IMPROVEMENT IN CARDIAC DYSFUNCTION IN STREPTOZOTOCIN-INDUCED DIABETICRATS FOLLOWING CHRONIC ORAL-ADMINISTRATION OF BIS(MALTOLATO)OXOVANADIUM(IV)

Decreased cardiac function in streptozotocin-diabetic rats has been us ed as a model of diabetes-induced cardiomyopathy, which is a secondary complication in diabetic patients. The present study was designed to evaluate the therapeutic effect of a new organic vanadium complex, bis (maltolato)oxovanadium(IV), (BMOV), in improving heart function in str eptozotocin-diabetic rats. There were four groups of male, Wistar rats : control (C), control treated (CT), diabetic (D), and diabetic treate d (DT). Treatment consisted of BMOV, 0.5 mg/mL (1.8 mM) for the first 3 weeks arid 0.75 mg/mL (2.4 mM) for the next 22 weeks, in the drinkin g water of rats allowed ad libitum access to food and water. BMOV lowe red blood glucose to < 9 mM in 70% of DT animals without any increase in plasma insulin levels, and mean blood glucose and plasma lipid leve ls were significantly lower in DT vs. D rats. Tissue vanadium levels w ere measured in plasma, bone, kidney, liver, muscle, and fat of BMOV-t reated rats. Plasma vanadium levels averaged 0.84 +/- 0.07 mug/mL (16. 8 muM) in CT rats and 0.76 +/-0.05 mug/mL (15.2 muM) in DT animals. Th e highest vanadium levels at termination of this chronic feeding study were in bone, 18.3 +/- 3.0 mug/g (0.37 mumol/g) in CT and 26.4 +/- 2. 6 mug/g (0.53 mumol/g) in DT rats, with intermediate levels in kidney and liver, and low, but detectable levels in muscle and fat. There wer e no deaths in either the CT or DT group, and no overt signs of vanadi um toxicity were present. Tissue vanadium levels were not correlated w ith die glucose-lowering effect. Isolated working heart parameters of left ventricular developed pressure (LVDP) and rate of pressure develo pment (+dP/dT, and -dP/dT) indicated that BMOV treatment resulted in s ignificant correction of the heart dysfunction associated with strepto zotocin-induced diabetes in rat.