa en las RG (S 110 por ciento, GB 71 por ciento, GV 85 por ciento, TA 125 por ciento, EDL 108 por ciento) y en el peso (S 9 por ciento, EDL 11 por ciento). La inmovilización redujo significativamente las RG (S 31,6 por ciento, GB 56,6 por ciento, GV 39,1 por ciento, ELD 41,7 por ciento, TA 45,2 por ciento) y peso (S 34,2 por ciento e ELD 27 por ciento), por otro lado en el grupo I + SV, hubo aumento de las RG en todos los músculos (S 211 por ciento, GB 115 por ciento, GV 148 por ciento, ELD 161,9 por ciento, TA 147 por ciento), además de impedir la pérdida de peso de S (75 por ciento) y ELD (46 por ciento). El tratamiento con sulfato de vanadil promovió una elevación en las reservas de glicógeno del grupo control e inmovilizado, además de impedir la pérdida de peso, lo que demuestra que su efecto insulina mimético está representado por la acción glicogénica asociado a una posible acción anticatabólica.

Hypoglycemic effects of vanadium on alloxan monohydrate induced diabetic dogs

The hypoglycemic effects after oral administration of vanadium have been studied previously in many species such as rats, mice and even humans. However, there has been no prior report on the glucose lowering effect of vanadium on diabetic dogs. Therefore, the purpose of this study was to evaluate the hypoglycemic effects of oral vanadium on diabetic dogs. Diabetes mellitus in the dogs studied was induced by alloxan monohydrate intravenous injection. The dogs were divided into two groups, one was the diabetic control (DC) group (n = 4) and the other was the vanadium treated (DV) group (n = 6). Fresh water was supplied to the dogs in the DC group, but sodium metavanadate solution (0.1~0.2 mg/ml) was given to the dogs in DV group from one week after the alloxan injection. The fasting glucose levels, fructosamine and serum chemistry profiles were compared between the two groups weekly for three weeks. The fasting blood glucose levels in DV group were significantly lower than those in the DC group (p < 0.01). Fructosamine levels in the DV group were also lower than those in the DC group (p < 0.05). The serum chemistry profiles were not significantly different in comparisons between the two groups. However, the cholesterol levels were significantly lower in the DV group compared to the DC group (p < 0.05). Our findings showed that oral vanadium administration had a hypoglycemic effect on chemically induced diabetic dogs.

Tyrosine phosphatase and cytochrome P450 activity are critical in regulating store-operated calcium channels in human fibroblasts

Diverse signaling pathways have been proposed to regulate store-operated calcium entry (SOCE) in a wide variety of cell types. However, it still needs to be determined if all of these known pathways operate in a single cell type. In this study, we examined involvement of various signaling molecules in SOCE using human fibroblast cells (HSWP). Bradykinin (BK)-stimulated Ca2+ entry, previously shown to be via SOCE, is enhanced by the addition of vanadate, an inhibitor of tyrosine phosphatases. Furthermore, SOCE is regulated by cytochrome P-450, as demonstrated by the fact that the products of cytochrome P-450 activity (14,15 EET) stimulated SOCE while econazole, an inhibitor of cytochrome P450, suppressed BK-stimulated Ca2+ entry. In contrast, Ca2+ entry was unaffected by the guanylate cyclase inhibitor LY83583, or the membrane permeant cyclic GMP analog 8-bromo-cyclic GMP (8-Br-cGMP). Neither nitric oxide donors nor phorbol esters affected BK-stimulated Ca2+ entry. SOCE in HSWP cells is primarily regulated by tyrosine phosphorylation and the cytochrome P-450 pathway, but not by cyclic GMP, nitric oxide, or protein kinase C. Thus, multiple pathways do operate in a single cell type leading to the activation of Ca2+ entry and some of these signaling pathways are more prominently involved in regulating calcium entry in different cell types.

Amelioration of altered antioxidant status and membrane linked functions by vanadium and Trigonella in alloxan diabetic rat brains.

