Acute Effects of Vanadate Oligomers on Heart, Kidney, and Liver Histology in the Lusitanian Toadfish (Halobatrachus didactylus)

Self Cite

110

The contribution of decameric vanadate species to vanadate toxic effects in cardiac muscle was studied following an intravenous administration of a decavanadate solution (1 mM total vanadium) in Sparus aurata. Although decameric vanadate is unstable in the assay medium, it decomposes with a half-life time of 16 allowing studying its effects not only in vitro but also in vivo. After 1, 6 and 12 h upon decavanadate administration the increase of vanadium in blood plasma, red blood cells and in cardiac mitochondria and cytosol is not affected in comparison to the administration of a metavanadate solution containing labile oxovanadates. Cardiac tissue lipid peroxidation increases up to 20%, 1, 6 and 12 h after metavanadate administration, whilst for decavanadate no effects were observed except 1 h after treatment (+20%). Metavanadate administration clearly differs from decavanadate by enhancing, 12 h after exposure, mitochondrial superoxide dismutase (SOD) activity (+115%) and not affecting catalase (CAT) activity whereas decavanadate increases SOD activity by 20% and decreases (À55%) mitochondrial CAT activity. At early times of exposure, 1 and 6 h, the only effect observed upon decavanadate administration was the increase by 20% of SOD activity. In conclusion, decavanadate has a different response pattern of lipid peroxidation and oxidative stress markers, in spite of the same vanadium distribution in cardiac cells observed after decavanadate and metavanadate administration. It is suggested that once formed decameric vanadate species has a different reactivity than vanadate, thus, pointing out that the differential contribution of vanadium oligomers should be taken into account to rationalize in vivo vanadate toxicity.

Section: Introductionmentioning

confidence: 99%

“…Since 1999, our group has performed in vivo administration of decavanadate in order to understand the contribution of V10 to the toxic effects of vanadate [16][17][18][19][20][21]. A metavanadate solution not containing V10 was also administered as a comparison group of study, besides a placebo group.…”

Section: Introductionmentioning

confidence: 99%

Vanadium distribution, lipid peroxidation and oxidative stress markers upon decavanadate in vivo administration

Soares

Martins

Duarte

et al. 2007

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110

“…Decameric vanadate, composed by fused V(V) octahedra, has an ellipsoid like structure with a major and minor axis of approximately 7 and 6 Å , respectively [1]. In previous studies [2][3][4][5][6][7][8], we have demonstrated that once formed in aqueous solutions decameric vanadate decomposition is slow enough to allow studying differential effects between decameric and monomeric vanadate not only in vitro but also in vivo. Furthermore, decameric vanadate is stabilized upon interaction with cytoskeleton and membrane proteins, while it affects calcium translocation by the sarcoplasmic reticulum calcium pump and it prevents actin polymerization [9].…”

Section: Introductionmentioning

confidence: 99%

Decavanadate induces mitochondrial membrane depolarization and inhibits oxygen consumption

Soares¹,

Gutiérrez‐Merino²,

Aureliano³

2007

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Decavanadate induced rat liver mitochondrial depolarization at very low concentrations, half-depolarization with 39 nM decavanadate, while it was needed a 130-fold higher concentration of monomeric vanadate (5 lM) to induce the same effect. Decavanadate also inhibits mitochondrial repolarization induced by reduced glutathione in vitro, with an inhibition constant of 1 lM, whereas no effect was observed up to 100 lM of monomeric vanadate. The oxygen consumption by mitochondria is also inhibited by lower decavanadate than monomeric vanadate concentrations, i.e. 50% inhibition is attained with 99 nM decavanadate and 10 lM monomeric vanadate. Thus, decavanadate is stronger as mitochondrial depolarization agent than as inhibitor of mitochondrial oxygen consumption. Up to 5 lM, decavanadate does not alter mitochondrial NADH levels nor inhibit neither F O F 1 -ATPase nor cytochrome c oxidase activity, but it induces changes in the redox steady-state of mitochondrial b-type cytochromes (complex III). NMR spectra showed that decameric vanadate is the predominant vanadate species in decavanadate solutions. It is concluded that decavanadate is much more potent mitochondrial depolarization agent and a more potent inhibitor of mitochondrial oxygen consumption than monomeric vanadate, pointing out the importance to take into account the contribution of higher oligomeric species of vanadium for the biological effects of vanadate solutions.

“…However, it may become inaccessible to deoligomerization due to their stabilization upon binding to target macromolecular structures [19]. Recent work from our laboratory [20][21][22][23] demonstrated that an acute exposure to decameric vanadate species, but not exposure to monomeric vanadate, induces changes on vanadium accumulation and in overall stress markers. Altogether, these observations reveal that decameric vanadate plays an important role in the evaluation of vanadium (V) toxicity in biological systems [17].…”

Section: Introductionmentioning

confidence: 99%

Decavanadate interactions with actin: Inhibition of G-actin polymerization and stabilization of decameric vanadate

Ramos

Manuel

Tiago

et al. 2006

101

Decameric vanadate species (V10) inhibit the rate and the extent of G-actin polymerization with an IC50 of 68 ± 22 lM and 17 ± 2 lM, respectively, whilst they induce F-actin depolymerization at a lower extent. On contrary, no effect on actin polymerization and depolymerization was detected for 2 mM concentration of ''metavanadate'' solution that contains ortho and metavanadate species, as observed by combining kinetic with 51 V NMR spectroscopy studies. Although at 25°C, decameric vanadate (10 lM) is unstable in the assay medium, and decomposes following a first-order kinetic, in the presence of G-actin (up to 8 lM), the half-life increases 5-fold (from 5 to 27 h). However, the addition of ATP (0.2 mM) in the medium not only prevents the inhibition of G-actin polymerization by V10 but it also decreases the half-life of decomposition of decameric vanadate species from 27 to 10 h. Decameric vanadate is also stabilized by the sarcoplasmic reticulum vesicles, which raise the half-life time from 5 to 18 h whereas no effects were observed in the presence of phosphatidylcholine liposomes, myosin or G-actin alone. It is proposed that the ''decavanadate'' interaction with G-actin, favored by the G-actin polymerization, stabilizes decameric vanadate species and induces inhibition of G-actin polymerization. Decameric vanadate stabilization by cytoskeletal and transmembrane proteins can account, at least in part, for decavanadate toxicity reported in the evaluation of vanadium (V) effects in biological systems.