Abstract
Since it has been claimed that vanadate is an endogenous regulator of Na/K-ATPase activity and that it potentiates the toxicity of cardiac glycosides, we were alarmed to discover that certain Finnish physicians were prescribing vanadate in combination with other trace minerals to elderly patients for many different chronic diseases (e.g., cancer, rheumatism). To study the interaction of vanadate and cardiac glycosides, we fed vanadate in the drinking water (25 μg/mL) to guinea pigs for 20 d, and studied either their sensitivity to the acute toxicity of the cardiac glycoside ouabain or whether the vanadate would influence the subacute toxicity of ouabain. Vanadate had no influence on the toxicity of ouabain either acute or subchronically administered, nor was there any sign of inhibition of Na/K-ATPase activity as measured by86Rb-uptake into intact erythrocytes (RBCs), RBC content of sodium or potassium or Na/K-ATPase activity in RBC membranes prepared from the vanadate-treated guinea pigs. Vanadate had been absorbed in substantial quantities from the gastrointestinal tract, since serum, heart, liver, and especially kidney contained measurable amounts of vanadium in contrast to controls, but it is concluded that this vanadate is not in a biologically active form.
Similar content being viewed by others
References
L. C. Cantley Jr., L. Josephson, R. Warner, M. Yanagisawa, C. Lechene, and G. Guidotti,J. Biol. Chem. 252, 7421 (1979).
L. A. Beauge and I. M. Glynn,Nature 272, 551 (1978).
E. Erdmann, K. Werdan, W. Krawietz, W. Schmitz and H. Scholz,Biochem. Pharmacol. 33, 945 (1984).
B. R. Nechay,Ann. Rev. Pharmacol Toxicol. 24, 501 (1984).
T. W. Smith and E. Haber,J. Clin. Invest. 49, 2337 (1970).
D. T. Mason and J. M. Foerster, inHandbook of Experimental Pharmacology, vol. 56/I, K. Greeff, ed., Springer-Verlag, Berlin, Heidelberg, NY, 1981, pp. 275–297.
P. Puig-Parellada, J. M. Planas, F. Marmol, and F. G. Valdecasas,Pharmacol. Res. Commun. 13, 571 (1981).
H. Higashino, J. D. Bogden, M. A. Lavenhar, J. W. Bauman Jr., T. Hirotsu, and A. Aviv,Am. J. Physiol. 244, F105 (1983).
E. MacDonald and K. Hellevuo,Lancet II, 579, (1983).
O. Impivaara,Acta Med. Scand. 218, 285 (1985).
Pharmacopoeia Nordica-Editio Fennica, Vol. 4, 127 (1961).
M. De Luise, G. L. Blackburn, and J. S. Flier,New Engl J. Med. 303, 1017 (1980).
M. Reinila, E. MacDonald, N. Salem Jr., M. Linnoila, and E. G. Trams,Anal. Biochem. 124, 19 (1982).
O. Lowry, N. J. Rosebrough, A. L. Farr, and R. J. Randall,J. Biol. Chem. 193, 265 (1951).
S. D. Stroop, G. Helinek, and H. L. Greene,Clin. Chem. 28/1, 79 (1982).
H. Bahrmann and K. Greeff, inHandbook of Experimental Pharmacology, vol. 56/I, K. Greeff, ed., Springer-Verlag, Berlin, Heidelberg, NY, 1981, pp. 117–152.
I. G. Macara, K. Kustin, and L. C. Cantley,Biochim. Biophys. Acta 629, 95 (1980).
O. Hansen,Acta Pharmacol. Toxicol. 52, Supp. 1, (1983).
B. Lagerkvist, G. F. Nordberg, and V. Vouk, inHandbook in the Toxicology of Metals, L. Friberg, G. F. Nordberg, and V. B. Vouk, eds., Elsevier, Amsterdam, NY, Oxford, 1986, pp. 638–663.
T. D. Myers, R. C. Boerth, and R. L. Post,Biochim. Biophys. Acta 558, 99 (1979).
J. D. Bogden, H. Higashino, M. A. Lavenhar, J. W. Bauman Jr., F. W. Kemp, and A. Aviv,J. Nutr. 112, 2279 (1982).
A. H. L. From, G. J. Quarfoth, B. W. Steele, and K. Ahmed,Eur. J. Clin. Pharmacol. 24, 807 (1983).
J. K. Aronson, inClinical Pharmacology & Therapeutics, P. Turner, ed., Macmillan, London, Basingstoke, 1980, pp. 135–144.
D. E. Jackson,J. Pharmacol. Exp. Ther. 3, 477 (1912).
W. E. Balfour, J. C. Grantham, and I. M. Glynn,Nature 275, 768 (1978).
J. M. Lopez-Novoa, J. C. Garcia, M. A. Cruz-Sota, J. E. Benabe, and M. Martinez-Maldonado,J. Pharmacol. Exp. Ther. 222, 447 (1982).
P. C. Churchill and M. C. Churchill,J. Pharmacol. Exp. Ther. 213, 144 (1980).
L. Vivas and E. Chiaraviglio,Brain Res. Bull. 17, 469 (1985).
R. D. R. Parker and R. P. Sharma,J. Environ Path. Toxicol. 2, 235 (1978).
L. C. Cantley, Jr., M. G. Resh, and G. Giudotti,Nature 272, 552 (1978).
K. A. Rubinson,Proc. R. Soc. London Ser. B,212, 65 (1981).
H. Komulainen and J. Tuomisto,Acta Pharmacol. Toxicol. 48, 205 (1981).
H. Komulainen,Acta Pharmacol. Toxicol. 53, 33 (1983).
S. Marshall, W. T. Garvey, and R. Monzon,J. Biol. Chem. 262, 12005 (1987).
S. Kadota, I. G. Fantus, G. Deragon, H. G. Guyda, B. Hersh, and B. I. Posner,Biochem. Biophys. Res. Commun. 147, 259 (1987).
G. F. Fuhrmann, M. Bruch, and K. J. Netter,Abstracts X Int. Con. Pharmacol. S100 (1987).
R. A. Naylor and H. W. Mitchell,Br. J. Pharmacol. 92, 173 (1987).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
MacDonald, E., Lihtamo, H., Hellevuo, K. et al. Subchronic treatment with vanadate does not potentiate the toxicity of cardiac glycosides. Biol Trace Elem Res 16, 177–188 (1988). https://doi.org/10.1007/BF02797134
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02797134