Biological Trace Element Research

, Volume 46, Issue 3, pp 247–259 | Cite as

Diethyl maleate, an in vivo chemical depletor of glutathione, affects the response of male and female rats to arsenic deprivation

  • Eric O. Uthus


An experiment was performed to determine the effect of diethyl maleate (DEM), and in vivo depletor of glutathione, on the response of male and female rats to arsenic deprivation. A 2×2×2 factorially arranged experiment used groups of six weanling Sprague-Dawley rats. Dietary variables were arsenic at 0 or 0.5 μg/g and DEM at 0 or 0.25%; the third variable was gender. Animals were fed for 10 wk a casein-ground corn based diet that contained amounts of calcium, phosphorus, and magnesium similar to the AIN-76 diet. DEM supplementation increased blood arsenic in both male and female rats; female rats had the greatest amount of arsenic in whole blood. Although female rats in general had a lower concentration of glutathione in liver, those fed no supplemental DEM, regardless of their arsenic status, had the lowest amounts. Compared to males, female rats had a lower activity of liver glutathione S-transferase (GST). Arsenic deprivation decreased, and DEM supplementation increased liver GST activity in both male and female rats. Lung GST activity was also increased by DEM supplementation in male, but not female, rats. The most striking finding of the study was that compared to males, females had extremely elevated kidney calcium concentrations, and that the elevation was exacerbated by arsenic deprivation. DEM supplementation also exacerbated the accumulation of calcium in the kidney of the female rats. The response of the rat to both DEM and arsenic was, for many variables, dependent on gender. This gender dependence may be explained by the differences in methionine metabolism between male and female rats. Thus, arsenic deprivation apparently can manifest itself differently depending on gender.

Index Entries

Arsenic deprivation arsenic essentiality gender diethyl maleate glutathione metabolism 


