Anti-diabetic effects of vanadium(III, IV, V)-chlorodipicolinate complexes in streptozotocin-induced diabetic rats

Vanadium(III, IV, V)-chlorodipicolinate (dipic-Cl) complexes, including H[V-III(dipic-Cl)(2)] center dot A 5H(2)O (V(3)dipic-Cl), (VO)-O-IV(dipic-Cl)(H2O)(2) (V(4)dipic-Cl) and K[(VO2)-O-V(dipic-Cl)] (V(5)dipic-Cl), were prepared with the indicated oxidation states. Our aim was to evaluate the anti-diabetic effects of V(3)dipic-Cl, V(4)dipic-Cl and V(5)dipic-Cl in streptozotocin-induced diabetic rats. Vanadium complexes were orally administered to diabetic rats at concentrations of 0.1-0.3 mg/ml in the drinking water. We found that vanadium-chlorodipicolinate (V-dipic-Cl) complexes at the concentration of 0.1 mg/ml did not exhibit blood glucose-lowering effects when administered to diabetic rats for 20 days. However, the levels of fasting blood glucose in diabetic rats were decreased after treatment with 0.3 mg/ml of V(4)dipic-Cl and V(5)dipic-Cl complexes for the following 20 days. Although administration of both V(4)dipic-Cl and V(5)dipic-Cl significantly lowered diabetic hyperglycemia, the vanadium intake from administration of V(4)dipic-Cl is nearly 1.5-fold greater compared to that of V(5)dipic-Cl. Treatment with the H(2)dipic-Cl ligand and all three V-dipic-Cl complexes significantly lowered serum cholesterol, while administration of the V(5)dipic-Cl complex lowered serum cholesterol significantly more than administration of the ligand alone. Treatment with ligand alone did not have an effect on serum triglyceride, while administration of the V(4)dipic-Cl and V(5)dipic-Cl significantly lowered the elevated serum triglyceride associated with diabetes. Oral administration of the ligand and all V-dipic-Cl complexes did significantly lower diabetes elevated serum alkaline phosphatase. Treatment with H(2)dipic-Cl ligand and V(4)dipic-Cl and V(5)dipicCl significantly lowered diabetes elevated aspartate amino transferase. These results indicate that the health of the treated animals did not seem to be further compromised compared to that of diabetic animals. In addition, oral administration of H(2)dipic-Cl, V(3)dipic-Cl, V(4)dipic-Cl and V(5)dipic-Cl did not alter diabetic serum creatinine and blood urea nitrogen levels, suggesting no significant side effects of vanadium treatment on renal functions at the dose of 0.3 mg/ml in diabetic rats. The results presented here suggest that the anti-diabetic effects of treatment with V-dipic-Cl complexes were likely associated in part with the oxidation state of vanadium.