Decavanadate effects in biological systems Manuel Aureliano * , Ricardo M.C. Ga ˆndara CBME, Dept. Quı ´mica e Bioquı ´mica, FCT, Universidade do Algarve, 8005-139 Faro, Portugal Received 27 January 2005; received in revised form 23 February 2005; accepted 25 February 2005 Available online 23 March 2005 Abstract Vanadium biological studies often disregarded the formation of decameric vanadate species known to interact, in vitro, with high-affinity with many proteins such as myosin and sarcoplasmic reticulum calcium pump and also to inhibit these biochemical systems involved in energy transduction. Moreover, very few in vivo animal studies involving vanadium consider the contribution of decavanadate to vanadium biological effects. Recently, it has been shown that an acute exposure to decavanadate but not to other vanadate oligomers induced oxidative stress and a different fate in vanadium intracellular accumulation. Several markers of oxida- tive stress analyzed on hepatic and cardiac tissue were monitored after in vivo effect of an acute exposure (12, 24 h and 7 days), to a sub-lethal concentration (5 mM; 1 mg/kg) of two vanadium solutions (‘‘metavanadate’’ and ‘‘decavanadate’’). 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, whereas both solutions seem to equally depress reactive oxygen species (ROS) production as well as total intracellular reducing power. Vanadium is accumulated in mitochondria in par- ticular when ‘‘decavanadate’’ is administered. These recent findings, that are now summarized, point out the decameric vanadate species contributions to in vivo and in vitro effects induced by vanadium in biological systems. Ó 2005 Elsevier Inc. All rights reserved. Keywords: Decavanadate; Oxidative stress; Myosin; SR calcium pump 1. Introduction Vanadium was found in commercial ATP and redis- covered for biology as a muscle inhibitor factor (MIF) and Na + ,K + -ATPase inhibitor [1–3]. Currently, vana- dium is used as inhibitor of E1–E2 ion transport ATP- ases [4] being a useful tool to mimics the transition states of phosphoryl transfer reactions [5]. It has been reported that vanadate reverses drug resistance [6,7], in- creases glucose metabolism [8] and influences the activ- ity of several enzymes, either inhibiting or stimulating [9–11]. Recent data associated vanadium essentially to the treatment of diabetes, due to its insulin mimetic properties [12–14] and to the prevention of animal car- cinogens [15,16], however some studies of DÕCruz and its collaborators have reported spermicidal and anti- HIV activity of vanadium compounds [17]. Despite its toxicity at higher concentrations, vana- dium is assumed to be an essential element for organ- isms [18,19], although its biological role is far from a clear identification. In cells, oxovanadium(IV) species are essentially the vanadium species present, even though some of the interest in vanadium metallobio- chemistry is probably due to the similarities between the phosphate and vanadate chemistries in solution. In that sense, a good number of the biochemical impor- tance of vanadium is associated with the +5 oxidation state (vanadate) [9]. However, in vanadium (+5) solu- tions different oligomeric (n = 1–10) vanadate anionic species can occur simultaneously in equilibrium such 0162-0134/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.jinorgbio.2005.02.024 * Corresponding author. Tel.: +351 289 800900; fax: +351 289 819403. E-mail address: maalves@ualg.pt (M. Aureliano). www.elsevier.com/locate/jinorgbio Journal of Inorganic Biochemistry 99 (2005) 979–985 JOURNAL OF Inorganic Biochemistry