Vanadate Induces Necrotic Death in Neonatal Rat Cardiomyocytes Through Mitochondrial Membrane Depolarization

Abstract

Besides the well-known inotropic effects of vanadium in cardiac muscle, previous studies have shown that vanadate can stimulate cell growth or induce cell death. In this work, we studied the toxicity to neonatal rat ventricular myocytes (cardiomyocytes) of two vanadate solutions containing different oligovanadates distribution, decavanadate (containing decameric vanadate, V 10) and metavanadate (containing monomeric vanadate and also di-, tetra-, and pentavanadate). Incubation for 24 h with decavanadate or metavanadate induced necrotic cell death of cardiomyocytes, without significant caspase-3 activation. Only 10 microM total vanadium of either decavanadate (1 microM V 10) or metavanadate (10 microM total vanadium) was needed to produce 50% loss of cell viability after 24 h (assessed with MTT and propidium iodide assays). Atomic absorption spectroscopy showed that vanadium accumulation in cardiomyocytes after 24 h was the same when incubation was done with decavanadate or metavanadate. A decrease of 75% of the rate of mitochondrial superoxide anion generation, monitored with dihydroethidium, and a sustained rise of cytosolic calcium (monitored with Fura-2-loaded cardiomyocytes) was observed after 24 h of incubation of cardiomyocytes with decavanadate or metavanadate concentrations close to those inducing 50% loss of cell viability produced. In addition, mitochondrial membrane depolarization within cardiomyocytes, monitored with tetramethylrhodamine ethyl esther or with 3,3',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide, were observed after only 6 h of incubation with decavanadate or metavanadate. The concentration needed for 50% mitochondrial depolarization was 6.5 +/- 1 microM total vanadium for both decavanadate (0.65 microM V 10) and metavanadate. In conclusion, mitochondrial membrane depolarization was an early event in decavanadate- and monovanadate-induced necrotic cell death of cardiomyocytes.

Biocompatible Bright YVO4:Eu Nanoparticles as Versatile Optical Bioprobes

“…The toxicology of Y 3 + and Eu 3 + is still undeveloped, while some research has reported that Ln has similar physiological functions to calcium. [ 27 ] According to bioinorganic chemistry studies of vanadium, [ 28 ] the leakage quantity of VO 4 3 − from the Ln NPs would not exhibit significant toxicity, [ 29 ] which confi rms our MTT assay. Based on the above evidence, the Ln NPs prove to possess a considerable biocompatibility.…”

Sarcoplasmic Reticulum Calcium ATPase Is Inhibited by Organic Vanadium Coordination Compounds: Pyridine-2,6-dicarboxylatodioxovanadium(V), BMOV, and an Amavadine Analogue

“…11,[55][56][57] The calcium pump has previously been found to be inhibited by the vanadium citrate complex; 25 however, the studies shown here demonstrate more potent interactions with the PDC-V(V) and BMOV systems. Recent studies demonstrated that the redox properties of the vanadium complexes are important to their insulin-enhancing action.…”

Cyto- and genotoxicity of a vanadyl(IV) complex with oxodiacetate in human colon adenocarcinoma (Caco-2) cells: potential use in cancer therapy

“…12 Comparison of cleavage activity of VO(oda) with other vanadium nucleases: VO(acac) 2 , VO(hd) 2 and VO(Et-acac) 2 Costa Pessoa et al 2007;Cavaco et al 2009). Cleavage efficiency is measured by the slope of the straight line of the logarithm of the percentage of Sc (log SC) with complex concentration tumorigenic and non carcinogenic cells , as well as the toxicity of vanadate solution in cardiomyocytes (Soares et al 2008). Moreover, it has been also previously reported that vanadocenes blocked the cell division in human cancer cells by disrupting bipolar spindle formation.…”