Improvement in cardiac dysfunction in streptozotocin-induced diabetic rats following chronic oral administration of bis(maltolato)oxovanadium(IV).
Decreased cardiac function in streptozotocin-diabetic rats has been used 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 streptozotocin-diabetic rats. There were four groups of male, Wistar rats: control (C), control treated (CT), diabetic (D), and diabetic treated (DT). Treatment consisted of BMOV, 0.5 mg/mL (1.8 mM) for the first 3 weeks and 0.75 mg/mL (2.4 mM) for the next 22 weeks, in the drinking water of rats allowed ad libitum access to food and water. BMOV lowered blood glucose to < 9 mM in 70% of DT animals without any increase in plasma insulin levels, and mean blood glucose and plasma lipid levels were significantly lower in DT vs. D rats. Tissue vanadium levels were measured in plasma, bone, kidney, liver, muscle, and fat of BMOV-treated rats. Plasma vanadium levels averaged 0.84 +/- 0.07 microgram/mL (16.8 microM) in CT rats and 0.76 +/- 0.05 microgram/mL (15.2 microM) in DT animals. The highest vanadium levels at termination of this chronic feeding study were in bone, 18.3 +/- 3.0 micrograms/g (0.37 mumol/g) in CT and 26.4 +/- 2.6 micrograms/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 were no deaths in either the CT or DT group, and no overt signs of vanadium toxicity were present. Tissue vanadium levels were not correlated with the glucose-lowering effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Yuen
V G
VG
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Orvig
C
C
Thompson
K H
KH
McNeill
J H
JH
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy / Q000209:etiology; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006331:Heart Diseases / Q000188:drug therapy* / Q000209:etiology*; D006943:Hyperglycemia / Q000188:drug therapy / Q000209:etiology; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D011753:Pyrones / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014018:Tissue Distribution; D014280:Triglycerides / Q000097:blood; D014638:Vanadates / Q000494:pharmacology* / Q000633:toxicity; D014639:Vanadium / Q000378:metabolism / Q000493:pharmacokinetics
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D011753:Pyrones; D014280:Triglycerides; D014639:Vanadium; C074212:bis(maltolato)oxovanadium(IV); D014638:Vanadates; D002784:Cholesterol