Effects of three and eight weeks oral administration of bis(maltolato)oxovanadium(IV) on plasma homocysteine and cysteine levels in streptozotocin-induced diabetic rats.
BACKGROUND
Diabetes mellitus is one of the leading causes of illness and death in North America. Cardiovascular diseases are a common secondary complication in the diabetic population. One of the important risk factors identified for the development of cardiovascular disease is an elevation in the sulfur amino acid, homocysteine. Although the exact mechanism(s) that underlie the relationship between elevated plasma homocysteine levels and cardiovascular disease remain unclear, it has been suggested that endothelial dysfunction produced by modestly elevated blood homocysteine concentrations may account for an increased risk of both arterial and venous occlusive disease.


OBJECTIVE
The present study examined the effects of three- and eight-weeks bis(maltolato)oxovanadium(IV) (BMOV) treatment on plasma concentrations of homocysteine and cysteine in both control and streptozotocin (STZ) diabetic rats.


METHODS
Diabetes was induced in male Wistar rats by a single intravenous injection of STZ (60 mg/kg) in normal saline. Control animals received normal saline only. Animals were further randomized into treated and untreated groups. Treated animals received BMOV orally, dissolved in tap water, while untreated animals only received tap water. Three or eight weeks postinduction of diabetes, blood samples were obtained by cardiac puncture from the animals. Plasma harvested from each blood sample was used to determine glucose, insulin, homocysteine and cysteine concentrations.


RESULTS
There was a significant decrease in plasma homocysteine levels in the diabetic (three- and eight-week study) groups compared with their respective controls (three-week study: diabetic group 3.1+/-0.7 mumol/L and control group 6.1+/-0.7 mumol/L; eight-week study: diabetic group 4.3+/-0.5 mumol/L and control group 6.9+/-1.0 mumol/L). Plasma cysteine levels were significantly decreased in the diabetic and diabetic treated groups (eight-week study) compared with their respective control groups (diabetic group 90.2+/-32.3 mumol/L and control group 177.9+/-36.7 mumol/L). BMOV treatment restored plasma homocysteine concentrations in diabetic animals to concentrations found in nondiabetic animals.


CONCLUSIONS
Taken together, these findings suggest that STZ-induced diabetes may result in decreased plasma homocysteine and cysteine levels and that BMOV treatment may increase plasma homocysteine concentrations to nondiabetic concentrations. These results may provide further insight on how this insulin-enhancing/mimetic agent modifies plasma homocysteine metabolism.
Wasan
Kishor M
KM
Faculty of Pharmaceutical Sciences, Division of Pharmaceutics and Biopharmaceutics and.
Risovic
Verica
V
Yuen
Violet G
VG
Hicke
Alan
A
McNeill
John H
JH