College of Life Sciences, Graduate University of Chinese Academy of Sciences, No. 19A YuQuan Road, 100049 Beijing, China.
Biometals. 2009 Dec;22(6):895-905. doi: 10.1007/s10534-009-9241-4.
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.
钒(III、IV、V)-氯代二吡啶酸（二吡啶-Cl）配合物，包括 H[VIII（二吡啶-Cl）2]·5H2O（V3dipic-Cl）、VIVO（二吡啶-Cl）（H2O）2（V4dipic-Cl）和 K[VVO2（二吡啶-Cl）]（V5dipic-Cl），均以指定的氧化态制备。我们的目的是评估 V3dipic-Cl、V4dipic-Cl 和 V5dipic-Cl 在链脲佐菌素诱导的糖尿病大鼠中的抗糖尿病作用。将钒配合物以 0.1-0.3mg/ml 的浓度在饮用水中口服给予糖尿病大鼠。我们发现，当以 0.1mg/ml 的浓度给予糖尿病大鼠 20 天时，钒-氯代二吡啶酸（V-dipic-Cl）配合物没有降低血糖的作用。然而，在用 0.3mg/ml 的 V4dipic-Cl 和 V5dipic-Cl 配合物治疗 20 天后，糖尿病大鼠的空腹血糖水平降低。尽管 V4dipic-Cl 和 V5dipic-Cl 两者的给药均显著降低了糖尿病性高血糖，但从 V4dipic-Cl 给药中摄取的钒几乎是 V5dipic-Cl 的 1.5 倍。H2dipic-Cl 配体和三种 V-dipic-Cl 配合物的治疗均显著降低了血清胆固醇，而 V5dipic-Cl 配合物的给药显著降低了血清胆固醇，而单独给药则没有效果。单独给予配体对血清三酰甘油没有影响，而 V4dipic-Cl 和 V5dipic-Cl 的给药则显著降低了糖尿病引起的升高的血清三酰甘油。配体和所有 V-dipic-Cl 配合物的口服给药均显著降低了糖尿病升高的血清碱性磷酸酶。用 H2dipic-Cl 配体和 V4dipic-Cl 和 V5dipicCl 治疗显著降低了糖尿病升高的天门冬氨酸氨基转移酶。这些结果表明，与糖尿病动物相比，治疗动物的健康状况似乎没有进一步恶化。此外，在 0.3mg/ml 的剂量下，H2dipic-Cl、V3dipic-Cl、V4dipic-Cl 和 V5dipic-Cl 的口服给药并未改变糖尿病大鼠的血清肌酐和血尿素氮水平，表明钒治疗对肾功能没有明显的副作用。这里呈现的结果表明，用 V-dipic-Cl 配合物治疗的抗糖尿病作用可能部分与钒的氧化态有关。
