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[VIII(dipic-Cl)2] · 5H2O (V3dipic-Cl), VIVO(dipic-Cl)(H2O)2 (V4dipic-Cl) and K[VVO2(dipic-Cl)] (V5dipic-Cl), were prepared with the indicated oxidation states. Our aim was to evaluate the anti-diabetic effects of V3dipic-Cl, V4dipic-Cl and V5dipic-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 V4dipic-Cl and V5dipic-Cl complexes for the following 20 days. Although administration of both V4dipic-Cl and V5dipic-Cl significantly lowered diabetic hyperglycemia, the vanadium intake from administration of V4dipic-Cl is nearly 1.5-fold greater compared to that of V5dipic-Cl. Treatment with the H2dipic-Cl ligand and all three V-dipic-Cl complexes significantly lowered serum cholesterol, while administration of the V5dipic-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 V4dipic-Cl and V5dipic-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 H2dipic-Cl ligand and V4dipic-Cl and V5dipicCl 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 H2dipic-Cl, V3dipic-Cl, V4dipic-Cl and V5dipic-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.
Li
Ming
M
College of Life Sciences, Graduate University of Chinese Academy of Sciences, No. 19A YuQuan Road, 100049 Beijing, China.
Ding
Wenjun
W
Smee
Jason J
JJ
Baruah
Bharat
B
Willsky
Gail R
GR
Crans
Debbie C
DC
D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects*; D001806:Blood Urea Nitrogen; D002713:Chlorine / Q000737:chemistry; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000138:chemical synthesis / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007677:Kidney Function Tests; D010084:Oxidation-Reduction; D010848:Picolinic Acids / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000633:toxicity; D014280:Triglycerides / Q000097:blood; D014638:Vanadates / Q000008:administration & dosage / Q000097:blood / Q000138:chemical synthesis / Q000627:therapeutic use*; D014639:Vanadium / Q000737:chemistry
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010848:Picolinic Acids; D014280:Triglycerides; D014639:Vanadium; D014638:Vanadates; D002713:Chlorine; D013311:Streptozocin; D002784:Cholesterol; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase; C004860:dipicolinic acid