Vanadium in diabetes: 100 years from Phase 0 to Phase I.

Vanadium and proteins: Uptake, transport, structure, activity and function

The possible use of vanadium compounds in the treatment of diabetic patients is now being evaluated. However, previously to establish the optimal maximum dose for diabetes therapy, it should be taken into account that vanadium is a highly toxic element to man and animals. The toxic effects of vanadium are here reviewed. The tissue vanadium accumulation, which would mean an additional risk of toxicity following prolonged vanadium administration is also discussed. Recently, it has been shown that coadministration of vanadate and TIRON, an effective chelator in the treatment of vanadium intoxication, reduced the tissue accumulation of this element, decreasing the possibility of toxic side effects derived from chronic vanadium administration without diminishing the hypoglycemic effect of vanadium. However, previously to assess the effectiveness of this treatment in diabetic patients, a critical reevaluation of the antidiabetic action of vanadium and its potential toxicity is clearly needed.

Toxicology of vanadium compounds in diabetic rats: The action of chelating agents on vanadium accumulation

Vanadyl (IV) and vanadate (V) binding to selected endogenous phosphate, carboxyl, and amino ligands; calculations of cellular vanadium species distribution.

The interaction of VIVO2+ ion with hemoglobin (Hb) was studied with the combined application of spectroscopic (EPR), spectrophotometric (UV–vis), and computational (DFT methods) techniques. Binding of Hb to VIVO2+ in vitro was proved, and three unspecific sites (named α, β, and γ) were characterized, with the probable coordination of His–N, Asp–O–, and Glu–O– donors. The value of log β for (VO)Hb is 10.4, significantly lower than for human serum apo-transferrin (hTf). In the systems with VIVO potential antidiabetic compounds, mixed species cis-VOL2(Hb) (L = maltolate (ma), 1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate (dhp)) are observed with equatorial binding of an accessible His residue, whereas no ternary complexes are observed with acetylacetonate (acac). The experiments of uptake of [VO(ma)2], [VO(dhp)2], and [VO(acac)2] by red blood cells indicate that the neutral compounds penetrate the erythrocyte membrane through passive diffusion, and percent amounts higher than 50% are found in the intracellular m...

J. Koch

Papers

Effects of vanadate on intracellular reduction equivalents in mouse liver and the fate of vanadium in plasma, erythrocytes and liver.