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  1. 1.
    E. Uthus and R. Poellot,Mag. Trace Elem. 10, 339–347 (1991-92).Google Scholar
  2. 2.
    E. Uthus and R. Poellot,J. Trace Elem. Exp. Med. 5, 153–164 (1992).Google Scholar
  3. 3.
    E. O. Uthus,Environ. Geochem. Health 14, 55–58 (1992).CrossRefGoogle Scholar
  4. 4.
    J. L. Plummer, B. R. Smith, H. Sies, and J. R. Bend,Methods in Enzymology, vol. 77, Jakoby, W. B., ed., Academic, New York, pp. 50–59 (1981).Google Scholar
  5. 5.
    E. Soon, N. Johnson, and B. C. F. Snider,J. Nutr. 114, 1853–1862 (1984).Google Scholar
  6. 6.
    J. De La Rosa and M. H. Stipanuk,Comp. Biochem. Physiol. B 81, 565–571 (1985).PubMedCrossRefGoogle Scholar
  7. 7.
    F. H. Nielsen and B. Bailey,Lab. Anim. Sci. 29, 502–506 (1979).PubMedGoogle Scholar
  8. 8.
    F. H. Nielsen, D. R. Myron, S. H. Givand, and D. A. Ollerich,J. Nutr. 105, 1607–1619 (1975).PubMedGoogle Scholar
  9. 9.
    O. W. Griffith,Methods of Enzymatic Analysis, vol. VIII, 3rd ed., Bergmeyer, H. U., ed., VCH, Deerfield Beach, FL, pp. 521–529 (1985).Google Scholar
  10. 10.
    W. H. Habig and W. B. Jakoby,Methods in Enzymology, vol. 77, Jakoby, W. B., ed., Academic, New York, pp. 218–231 (1981).Google Scholar
  11. 11.
    W. H. Habig and W. B. Jakoby,Methods in Enzymology, vol. 77, Jakoby, W. B., ed., Academic, New York, pp. 398–405 (1981).Google Scholar
  12. 12.
    F. H. Nielsen, T. J. Zimmerman, T. R. Shuler, B. Brossart, and E. O. Uthus,Trace Elem. Exp. Med. 2, 21–29 (1989).Google Scholar
  13. 13.
    SAS InstituteSAS User's Guide: Statistics, ed. 5, SAS Institute, Cary (1985).Google Scholar
  14. 14.
    J. L. Barnhart and J. Combes,J. Pharmacol. Exp. Ther. 206, 614 (1978).PubMedGoogle Scholar
  15. 15.
    R. F. Burk and M. A. Correia,Res. Comm. Chem. Pathol. Pharmacol. 24, 205 (1979).Google Scholar
  16. 16.
    J. Alexander and J. Aaseth,Nutr. Res. Suppl. 1, S-515–S-519 (1985).Google Scholar
  17. 17.
    I. Anundi, J. Högberg, and M. Vahter,FEBS Lett. 145, 285–288 (1982).PubMedCrossRefGoogle Scholar
  18. 18.
    S. Taketani, H. Kohno, T. Yoshinaga, and R. Tokunaga,Biochem. Int. 17, 665–672 (1988).PubMedGoogle Scholar
  19. 19.
    M. Hirose, M. Kagawa, K. Ogawa, A. Yamamoto, and N. Ito,Carcinogenesis 10, 2223–2226 (1989).PubMedCrossRefGoogle Scholar
  20. 20.
    W. H. Habig, M. J. Pabst, and W. B. Jakoby,J. Biol. Chem. 249, 7130–7139 (1974).PubMedGoogle Scholar
  21. 21.
    O. W. Griffith,Methods in Enzymology, vol. 77, Jakoby, W. B., ed., Academic, New York, pp. 59–63 (1981).Google Scholar
  22. 22.
    T. O. Eloranta, V. Martikainen, and T. K. Smith,Proc. Soc. Exp. Biol. Med. 194, 364–371 (1989).Google Scholar
  23. 23.
    G.-P. Xue and A. M. Snoswell,Comp. Biochem. Physiol. B 80, 489–494 (1985).PubMedCrossRefGoogle Scholar
  24. 24.
    A. J. Barak, H. C. Beckenhauer, and D. J. Tuma,Anal. Biochem. 127, 372–375 (1982).PubMedCrossRefGoogle Scholar
  25. 25.
    S. H. Mudd and J. R. Poole,Metabolism 24, 721–735 (1975).PubMedCrossRefGoogle Scholar
  26. 26.
    E. O. Uthus,Mag. Trace Elem. 9, 227–232 (1990).Google Scholar
  27. 27.
    E. O. Uthus,Proc. ND Acad. Sci. 47, 56 (1993).Google Scholar
  28. 28.
    H. Garcin, C. Suberville, and P. Higueret,Brit. J. Nutr. 61, 301–307 (1989).PubMedCrossRefGoogle Scholar
  29. 29.
    J. P. Buchet and R. Lauwerys,Arch. Toxicol. 57, 125–129 (1985).PubMedCrossRefGoogle Scholar
  30. 30.
    E. O. Uthus, R. Poellot, and F. H. Nielsen,6th International Trace Element Symposium 1989, M. Anke, W. Baumann, H. Bräunlich, Chr. Brückner, B. Groppel, and M. Grun, eds., Friedrich-Schiller-Universität, Jena, pp. 1013–1017 (1989).Google Scholar
  31. 31.
    W. E. Cornatzer, E. O. Uthus, J. A., Haning, and F. H. Nielsen,Nutr. Rep. Internat. 27, 821–829 (1983).Google Scholar
  32. 32.
    M. Vahter and E. Marafante,Spec. Publ.-R Soc. Chem. 66, 105–119 (1988).Google Scholar
  33. 33.
    C. Adams, J. Ritskes-Hoitinga, A. G. Lemmens, and A. C. Beynen,Nutr. Rep. Internat. 40, 923–929 (1989).Google Scholar
  34. 34.
    B. G. Shah, K. D. Trick, and B. Belonje,Nutr. Res. 6, 559–570 (1986).CrossRefGoogle Scholar
  35. 35.
    B. G. Shah, and B. Belonje,Nutr. Res. 11, 385–390 (1991).CrossRefGoogle Scholar
  36. 36.
    P. G. Reeves, K. L. Rossow, and J. Lindlauf,J. Nutr.,123, 1923–1931 (1993).PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 1994

Authors and Affiliations

  • Eric O. Uthus
    • 1
  1. 1.Agricultural Research Service, Grand Forks Human Nutrition Research CenterUnited States Department of AgricultureGrand Forks

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