Abstract

The kinetics of the decomposition of 0.5 and 1.0 mM sodium decavanadate (NaDeca) and metforminium decavanadate (MetfDeca) solutions were studied by 51V NMR in Dulbecco’s modified Eagle’s medium (DMEM) medium (pH 7.4) at 25 °C. The results showed that decomposition products are orthovanadate [H2VO4]− (V1) and metavanadate species like [H2V2O7]2− (V2), [V4O12]4− (V4) and [V5O15]5− (V5) for both compounds. The calculated half-life times of the decomposition reaction were 9 and 11 h for NaDeca and MetfDeca, respectively, at 1 mM concentration. The hydrolysis products that presented the highest rate constants were V1 and V4 for both compounds. Cytotoxic activity studies using non-tumorigenic HEK293 cell line and human liver cancer HEPG2 cells showed that decavanadates compounds exhibit selectivity action toward HEPG2 cells after 24 h. The effect of vanadium compounds (8–30 μM concentration) on the protein expression of AKT and AMPK were investigated in HEPG2 cell lines, showing that NaDeca and MetfDeca compounds exhibit a dose-dependence increase in phosphorylated AKT. Additionally, NaDeca at 30 µM concentration stimulated the glucose cell uptake moderately (62%) in 3T3-L1 adipocytes. Finally, an insulin release assay in βTC-6 cells (30 µM concentration) showed that sodium orthovanadate (MetV) and MetfDeca enhanced insulin release by 0.7 and 1-fold, respectively.

Highlights

  • Polyoxometalates (POMs) have several applications in biology and medicine

  • The 51 V NMR spectra for 1 mM concentration of NaDeca and MetfDeca compounds were recorded at pH 4 in 10% DMSO-d6 and 90% H2 O (v/v), showing three signals at −420, −494, −510 ppm that were assigned to decameric species [V10 O28 ]6− (V10 ), attributed to the three different vanadium atoms of the Inorganics 2020, 8, x FOR PEER REVIEW

  • The V NMR spectra for 1 mM concentration of NaDeca and MetfDeca compounds were4 of 20 recorded at pH 4 in 10% DMSO-d6 and 90% H2O (v/v), showing three signals at −420, −494, −510 ppm that were assigned to decameric species [V10O28]6− (V10), attributed to the three different vanadium decavanadate structure V10A, V10B and V10C respectively and one signal at −556 ppm assigned to the atoms of the decavanadate structure V−

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Summary

Introduction

Polyoxometalates (POMs) have several applications in biology and medicine. Interactions between the highly charged POM molecules and biological molecules frequently occur through hydrogen-bonding and electrostatic interactions [1]. POMs have shown pharmacological activities in vitro and in vivo, such as antitumor, antimicrobial, and antidiabetic [2,3] Their roles in biological systems are non-functional or functional kind of interactions with biomolecules [4], like the tungstate cluster that helps to solve the X-ray structure of ribosome [5] or the insulin-like properties of the decavanadates [6]. The decavanadate decomposition rate is faster in acid than present in decavanadate solutions at neutral pH [15]. The decavanadate decomposition rate is faster in basic solutions [16,17] In the latter, the reaction proceeds via base-dependent or base-independent in acid than in basic solutions [16,17]. Paths,on and it depends on the counterions in the solution [17]

Schematic structure decavanadate anion
Characterization of the Sodium and Metforminium Decavanadate Solutions
Kinetic Studies by 51 V NMR
51 V NMR Signal a Decavanadate
Proteins Expression
Glucose Uptake Assay
Effect of vanadium compounds in 3T3-L1
Insulin Release Assay effect on insulin release
VO4 atoocytes channels expressed
Chemicals and Reagents
Kinetic Studies
Cell Viability Assay
Western Blot Analysis
Adipocyte Differentiation
Insulin Release Assay
Statistical Analysis
Conclusions
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