Trigonella foenum graecum seed powder (TSP) and sodium orthovanadate (SOV) have been reported to have antidiabetic effects. However, SOV exerts hypoglycemic effects at relatively high doses with several toxic effects. We used low doses of vanadate in combination with TSP and evaluated their antidiabetic effects on anti-oxidant enzymes and membrane-linked functions in diabetic rat brains. In rats, diabetes was induced by alloxan monohydrate (15 mg/100 g body wt.) and they were treated with 2 IU insulin, 0.6 mg/ml SOV, 5% TSP and a combination of 0.2 mg/ml SOV with 5% TSP for 21 days. Blood glucose levels, activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), Na+/K+ ATPase, membrane lipid peroxidation and fluidity were determined in different fractions of whole brain after 21 days of treatment. Diabetic rats showed high blood glucose (P less than 0.001), decreased activities of SOD, catalase and Na+/K+ ATPase (P less than 0.01, P less than 0.001 and P less than 0.01), increased levels of GPx and MDA (P less than 0.01 and P less than 0.001) and decreased membrane fluidity (P less than 0.01). Treatment with different antidiabetic compounds restored the above-altered parameters. Combined dose of Trigonella and vanadate was found to be the most effective treatment in normalizing these alterations. Lower doses of vanadate could be used in combination with TSP to effectively counter diabetic alterations without any toxic effects.

Phospholipase D is involved in oxidative stress-induced migration of vascular smooth muscle cells via tyrosine phosphorylation and protein kinase C

Oxidative stress has been implicated in mediation of vascular disorders. In the presence of vanadate, H2O2 induced tyrosine phosphorylation of PLD1, protein kinase C-a (PKC-a), and other unidentified proteins in rat vascular smooth muscle cells (VSMCs). Interestingly, PLD1 was found to be constitutively associated with PKC-a in VSMCs. Stimulation of the cells by H2O2 and vanadate showed a concentration-dependent tyrosine phosphorylation of the proteins in PLD1 immunoprecipitates and activation of PLD. Pretreatment of the cells with the protein tyrosine kinase inhibitor, genistein resulted in a dose-dependent inhibition of H2O2-induced PLD activation. PKC inhibitor and down-regulation of PKC abolished H2O2-stimulated PLD activation. The cells stimulated by oxidative stress (H2O2) caused increased cell migration. This effect was prevented by the pretreatment of cells with tyrosine kinase inhibitors, PKC inhibitors, and 1-butanol, but not 3-butanol. Taken together, these results suggest that PLD might be involved in oxidative stress-induced migration of VSMCs, possibly via tyrosine phosphorylation and PKC activation.

Activation of epidermal growth factor receptor is responsible for pervanadate-induced phospholipase D activation

Pervanadate, a complex of vanadate and H2O2, has an insulin mimetic effect, and acts as an inhibitor of protein tyrosine phosphatase. Pervanadate-induced phospholipase D (PLD) activation is known to be dependent on the tyrosine phosphorylation of cellular proteins and protein kinase C (PKC) activation, and yet underlying molecular mechanisms are not clearly understood. Here, we investigated the signaling pathway of pervanadate-induced PLD activation in Rat2 fibroblasts. Pervanadate increased PLD activity in dose- and time- dependent manner. Protein tyrosine kinase inhibitor, genistein, blocked PLD activation. Interestingly, AG-1478, a specific inhibitor of the tyrosine kinase activity of epidermal growth factor receptor (EGFR) blocked not only the PLD activation completely but also phosphorylation of p38 mitogen- activated protein kinase (MAPK). However, AG-1295, an inhibitor specific for the tyrosine kinase activity of pletlet drived growth factor receptor (PDGFR) did not show any effect on the PLD activation by pervanadate. We further found that pervanadate increased phosphorylation levels of p38, extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK). SB203580, a p38 MAPK inhibitor, blocked the PLD activation completely. However, the inhibitions of ERK by the treatment of PD98059 or of JNK by the overexpression of JNK interacting peptide JBD did not show any effect on pervanadate-induced PLD activation. Inhibition or down-regulation of PKC did not alter the pervanadate-induced PLD activation in Rat2 cells. Thus, these results suggest that pervanadate-induced PLD activation is coupled to the transactivation of EGFR by pervanadate resulting in the activation of p38 MAP kinase.

