In Vitro, Oral Acute, and Repeated 28-Day Oral Dose Toxicity of a Mixed-Valence Polyoxovanadate Cluster

Abstract

Polyoxovanadates (POV) are a subgroup of polyoxometalates (POM), which are nanosized clusters with reported biological activities. This manuscript describes the first toxicity evaluation of a mixed-valence polyoxovanadate, pentadecavanadate, (Me4N)6[V15O36Cl], abbreviated as V15. Cytotoxicity experiments using peripheral blood mononuclear cells (PBMC), larvae of Artemia salina Leach, and in vivo oral acute and repeated 28-day doses in mice was carried out. The LC50 values in PBMC cells and A. salina were 17.5 ± 5.8 μmol L−1, and 17.9 µg L−1, respectively, which indicates high cytotoxic activity. The toxicity in mice was not observed upon acute exposure in a single dose, however, the V15 repeated 28-day oral administration demonstrated high toxicity using 25 mg/kg, 50 mg/kg and, 300 mg/kg doses. The biochemical and hematological analyses during the 28-day administration of V15 showed significant alteration of the metabolic parameters related to the kidney and liver, suggesting moderate toxicity. The V15 toxicity was attributed to the oxidative stress and lipid peroxidation, once thiobarbituric acid (TBAR) levels significantly increased in both males and females treated with high doses of the POV and also in males treated with a lower dose of the POV. This is the first study reporting a treatment-related mortality in animals acutely administrated with a mixed-valence POV, contrasting with the well-known, less toxic decavanadate. These results document the toxicity of this mixed-valence POV, which may not be suitable for biomedical applications.

Dexamethasone-Induced Insulin Resistance Attenuation by Oral Sulfur–Oxidovanadium(IV) Complex Treatment in Mice

“…The electronic absorption spectroscopy of the 2.0 mmol L −1 aqueous solution of the [V IV O(octd)] complex showed a broad band that extended from 600 nm to the near-infrared (maximum in 996 nm) assigned to an intervalence charge transfer transition (IVCT, V IV → V V ) characteristic of a mixture of the V IV and V V complexes, partly [V IV O(octd)] in the reduced form and partly in the oxidized form [V V O 2 (octd)]. This hypothesis was supported by the 51 V NMR and EPR tests [27]; after 1 h, the V(IV) compound was oxidized to the V V species, which was consistent with the decrease in absorbance observed in the absorption spectrum over time (Figure 1).…”

“…Some vanadium-based compounds exacerbate allergic airway inflammation by triggering reactive oxidative stress [ 50 ]. Polyoxovanadate, for example, induces severe toxicity in mice, at least in part by increasing oxidative stress, as seen in both an elevation of MDA levels and a reduction in the GSH/GSSG ratio [ 51 ]. The design of different ligands in the coordination sphere of vanadium-based complexes has allowed for more bioactive compound building (antioxidant, hepato-protective, and antidiabetic) with reduced side effects.…”

“…The FTIR spectrum of the solid contains characteristic bands of the oxidovanadium complex at 961, 615, and 530 cm −1 assigned to ν(V=O), ν(C-S), and ν(V-O) stretching, respectively. Additionally, a time-dependent decomposition study of [V IV O(octd)] in an aqueous solution was realized using 51 V NMR, EPR, and electronic absorption spectroscopy, thus enabling the monitoring of vanadium(V) species formation [27]. The EPR spectrum of [V IV O(octd)] in DMSO displayed an eight-line pattern (Figure S1, Supplementary Materials), consistent with the vanadium nuclear hyperfine couplings of oxidovanadium(IV) complexes ( 51 V, I = 7/2) and like V IV OSO 4 , which is used as standard.…”

“…The 51 V NMR of a 2.0 mmol L −1 aqueous solution of [V IV O(octd)], pH~4, showed a signal at -557 ppm assigned to a monomer V 1 (H 2 VO 4 -). Over time, after 72 h, the 51 V NMR showed signals (-424, -504, and -522 ppm) assigned to the oligomer decavanadate V 10 (V 10 O 28 6− ) (Figure S2, Supplementary Materials). The electronic absorption spectroscopy of the 2.0 mmol L −1 aqueous solution of the [V IV O(octd)] complex showed a broad band that extended from 600 nm to the near-infrared (maximum in 996 nm) assigned to an intervalence charge transfer transition (IVCT, V IV → V V ) characteristic of a mixture of the V IV and V V complexes, partly [V IV O(octd)] in the reduced form and partly in the oxidized form [V V O 2 (octd)].…”

“…The 51 V NMR of a 2.0 mmol L −1 aqueous solution of [V IV O(octd)], pH~4, showed a signal at -557 ppm assigned to a monomer V1 (H2VO4 -). Over time, after 72 h, the 51 V NMR showed signals (-424, -504, and -522 ppm) assigned to the oligomer decavanadate V10 (V10O28 6− ) (Figure S2, Supplementary Materials).…”