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

Pharmaceuticals (Basel). 2023 Aug 30;16(9):1232. doi: 10.3390/ph16091232.

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.

Keywords: mixed valence; oral acute toxicity; pentadecavanadate; polyoxovanadates; toxicology.

Grants and funding

This research was funded by CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), grants 406946/2021-3 and 309691/2021-4 (to E.C.L.), CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Finance Code 001) (to E.C.L.), PrInt/CAPES-UFPR (Internationalization Program for scholarships and financial support) (to K.P.), FACEPE (Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco), grant AMD 0060-1.06/2019 (to E.C.L. and L.M.A.d.L), and Colorado State University (to D.C.C.).