Decavanadate toxicology and pharmacological activities: V10 or V1, both or none?

This review covers recent advances in the understanding of decavanadate toxicology and pharmacological applications. Toxicological in vivo studies point out that V10 induces several changes in several oxidative stress parameters, different from the ones observed for vanadate (V1). In in vitro studies with mitochondria, a particularly potent V10 effect, in comparison with V1, was observed in the mitochondrial depolarization (IC50 = 40 nM) and oxygen consumption (99 nM). It is suggested that mitochondrial membrane depolarization is a key event in decavanadate induction of necrotic cardiomyocytes death. Furthermore, only decavanadate species and not V1 potently inhibited myosin ATPase activity stimulated by actin (IC50 = 0.75 M) whereas exhibiting lower inhibition activities for Ca2+-ATPase activity (15 M) and actin polymerization (17 M). Because both calcium pump and actin decavanadate interactions lead to its stabilization, it is likely that V10 interacts at specific locations with these proteins that protect against hydrolysis but, on the other hand, it may induce V10 reduction to oxidovanadium(IV). Putting it alltogether, it is suggested that the pharmacological applications of V10 species and compounds whose mechanism of action is still tobe clarified might involve besides V10 and V1 also vanadium(IV) species

Decavanadate: a journey in a search of a role

Currently, efforts have been directed towards using decavanadate as a tool for the understanding of several biochemical processes such as muscle contraction, calcium homeostasis, in vivo changes of oxidative stress markers, mitochondrial oxygen consumption, mitochondrial membrane depolarization, actin polymerization and glucose uptake, among others. In addition, studies have been conducted in order to make vanadium available and safe for clinical use, for instance with decavanadate compounds that present interesting pharmacological properties, eventually useful for the treatment of diabetes. Here, recent contributions of decavanadate to the effects of vanadium in biological systems, not only in vitro, but also in vivo, are analysed

Decavanadate contribution to vanadium biomarkers

The levels of vanadium in urine and blood can be used as biomarkers of exposure, but the mechanism of vanadium toxicity is of major relevance in order to understand how biomarkes can be valuable. Our research group has performed in vivo and in vitro studies using fish and rat models to analysed and compare the toxicity effects induce by vanadium(V) species in the forms of vanadate (V1) and decavanadate (V10). Vanadium toxicological studies often disregarded the formation of decameric vanadate species (V10) known to interact, in vitro, with high-affinity with many proteins such as myosin, actin and sarcoplasmic reticulum calcium pump. Among different experimental in vivo conditions, it was analysed different: (i) mode of administration; (ii) fish species; (iii) metal concentration (1 and 5 mM); (iv) tissues; (v) subcellular fractions ; (vi) exposure time and particularly different metal ionic species, such as V1 and V10. It was observed that‘‘decavanadate’’ promote different effects than other vanadate oligomers in catalase activity, glutathione content, lipid peroxidation, mitochondrial superoxide anion production and vanadium accumulation. Moreover, in in vitro studies using fish and rat liver mitochondria, it was observed that decavanadate impared respiration by depolarization of the mitochondrial membrane, wich altered the redox state of complex III. Putting it all together, it is suggested that decavanadate species are much more effective than monomeric vanadate species in inducing changes in several biomarkers. By changing mitochondrial functioning decavanadate migh provoke ROS formation, but further studies are needed to understand V10 contribution to vanadium biomarkers.info:eu-repo/semantics/publishedVersio

A bioquímica na sociedade

A Química Biológica, também conhecida por Bioquímica, é uma área do conhecimento que é cada vez mais importante nas sociedades contemporâneas. A Bioquímica, é uma ciência interdisciplinar que utiliza estratégias e métodos de muitas outras, desde a Física à Farmacologia

A química da vida

A Bioquímica ou Química da Vida é uma ciência interdisciplinar que utiliza estratégias e métodos de todas as Ciências Exactas e Naturais. Nos últimos 10 anos, foram catorze os prémios Nobel da Química, Fisiologia e Medicina que foram atribuídos na área da Bioquímica o que reflecte a importância desta área de conhecimento nas Sociedades contemporâneas. A Química da Vida não se reduz apenas ao estudo dos compostos orgânicos, tais como os açúcares, lipidos ou proteínas mas também ao estudo da função de iões metálicos como por exemplo o Ca2+, Na+ ou Fe2+ que estão envolvidos em processos biológicos essenciais, tais como a contracção muscular, a transmissão do impulso nervoso, a mineralização do tecido ósseo ou o transporte de oxigénio. É a lei do Oportunismo (utilização de um mesmo material ou processo para vários fins), pois os seres vivos aprenderam a utilizar, a partir dos minerais, vários elementos metálicos que se tornaram essenciais, como os agregados ferro-enxofre (da pirite) para fazerem parte de proteínas (as metaloproteínas) que catalizam reacções químicas que ocorrem nas células. Outras metaloproteínas incluem outros metais tais como cobre, molibdénio, vanádio que são igualmente essenciais para a Química da Vida. Pequenas moléculas, são também indispensáveis para a homeostasia celular, por exemplo os iões carbonato e os iões fosfato, responsáveis pela estabilização do valor de pH fisiológico (próximo de 7.0). Mas, mais importante ainda é a molécula de ATP (Á-tê-pês é a conta que Deus fez), a moeda de troca energética para todos os processos celulares. Por dia, um Homo sapiens com cerca de 70 kg produz cerca de 700 kg de ATP. Dá para acreditar? Tudo o que comemos, acúçares, proteínas, lipidos “arde” nas mitocôndrias produzindo ATP necessário para todos os processos celulares (contracção muscular, sinalização celular, etc) e água (tinha que meter água!). É a lei do Menor Esforço ou Cera (fazer o máximo com um mínimo de estratégias) juntamente com a Lei da Reciclagem: tudo, ou quase tudo, é reciclado no euro Bioquímico: o ATP

Decavanadate interactions with sarcoplasmic reticulum calcium pump

Although not stable, once formed, decameric vanadate (V10) disintegration is in general slow enough to allow the study of its effects even in the micromolar range. Besides, it may become inaccessible to decomposition due to their specific interaction upon target proteins such as the Ca2+-ATPase from sarcoplasmic reticulum (SR). Characterization of the vanadate solutions and interactions with compounds containing phosphate as well as with the SR Ca2+-ATPase was analysed by 51V NMR spectroscopy. Vanadate is a well known inhibitor of this E1E2 phosphohydrolases and it as been used as a probe in the study of the structure and in the function of the protein. Decameric vanadate species also interact with the SR Ca2+-ATPase but clearly differs from monomeric vanadate by inhibiting sarcoplasmic reticulum calcium translocation at different calcium gradient conditions, coupled or not to ATP hydrolysis. Vanadium(IV) and (V) complexes, some known to have insulinomimetic properties, also inhibit the calcium ATPase activity, although at a lower extend than V10