AGE

, Volume 3, Issue 2, pp 33–37 | Cite as

Phenytoin-induced serum copper and ceruloplasmin in C57BL/6J mice of different ages

  • Harold R. Massie
  • James R. Colacicco
  • Valerie R. Aiello
Article

Abstract

Phenytoin (diphenyihydantoln) given orally to male C57BL/6J mice increased the serum copper and ceruloplasmin concentrations. Young adult mice showed a maximum increase of 107% in ceruloplasmin accompanied by a 102% increase in copper. The ceruloplasmin of middle-aged mice increased 53% and the copper 64%. For old mice the corresponding increases were 20 and 21%. Phenytoin was toxic to old mice, and middle-aged mice experienced a higher rate of death when given phenytoin for 167 days.

After 14 days, phenytoin decreased liver copper by 18% without significantly changing copper levels in kidney, brain or heart. Feeding phenytoin for 167 days lowered liver copper by 14%, increased kidney by 9% and brain by 25%. Copper in the heart remained unchanged.

We proposed that the status of copper in the brain may be important in epilepsy.

Keywords

Copper Adult Mouse Maximum Increase Copper Level Serum Copper 

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References

  1. 1.
    Woodbury, D.M., and Fingl, E.: Drugs effective in the therapy of the epilepsies, in the Pharmacological Basis of Therapeutics, edited by Goodman, L.S., and Gilman, A., 5th edition, MacMillan Pub. Co., New York, 1975, pp. 201–226.Google Scholar
  2. 2.
    Peter, T., Ross, D., Duffield, A., Luxton, M., Harper, R., Hunt, D., and Sloman, G.: Effect on survival after myocardial infarction of long-term treatment with phenytoin. British Heart J., 40:1356–1360, 1978.Google Scholar
  3. 3.
    Cantu, R.C., and Schwab, R.S.: Ceruloplasmin rise and PBI fall in serum due to diphenylhydantoin. Arch. Neurol., 15:393–396, 1966.PubMedGoogle Scholar
  4. 4.
    Taylor, J.D., Krahn, P.M., and Higgins, T.N.: Serum copper levels and diphenylhydantoin. Am. J. Clin. Path., 61:577–578, 1974.PubMedGoogle Scholar
  5. 5.
    Cox, D.W.: Factors influencing serum ceruloplasmin in normal individuals. J. Lab. Clin. Med., 68: 893–904, 1966.PubMedGoogle Scholar
  6. 6.
    Markowitz, H., Gubler, C.J., Mahoney, J.P., Cartwright, G.E. and Wintrobe, M.: Studies on copper metabolism. J. Clin. Invest., 34:1498–1508, 1955.PubMedCrossRefGoogle Scholar
  7. 7.
    Lifschitz, M.D., and Henkin, R.I.: Circadian variation in copper and zinc in man. J. Applied Physiol., 31:88–92, 1971.Google Scholar
  8. 8.
    Dowdy, R.P., and Dohm, G.L.: Effect of training and exercise in serum ceruloplasmin in rats. Proc. Soc. Exp. Biol. and Med., 139:489-491, 1972.Google Scholar
  9. 9.
    Davidoff, G.N., Votaw, M.L., Coon, W.W., Hultquist, D.E., Filter, B.J., and Wexler, S.A.: Elevations in serum copper, erythrocyte copper, and ceruloplasmin concentrations in smokers. Am. J. Clin. Pathol., 70:790–792, 1976.Google Scholar
  10. 10.
    Shields, G.S., Markowitz, H., Cartwright, G.E., and Wintrobe, M.M.: Blood copper proteins in human Subjects, in Metal Binding in Medicine, edited by Seven, M.J. and Johnson, L.A., Lippincott Co., Philadelphia, 1960, pp. 259–264.Google Scholar
  11. 11.
    Alginger, P., Kolarz, G., and Willvonseder, R.: Copper in ankylosing spondylitis and rheumatoid arthritis. Scand. J. Rheumantology., 7:75–78, 1978.Google Scholar
  12. 12.
    Viersieck, J., Barbier, F., Speecke, A., and Hoste, J.: Influence of myocardial infarction on serum manganese, copper, and zinc concentrations. Clin. Chem., 21:578–581, 1975.Google Scholar
  13. 13.
    Harman, D.: Role of serum copper in coronary atherosclerosis. Circulation, 28:658, 1963.Google Scholar
  14. 14.
    Bustamento, J., Martin, M.C., Fernandez, J., and Ortiz, O.: Zinc, copper and ceruloplasmin in arteriosclerosis. Biomedicine, 25:244–245, 1976.Google Scholar
  15. 15.
    Krishnamachari, K.A.V.R.: Some aspects of copper metabolism in pellagra. Amer. J. Clin. Nutr., 27: 108–111, 1974.PubMedGoogle Scholar
  16. 16.
    Zackheim, H.S., and Wolf, P.: Serum copper in psoriasis and other dermatoses. J. Invest. Derm., 58: 28–32, 1972.PubMedCrossRefGoogle Scholar
  17. 17.
    Herring, W.B., Leavell, B.S., Paixao, L.M., and Yoe, J.H.: Trace metals in human plasma and red blood cells. Amer. J. Clin. Nutr., 8:846–854, 1960.PubMedGoogle Scholar
  18. 18.
    Harman, D.: The free radical theory of aging: effect of age on serum copper levels. J. Gerontol., 20: 151–153, 1965.PubMedGoogle Scholar
  19. 19.
    Yunice, A.A., Lindeman, R.D., Czerwinski, A.W., and Clark, M.: Influence of age and sex on serum copper and ceruloplasmin levels. J. Gerontol., 29:277–281, 1974.PubMedGoogle Scholar
  20. 20.
    Massie, H.R., Colacicco, J.R., and Aiello, V.R.: Changes with age in copper and ceruloplasmin in serum from humans and C57BL/6J mice. Age, 2:97–101, 1979.Google Scholar
  21. 21.
    Ravin, H.A.: An improved colorimetric enzymatic assay of ceruloplasmin. J. Lab. Clin. Med., 58: 161–168, 1961.PubMedGoogle Scholar
  22. 22.
    Massie, H.R., and Aiello, V.R.: Changes with age in cadmium and copper levels in C57BL/6J mice. Mech. Age. Devel., 11:219–225, 1979.CrossRefGoogle Scholar
  23. 23.
    Massie, H.R., Aiello, V.R., and Iodice, A.A.: Changes with age in copper and superoxide dismutase levels in brains of C57BL/6J mice. Mech. Age. Devel., 10:93–99, 1979.CrossRefGoogle Scholar
  24. 24.
    Schroeder, H.A., Nason, A.P., Tipton, I.H., and Basassa, J.J.: Essential trace metals in man: Copper. J. Chron. Dis., 19:1007–1034, 1966.PubMedCrossRefGoogle Scholar
  25. 25.
    Keen, C.L., and Hurley, L.S.: Superoxide dismutase activity in the crinkled mutant mouse: ameliorative effects of dietary copper supplementation. Proc. Soc. Exp. Biol. and Med., 162: 152–156, 1979.Google Scholar

Copyright information

© American Aging Association, Inc. 1980

Authors and Affiliations

  • Harold R. Massie
    • 1
  • James R. Colacicco
    • 1
  • Valerie R. Aiello
    • 1
  1. 1.Masonic Medical Research LaboratoryUtica

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