A Non-Toxic Binuclear Vanadium(IV) Complex as Insulin Adjuvant Improves the Glycemic Control in Streptozotocin-Induced Diabetic Rats

Abstract

Diabetes mellitus (DM) complications are a burden to health care systems due to the associated consequences of poor glycemic control and the side effects of insulin therapy. Recently. adjuvant therapies, such as vanadium compounds, have gained attention due to their potential to improve glucose homeostasis in patients with diabetes. In order to determine the anti-diabetic and antioxidant effects of the oxidovanadium(IV) complex (Et₃NH)₂[{VO(OH}₂)(ox)₂(µ-ox)] or Vox2), rats with streptozotocin (STZ)-induced diabetes were treated with 30 and 100 mg/kg of Vox2, orally administered for 12 days. Vox2 at 100 mg/kg in association with insulin caused a 3.4 times decrease in blood glucose in STZ rats (424 mg/dL), reaching concentrations similar to those in the normoglycemic animals (126 mg/dL). Compared to insulin alone, the association with Vox2 caused an additional decrease in blood glucose of 39% and 65% at 30 and 100 mg/kg, respectively, and an increased pancreatic GSH levels 2.5 times. Vox2 alone did not cause gastrointestinal discomfort, diarrhea, and hepatic or renal toxicity and was not associated with changes in blood glucose level, lipid profile, or kidney or liver function. Our results highlight the potential of Vox2 in association with insulin in treating diabetes.

Keywords: STZ-induced diabetic rats; adjunctive to insulin therapies; oxidovanadium(IV); treatment efficacy; vanadium.

Figure 1

Ball and stick representation of the (Et₃NH)₂[{VO(OH}₂)(ox)₂(µ–ox)], or Vox2, complex. The Vox2 structure consists of an anionic binuclear complex formulated as [V(O)(OH₂)(ox)₂(μ-ox)]²⁻, with two triethylammonium (Et3NH) as counter ions. A bis-bidentate oxalate ligand bridges the two six-coordinate vanadium centers, and the coordination sphere of each metal ion is completed by three terminal ligands: one bidentate oxalate (ox²⁻), one water molecule, and an oxide group (O²⁻). Molecular mass = 638.37 g mol⁻¹.

Figure 2

Open-Field Test after Vox2 administration.

Figure 3

Effect of Vox2 on blood glucose concentration in the different experimental stages. Values are mean ± SD (mg/dL) on first (A) and last (D) days of treatment. Blood glucose % (B) at 0, 30, 60, 120, and 180 min after treatment was initiated, assuming 100% of the concentration at time zero (0), collected immediately before the start of treatment. Mean glycemia measurement during the study period (C). Groups are NG (n = 10), normoglycemic and non-diabetic control group; Group DM (n = 6), diabetes mellitus group, STZ-induced diabetic rats untreated; Group INS (n = 6), induced diabetic rats treated with insulin; Group V₃₀ (n = 6), induced diabetic rats treated with 30 mg/kg of Vox2; Group V₁₀₀ (n = 6), induced diabetic rats treated with 100 mg/kg of Vox2, Group V_30INS (n = 6), induced diabetic rats treated with insulin plus 30 mg/kg of Vox2 and Group V_100INS (n = 6), induced diabetic rats treated with insulin plus 100 mg/kg of Vox2. The dotted line corresponds to a glucose concentration of 250 mg/dL, which is an established criterion for diabetes. In (A), all groups are not different except for the control group (NG), which is smaller than the others (**, p < 0.001). In (C), groups DM, V₃₀, and V₁₀₀ were not different. Groups NG, V_30INS, and V_100INS were not different. Statistical analysis was performed using a one-way ANOVA followed by Tukey’s test.