Toxic effects of vanadium in streptozotocin-treated rats after administration of vanadate to normalize blood glucose levels

Diabetologia, Jan 1990

J. L. Domingo, B. Portha

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Toxic effects of vanadium in streptozotocin-treated rats after administration of vanadate to normalize blood glucose levels

Diabetologia 0 Yours sincerely , B. Portha and O. Blondel 1 Dr. J. L. Domingo Laboratory of Toxicology and Biochemistry School of Medicine San Lorenzo 21 E-43201 Reus Spain 2 Yours sincerely , J. L: Domingo, J. M. Llobet and J. Corbella Toxic effects o f v a n a d i u m in s t r e p t o z o t o c i n - t r e a t e d rats after administration o f vanadate to n o r m a l i z e b l o o d g l u c o s e levels Dear Sir, Recently O. Blondel et al. reported an insulinqike effect of vanadate upon glucose metabolism in vivo in the liver and peripheral tissues of streptozotocin-diabetic rats, leading to normalization of glycaemia in the absence of any significant improvement of insulin secretion [1]. T h e efficacy of oral administration of vanadate in normalizing blood glucose levels of streptozotocin-treated (ST) rats was previously investigated by other authors [2, 3]. In all cases vanadate was effective in normalizing blood glucose levels. However, it was administered in drinking water at concentrations ranging between 200 and 800 parts per million (ppm), which are potentially toxic. Although Meyerovitch et al. [3] did not find signs of toxicity on the renal or hepatic function after oral vanadate treatment, other authors have reported increased levels of vanadium in several tissues after orthovanadate (50 ppm V) or sodium metavanadate (50 ppm NaV03) administration [4, 5]. Signs of renal toxicity w e r e also observed at 50 ppm NaV03 [5]. Moreover, ammonium metavanadate decreased erythropoiesis and maturation of erythrocytes when given to rats in drinking water for a period of 2, 4 or 8 weeks [6]. - R e f e r e n c e s 9 Springer-Verlag 1990 6. Zaporowska H, Wasilewski W (1989) Some selected peripheral blood and haemopoietic system indices in Wistar rats with chronic vanadium intoxication. Comp Biochem Physiol 93C: 175-180 7. Domingo JL, Llobet JM, Tomas JM, Corbella J (1986) Influence of chelating agents on the toxicity, distribution and excretion of vanadium in mice. J Appl Toxicol 6:337-341 R e s p o n s e f r o m the authors Dear Sir, The argumentation presented by Dr. Domingo et al. seems to infer that in our presentation of the data related to the vanadatetreated diabetic rats [ 1 ], we have eliminated the possibility of a toxic effect of oral vanadate. We would like to emphasize that such an assumption does not correspond to the aim of our paper. In fact, over the duration of our experimental protocol we have clearly identified in both non-diabetic and diabetic rats (Results section and Table 1) the possibilities: (1) that the treated rats did not drink at satiety at least at the begining of the oral treatments; this point has also been mentionned by Brichard et al. [ 2 ] using the same dose protocol and these authors have suggested that it may explain the presence of a marginal dehydration since the haematocrit values and serum urea a r e slightly elevated [ 2 ]; (2) that the treated rats had a slower weight gain in relationship to a decrease in food intake, thus suggesting an anorexic effect ofvanadate; this point has also been observed by Brichard et al. [ 2 ]. Nevertheless, Brichard et al. have reported that oral vanadate over a 9-week period of administration did not impair the kidney and liver functions of the rats as assessed by measurements of serum concentrations of creatinine and transaminases [ 2 ]. In a more general point of view it is considered [ 3 ] that the toxicity of vanadium is high when given by injection, low by oral route and intermediate by the respiratory tract and it seems to be established that vanadate is not very toxic in humans when given orally [ 3 ]. Finally, we stress the point that the information supplied by our work is not aimed at justifying the use of vanadate salts as a therapeutic agent; but rather they clearly identify vanadate as an interesting tool to further characterize the impairment of glucose homeostasis in diabetes and more specifically the question of insulin resistance [ 4 ]. Prof. B. Portha Universit6 Paris VII Laboratoire de Physiologie du Ddveloppement 2 Place Jussieu F-75251 Paris Cedex 05 France Diabetes and Exercise '90 This international scientific symposium will be held in Dtisseldorf from May 19-21, 1990. Co-sponsored by The World Health Organisation, European Association for the Study of Diabetes and the German Diabetes Association. Organising Committee: M.Berger (FRG), E. S. Horton (USA), N. B. Ruderman (USA), E W.Kemmer (FRG). Participation limited to 100 colleagues, including a faculty of approximately 25 experts. The submission of abstracts (up to 500 words) for short communications and posters is encouraged; deadline March 1, 1990. Address for information and submission of abstracts:Dr. M. Berger, Professor of Medicine, Department of Medicine E, Moorenstrasse 5, D-4000 Dtisseldorf, FRG. 1. Blondel O , Bailbe D , Portha B ( 1989 ) In vivo insulin resistance in streptozotocin-diabeticrats - evidence for reversal following oral vanadate treatment . Diabetologia 32 : 185 - 190 2. Brichard S , Okitolonda W , Henquin JC ( 1988 ) Long term improvement of glucose homeostasis by vanadate treatment in diabetic rats . Endocrinology 123 : 2048 - 2053 3. Nechay BR , Nanninga LB , Nechay PSE , Post RL , Grantham JJ , Macara IG , Kubena LF , Phillips TO , Nielsen FH ( 1986 ) Role of vanadium in biology . Fed Proc 45 : 123 - 132 4. Blondel O , Chevalier B , Simon J , Portha B ( 1989 ) Impaired insulin action but normal insulin receptor activity in the liver of neonatal (5 days) streptozotocin diabetic rats. Effect of oral vanadate treatment . Diabetologia 32 : 467 (Abstract) A n n o u n c e m e n t

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J. L. Domingo, B. Portha. Toxic effects of vanadium in streptozotocin-treated rats after administration of vanadate to normalize blood glucose levels, Diabetologia, 1990, 62-63, DOI: 10.1007/BF00586463