Regulation of chicken protein tyrosine phosphatase 1 and human protein tyrosine phosphatase 1B activity by casein kinase II- and p56lck-mediated phosphorylation

Protein tyrosine phosphorylation and dephosphorylation are important in the regulation of cell proliferation and signaling cascade. In order to examine whether phosphatase activity of CPTP1 and HPTP1B, typical nontransmembrane protein tyrosine phosphatase, could be controlled by phosphorylation, affinity-purified PTPs were phosphorylated by CKII and p56lck in vitro. Phosphoamino acid analysis revealed that CPTP1 was phosphorylated on both serine and threonine residues by CKII, and tyrosine residue by p56lck. Phosphatase activity of CPTP1 was gradually increased by three-fold concomitant with phosporylation by CKII. Phosphorylation of HPTP1B by CKII resulted in quick two-fold enhancement of its phosphatase activity within 5 min of incubation and remained in that state. In the presence of CKII inhibitor, heparin or poly(Glu.Tyr), both phosphorylation and enhancement of phosphatase activity of CPTP1 and HPTP1B were mostly blocked. p56lck catalyzed tyrosine phosphorylation of CPTP1 and HPTP1B was only observed by inhibiting the intrinsic tyrosine phosphatase activity. Taken together, these results indicate that CPTP1 or HPTP1B possesses a capability to regulate its phosphatase activity through phosphorylation processes and may participate in the cellular signal cascades.

Modulation of mRNA levels of liver arginase by insulin and vanadate in experimental diabetes.

This work was carried out to study the modulation of arginase expression in experimental diabetes. Here, we have demonstrated that liver arginase activity and mRNA levels increased significantly in diabetic condition. Insulin treatment reverses the increased activity and mRNA levels nearly to the control values. The reversal effects of vanadate are found to be similar to that of insulin and this observation further reiterates the insulin-like effects of vanadate. ELISA and slot blot assay observations are consistent with biochemical measurements of enzyme activity. These results show an increase in arginase activity and mRNA levels in diabetes and decrease in treated animals may be due to the transcriptional regulation of arginase gene.

Effect of antidiabetic compounds on glyoxalase I activity in experimental diabetic rat liver.

The activity of glyoxalase I from the soluble fraction of diabetic rat liver was found to decrease as compared to the control. Sodium orthovanadate in drinking water and Trigonella foenum graecum seed powder when administered to these diabetic animals were found to reverse the activity of glyoxalase I to control values. A combination of the above two antidiabetic compounds showed a better reversal. Vanadate and Trigonella seed powder treatment separately to diabetic rats also normalized hyperglycemia together with glyoxalase I activity. A combination of vanadate and Trigonella seed powder also restored the other general parameters of the diabetic animals.

Effects of vanadate, insulin and fenugreek (Trigonella foenum graecum) on creatine kinase levels in tissues of diabetic rat.

The in vivo effects of insulin, and other insulino mimetic agents like vanadate and fenugreek (T. foenum graecum) were followed on the changes in the activities of creatine kinase in heart, skeletal muscle and liver of experimental diabetic rats. As compared to control rats, creatine kinase activities were found to decrease significantly in the tissues during experimental diabetes. All the antidiabetic compounds used namely, insulin, vanadate and Fenugreek seed powder normalised the decreased activities to almost control values. The effects of insulin and vanadate were comparable in restoring normoglycemia and the creatine kinase activities.

Modulation of some gluconeogenic enzyme activities in diabetic rat liver and kidney: effect of antidiabetic compounds.

The effects of insulin, sodium orthovanadate and a hypoglycemic plant material, Trigonella foenum graecum (fenugreek) seed powder were studied on the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in diabetic liver and kidney. The significantly increased activities of the two enzymes during diabetes in liver and kidney were found to be lowered to almost control values by the use of the antidiabetic compounds. Diabetic liver exhibited a much greater increase in the activities of the two enzymes than diabetic kidney. The highest percentage of reversal to normal values was seen using the combination of vanadate and Trigonella seed powder. The lowered rate of growth of the animals as well as the increased blood sugar were reversed almost to the control levels by the Trigonella seed powder and vanadate treatment. The inclusion of the Trigonella seed powder overcame the toxicity of vanadium encountered when it was given alone as insulin mimetic agent. Much lower levels of vanadate were needed when it was given in combination with Trigonella seed powder. Their combined effects were better at restoring the above parameters than those induced by insulin administration.

Kinetic studies on the membrane form of intestinal alkaline phosphatase

We have purified different membrane and soluble forms of alkaline phosphatase from human placenta and bovine intestine. The enzymes will be used as markers in immunoconjugates and/or as model for membrane enzyme studies. The membrane formof alkaline phosphatase extracted from bovine intestine was purified on Q-Sepharose and on L-histidyldiazobenzylphosphonic acid-agarose columns to remove phosphodiesterase activity. The purified enzyme had a molecular mass of 61 kDa, Km of 1208 µM, and Vmax 240 µmol pNP/min when assayed in 1 M diethanolamine, 0.5 mM MgCl2 buffer, pH 9.8, containing 10 to 2250 µM of pNPP at 37§C. In the present investigation we studied the effect of salts and inositol derivatives on this enzyme activity, which was found to depend on 0.5 mM Mg2+, and to be fully inhibited by 1.2 mM Hg2+. Vanadate (0.5 mM) and Zn2+ (0.5 mM) reduced the Km value by 43 percent and 84 percent, respectively. Inositol (2 mM) and inositol-2-monophosphate (2 mM) reduced the activity by 23 percent and 17 percent. Inositol-1-monophosphate (0.5 mM) and cyclic-inositol-(1:2)-monophosphate (0.5 mM) enhanced their Km value by at least 30 percent compared to p-nitrophenylphosphate

Stimulation of Cl- secretion by AlF4- and vanadate in T84 cells

We investigated the mechanism of Cl- secretion by fluoroaluminate(AlF4-) and sodium orthovanadate(vanadate) using the human colonic T84 cell line. T84 cell monolayers grown on collagen-coated filters were mounted in Ussing chambers to measure short circuit current(ISC). Serosal addition of AlF4- or vanadate to T84 monolayers produced a sustained increase in ISC. Removal of Ca2+ from the serosal bathing solution partially inhibited AlF4-(-)and vanadate-induced ISC, and readministration of Ca2+ restored AlF4-(-)and vanadate-induced ISC. Carbachol application in the presence of forskolin, AlF4- or vanadate induced a synergistic increase of ISC. Forskolin and vanadate significantly increased cellular cAMP level, while carbachol and AlF4- did not. Carbachol, AlF4- and vanadate significantly increased [Ca2+]i. After Na+ in mucosal bathing solution was replaced with K+, and the mucosal membrane of T84 cell was permeabilized with amphotericin B, AlF4-, vanadate, and carbachol increased K+ conductance, but forskolin did not. After sodium chloride in serosal bathing solution was replaced with sodium gluconate and the serosal membrane was permeabilized with nystatin, forskolin, AlF4-, and vanadate increased Cl- conductance, but carbachol did not. AlF4-(-)induced ISC was remarkably inhibited by the pretreatment of pertussis toxin(2 micrograms/ml) for 2 hours. These results indicate that AlF4- and vanadate can increase Cl- secretion via simultaneous stimulation of Cl- channel and K+ channel in T84 cells. However, the AlF4- action is mostly attributed to stimulation of pertussis toxin-sensitive G-proteins, whereas the vanadate action mostly results from G protein-independent mechanisms.

Insulin-like effects of bis-glycinato oxovanadium (IV) complex on experimental diabetic rats.

The insulin-like activity of bis-glycinato oxovanadium (IV) complex on experimental diabetes has been studied. Rats made diabetic with streptozotocin, after one month, were fed ad libitum with bis-glycinato oxovanadium (IV) complex (30 mg/100 ml) for fifteen days. The altered blood glucose, urea, cholesterol, triglycerides, liver glycogen and the activities of liver enzymes such as hexokinase, lactate dehydrogenase and fructose-1, 6-bisphosphatase, were reverted to normal levels in bis-glycinato oxovanadium (IV) complex treated diabetic rats, thereby suggesting for the insulin-mimetic effect of bis-glycinato oxovanadium (IV) in experimental diabetes.

