Testing of chelating agents and vitamins against lead toxicity using mammalian cell cultures†

(Note: The full text of this document is currently only available in the PDF Version )

Anna B. Fischer, Cristine Hess, Tilo Neubauer and Thomas Eikmann


Abstract

Mammalian cell cultures were used to determine the capacity of antidotes to modify (a) lead uptake, (b) lead toxicity and (c) lead release from cells. The following chelating agents were tested: Na, Ca-ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), nitriloacetic acid, ethylene glycol-bis(aminoethyl)tetraacetic acid (EGTA), D,L-mercaptosuccinic acid (MSA), meso-2,3-dimercaptopropanesuccinic acid (DMSA), D,L-2,3-dimercaptopropane-1-sulfonic acid (DMPS), penicillamine (PA), N-acetylpenicillamine (NAPA), and diethylcarbodithioate (DDTC). The following vitamins were tested: thiamine (B1), riboflavine (B2), pyridoxine (B6), cobalamin (B12) and ascorbic acid (C). Inhibition of lead uptake was produced by EDTA, EGTA, DMSA, DMPS, MSA, PA, NAPA and vitamins B1, B6 and C, vitamins B2 and B12 being ineffective. The same compounds reduced lead cytotoxicity. Interestingly DDTC and DTPA increased lead uptake, but did not exacerbate lead toxicity. Significant release of lead from preloaded cells was caused by DTPA, NAPA, DMPS and PA, while the other chelators were ineffective.


References

  1. J. Aaseth, J. Alexander and J. Deverill, Chem. Biol. Interact., 1981, 36, 287 CrossRef CAS.
  2. A. Bakka, J. Aaseth and H. E. Rugstad, Acta Pharmacol. Toxicol., 1981, 40, 432 Search PubMed.
  3. F. Borenfreund and J. A. Puerner, Toxicology, 1986, 39, 121 CrossRef.
  4. A. B. Fischer and G. Seibold, in International Conference on Heavy Metals in the Environment, ed. Lekkas, T. D., CEP Consultants, Edinburgh, 1985, vol. 2, pp. 110–112 Search PubMed.
  5. A. B. Fischer, Analyst, 1995, 120, 975 RSC.
  6. A. B. Fischer, A. Falk and G. Seibold, Plzen. Lek. Sb., Suppl., 1990, 62, 35 Search PubMed.
  7. S. J. Flora, S. Singh and S. K. Tandon, Z. Gesamte Hyg., 1984, 30, 409 Search PubMed.
  8. J. Prucha, Zbl. Bakt. Hyg., 1987, 185, 273 Search PubMed.
  9. A. B. Fischer, Xenobiotica, 1985, 15, 751 CAS.
  10. A. B. Fischer, Zelluläre Toxizität von Schwermetallen. Akute und chronische Wirkung auf Säugerzellkulturen, Wissenschaftlicher Fachverlag, Gieβen, Germany, 1995 Search PubMed.
  11. Deutsche Forschungsgemeinschaft Blei, in Analytische Methoden zur Prüfung gesundheitsschädlicher Arbeitsstoffe. Analysen im biologischen Material, ed. Greim, H., Verlag Chemie, Weinheim, 1980, vol. 2 Search PubMed.
  12. A. B. Fischer and A. Falk, in International Conference on Heavy Metals in the Environment, ed. Vernet, J. P., CEP Consultants, Edinburgh, 1989, vol. 1, pp. 410–413 Search PubMed.
  13. Z. F. Xu and M. M. Jones, Toxicology, 1988, 53, 277 CrossRef CAS.
  14. M. Dhawan, S. J. S. Flora, S. Singh and S. K. Tandon, Biochem. Int., 1989, 19, 1067 Search PubMed.
  15. K. Tsuchiya, in Handbook on the Toxicology of Metals, ed. Friberg, L., Nordberg, G. F., and Vouk, V. B., Elsevier, Amsterdam, 1986, vol. 2, 298–353 Search PubMed.
  16. P. Wiedemann, B. Fichtel and L. Szinicz, Biopharm. Drug Dispos., 1982, 3, 267 CAS.
  17. D. B. Wildenauer, H. Reuter and N. Wegner, Chem. Biol. Interact., 1982, 42, 165 CrossRef CAS.
  18. W. Zheng, R. M. Maiorino, K. Brendel and H. V. Aposhian, Fundam. Appl. Toxicol., 1990, 14, 598 CrossRef CAS.
  19. J. M. Lloblet, J. L. Domingo, J. L. Paternain and J. Corbella, Arch. Environ. Contamin. Toxicol., 1990, 19, 185.
  20. T. Twarog and G. Cherian, Toxicol. Appl. Pharmacol., 1984, 72, 550 CrossRef CAS.
  21. A. Catsch, Naturwissenschaften, 1968, 10, 473 CrossRef.
  22. J. J. Chisolm and D. J. Thomas, J. Pharmacol. Exp. Ther., 1985, 235, 665 Search PubMed.
  23. H. Foreman, C. C. Lusbaugh, M. Magee and G. Humanson, LAMS, 1960, 2445, 67 Search PubMed.
  24. P. B. Hammond, Toxicol. Appl. Pharmacol., 1971, 18, 296 CrossRef CAS.
  25. F. H. Kemper, F. W. Jekat, H. P. Bertram and R. Eckard, in Basic Science in Toxicology: Proceedings of the 5th International Congress of Toxicology, England 1989, London, 1990, p. 523 Search PubMed.
  26. J. H. Graziano, N. J. Lolacono and P. Meyer, J. Pediatr., 1988, 113, 751 CAS.
  27. H. L. Haust, M. Inwood, J. D. Spence, H. C. Poon and F. Peter, Clin. Biochem., 1989, 22, 189 CAS.
  28. J. G. Pounds, R. Wright and R. L. Kodell, Toxicol. Appl. Pharmacol., 1982, 66, 88 CrossRef CAS.
  29. J. F. Rosen, H. W. Kraner and K. W. Jones, Toxicol. Appl. Pharmacol., 1982, 64, 230 CrossRef CAS.
  30. J. J. Chisolm, Jr., Am. J. Dis. Child, 1987, 141, 1256 Search PubMed.
  31. S. K. Tandon, S. J. Flora and S. Singh, Ind. J. Med. Res., 1984, 80, 444 Search PubMed.
  32. S. K. Tandon, S. J. Flora and S. Singh, Pharmacol. Toxicol., 1987, 60, 62 Search PubMed.
  33. S. J. Flora and S. K. Tandon, Acta Pharmacol. Toxicol., 1986, 58, 274 Search PubMed.
Click here to see how this site uses Cookies. View our privacy policy here.