CrossRef enabled

PAC Archives

Archive →

Pure Appl. Chem., 2005, Vol. 77, No. 9, pp. 1617-1628

Oral therapy of L-glutamic acid γ-monohydroxamate-vanadium (2:1) complex: Improvement of blood glucose profile in different types of diabetic rodents

Y. Shechter1, I. Goldwaser1,2, M. Mironchik1, H. Tsubery1,2 and M. Fridkin2

1 Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel
2 Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel

Abstract: We report that oral administration of vanadium (+5) combined with L-glutamic acid γ-monohydroxamate at 1:2 stoichiometry [L-Glu(γ)HXM.VO3-] is highly effective in reducing blood glucose levels (BGLs) in a wide variety of diabetic rodents. In streptozocin-treated rats, a single administration (0.28 mmol/kg body wt) decreased BGL from 490 to 360 mg/dl within 1 h of administration, keeping this reduced level for additional 22 h, and a daily dose of 0.14 mmol/kg was found optimal. In Zucker diabetic fatty (ZDF) rats, a single dose of 0.14 mmol/kg normalized BGL within 8 h of administration, and maintained normal value for additional two days. In db/db mice, a single L-Glu(γ)HXM.VO3- administration of 0.2 mmol/kg decreased BGL from 500 ± 50 to 240 ± 20 mg/dl at 2 h, but was less effective afterwards. In high-carbohydrate (CHO)-fed Psammomis obesus, a single oral dose (0.14 mmol/kg) normalized BGL over a period of two days, and a daily dose of 0.07 mmol/kg/d, at the time P. obesus was transferred from low- to high-CHO diet, fully arrested the development of hyperglycemia characterizing this diabetic rodent. Finally, we found that the index of toxicity of orally administered L-GLU(γ)HXM-vanadate in rodents is 5-7 times lower than that of free sodium vanadate.