Calcium homeostasis in Trypanosoma cruzi

By using the fluorescent Ca2+ indicator fura 2, submicromolar levels of intracellular Ca2+ have been detected in Trypanosoma cruzi different stages. The intracellular transport mechanisms involved in maintaining Ca2+ homeostasis in T. cruzi have been characterized by measuring Ca2+ transport in digitonin-permeabilized cells. Two intracellular calcium transport systems have been detected. Ca2+ uptake by the mitochondria occurs by an electrophoretic mechanism, is inhibited by antimycin A, FCCP, and ruthenium red, and stimulated by respiratory substrates, phosphate and acetate. This pool has a high capacity and low affinity for Ca2+ and is able to buffer external Ca2+ at concentrations in the range of 0.6-0.7 microM. Ca2+ uptake by the endoplasmic reticulum is inhibited by high concentrations of vanadate and anticalmodulin agents, and stimulated by ATP. This pool has a low capacity and a high affinity for Ca2+ and is able to buffer external Ca2+ at concentrations in the range of 0.05-1.0 microM. In addition, calmodulin has been purified from T. cruzi epimastigotes and shown to stimulate the homologous plasma membrane Ca(2+)-ATPase and cyclic-AMP phosphodiesterase. The gene encoding this protein has been cloned and sequenced and shown to have a great homology to mammalian calmodulin. The role of the plasma membrane of T. cruzi in the regulation of [Ca2+]i has been studied using fura 2-loaded epimastigotes or plasma membrane vesicles prepared from epimastigotes. Plasma membrane vesicles transport Ca2+ in the presence of Mg2+ and have a high affinity, vanadate-sensitive (Ca(2+)-Mg2+)-ATPase with an apparent Km for free Ca2+ of 0.3 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of vanadate on tryptophan metabolism in streptozotocin diabetic rats.

Administration of sodium orthovanadate (0.3 mg/ml) through drinking water for 20 days to streptozotocin-induced diabetic rats resulted in reversal of markedly elevated activities of some of the key enzymes of tryptophan-niacin pathway, viz. hepatic and renal aminocarboxymuconate semialdehyde decarboxylase and hepatic tryptophan oxygenase, to normal levels without restoring the elevated blood sugar level to normal state. However vanadate administration to normal rats did not cause any significant change.

Effects of vanadate on vascular contractility and membrane potential in the rabbit aorta

Isolated rabbit aortic ring with intact endothelial cell preparations precontracted with NE (10(-7) M) were relaxed by vanadate in a dose dependent manner (from 0.2 to 2 mM). Application of vanadate and ACh during the tonic phase of high K+(100 mM)-induced contraction showed a slight relaxation in contrast to that in NE-induced contraction, but sodium nitroprusside (10 microM) more effectively relaxed the aortic ring preparations in high K+ contraction than that of vanadate. Vanadate-induced relaxation in NE-contracted aortic rings was reversed by application of BaCl2 (50 microM) or glibenclamide (10 microM). Furthermore, Vanadate hyperpolarized membrane potential of smooth muscle cells in endothelium-intact aortic strips and this effect was abolished by application of glibenclamide. The above results suggest that vanadate release EDHF (Endothelium-Derived Hyperpolarizing Factor), in addition to EDRF (Endothelium-Derived Relaxing Factor) from endothelial cell. This EDHF hyperpolarize the smooth muscle cell membrane potential via opening of the ATP-sensitive K+ channel and close a voltage dependent Ca++ channel. So it is suggested that the vanadate-induced relaxation of rabbit thoracic aortic rings may be due to the combined effects of EDRF and EDHF.

Increase in alpha-glycerophosphate dehydrogenase and other oxidoreductase activities of hepatic mitochondria on administration of vanadate to the rat.

Liver mitochondria isolated from vanadate-administered rats showed increased (20-25%) rates of oxidation of both NAD(+)-linked substrates and succinate. Respiratory control index and ADP/O were unaffected by the treatment. Dormant and uncoupler-stimulated ATPase activity also was not affected by vanadate administration. Membrane-bound, electron-transport-linked dehydrogenase activities (both NAD(+)- and succinate-dependent) increased by 15-20% on vanadate treatment. Mitochondrial alpha-glycerophosphate dehydrogenase activity increased by 50% on vanadate administration. The above effects of vanadate on oxidoreductase activities could be prevented by the prior administration of antagonists to alpha-adrenergic receptors. Substrate-dependent H2O2 generation by mitochondria also showed an increase on vanadate administration.