Toxicity studies on one-year treatment of non-diabetic and streptozotocin-diabetic rats with vanadyl sulphate.
Streptozotocin-diabetic and non-diabetic rats were given vanadyl sulphate in drinking water at concentrations of 0.5-1.5 mg/ml for one year. It was found that vanadyl treatment did not produce persistent changes in plasma aspartate aminotransferase, alanine aminotransferase, and urea, specific morphological abnormalities in the brain, thymus, heart, lung, liver, spleen, pancreas, kidney, adrenal, or testis, or abnormal organ weight/body weight ratio for these organs in either non-diabetic or diabetic animals. Treatment significantly reduced the incidence of the occurrence of urinary stones in non-diabetic rats. In diabetic animals vanadyl treatment significantly reduced the mortality rate and prevented the elevation of plasma levels of alanine aminotransferase and urea, the increases in organ size, and the occurrence of megacolon but did not affect the development of renal and testicular tumours. Plasma and tissue concentrations of vanadium were determined and found to have the following order of distribution: bone > kidney > testis > liver > pancreas > plasma > brain. Vanadium was retained in these organs at 16 weeks following vanadyl withdrawal while the plasma levels were beneath detection limits. It is concluded that vanadyl sulphate at antidiabetic doses is not significantly toxic to rats following a one-year administration in drinking water, but vanadium may be retained in various organs for months after cessation of treatment.
Dai
S
S
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Thompson
K H
KH
Vera
E
E
McNeill
J H
JH
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D014018:Tissue Distribution / Q000187:drug effects; D014508:Urea / Q000097:blood; D014545:Urinary Calculi / Q000517:prevention & control; D017968:Vanadium Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*
D017968:Vanadium Compounds; D013311:Streptozocin; C034028:vanadyl sulfate; D014508:Urea; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase