Abstract:

Vanadium compounds are promising anti-diabetic agents. However, the concern in the toxicity, especially the long-term renal side effect along with diabetic status, is restricting the further development of this metal drug. Recently, we have prepared a bis((5-hydroxy-4-oxo-4H-pyran-2-yl) methyl 2-hydroxy-benzoatato) oxovanadium (BSOV), which exhibited excellent hypoglycemic effect with low acute toxicity. In order to facilitate the development of anti-diabetic vanadium complexes, especially BSOV, we studied the long-term toxicity and hypoglycemic effect of BSOV in comparison with bis(maltolato)oxovanadium (BMOV) on both non-diabetic and type II diabetic mice. The experiments confirmed a stable hypoglycemic effect for both the vanadium complexes over the testing period (6–7 months). However, the chronic administration of vanadium compounds slightly increased oxidative stress in ICR mice and the induced renal interstitial edema (RIE) in a part of the diabetic animals associated with low levels of serum albumin. The use of an antioxidant dietary supplement (a combination of vitamin C and Zinc gluconate) could prevent vanadium-induced oxidative stress but have marginal effect on RIE. However, BSOV caused much lower incidence of RIE than BMOV did, suggesting that BSOV is an important step towards the successful development of anti-diabetic vanadium drugs.

Key words: Bis((5-hydroxy-4-oxo-4H-pyran-2-yl) methyl 2-hydroxy-benzoatato) oxovanadium, Vanadium, Diabetes, Long-term toxicity