Skip to main content
NCBI home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1984 Mar;54:243–248. doi: 10.1289/ehp.8454243

Chelation of cadmium without increased renal cadmium deposition.

M G Cherian
PMCID: PMC1568164  PMID: 6734559

Abstract

Cadmium (Cd) is mainly accumulated in liver and kidney bound to metallothionein (MT) and excreted very slowly from the body. In chronic exposure, Cd is gradually transported from liver to kidney; the renal toxic effects appear when renal Cd concentration exceeds the critical concentration. In order to prevent the Cd-induced renal disease, it is important to control the movement of Cd to the kidney and its renal deposition. However, the chelation of Cd from liver is difficult because of the high affinity of intracellular MT for Cd. A number of chelating agents containing both carboxyl and thiol groups were able to mobilize and excrete Cd more easily in a short time (1/2 hr) after Cd exposure than longer times (24 hr), after MT synthesis. The renal deposition of Cd increased on BAL (2,3-dimercaptopropanol) treatment a short time (1/2 hr) after Cd exposure. However, it was observed that if BAL was administered 24 hr after Cd exposure, it could mobilize Cd from hepatic MT and increase the biliary excretion of Cd without any increase in renal Cd concentration. Studies using a number of structurally related thiols (mono-, di- and trithiols) showed that the major structural requirement for in vivo chelation of Cd from intracellular MT were the vicinal thiol groups on an aliphatic chain, and lipophilicity. BAL was the most effective of all the compounds studied and it did not mobilize Cd to the kidney, when most of the intracellular Cd was bound to MT. Furthermore, a delayed treatment with BAL or DTPA (diethylenetriamine pentaacetic acid) after synthesis of MT resulted in an increase in fecal or urinary excretion of Cd in rat model experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
243

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersen O., Hägerstrand I., Nordberg G. F. Effect of the chelating agent sodium tripolyphosphate on cadmium toxicity in mice. Environ Res. 1982 Oct;29(1):54–61. doi: 10.1016/0013-9351(82)90006-8. [DOI] [PubMed] [Google Scholar]
  2. Aposhian H. V. DMSA and DMPS--water soluble antidotes for heavy metal poisoning. Annu Rev Pharmacol Toxicol. 1983;23:193–215. doi: 10.1146/annurev.pa.23.040183.001205. [DOI] [PubMed] [Google Scholar]
  3. BONNELL J. A., ROSS J. H., KING E. Renal lesions in experimental cadmium poisoning. Br J Ind Med. 1960 Jan;17:69–80. doi: 10.1136/oem.17.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bernard A., Roels H., Hubermont G., Buchet J. P., Masson P. L., Lauwerys R. R. Characterization of the proteinuria in cadmium-exposed workers. Int Arch Occup Environ Health. 1976 Oct 21;38(1):19–30. doi: 10.1007/BF00378317. [DOI] [PubMed] [Google Scholar]
  5. Cantilena L. R., Jr, Klaassen C. D. Comparison of the effectiveness of several chelators after single administration on the toxicity, excretion, and distribution of cadmium. Toxicol Appl Pharmacol. 1981 May;58(3):452–460. doi: 10.1016/0041-008x(81)90098-3. [DOI] [PubMed] [Google Scholar]
  6. Cherian M. G. Biliary excretion of cadmium in rat. II. The role of metallothionein in the hepatobiliary transport of cadmium. J Toxicol Environ Health. 1977 Mar;2(4):955–961. doi: 10.1080/15287397709529494. [DOI] [PubMed] [Google Scholar]
  7. Cherian M. G. Biliary excretion of cadmium in rat. III. Effects of chelating agents and change in intracellular thiol content on biliary transport and tissue distribution of cadmium. J Toxicol Environ Health. 1980 Mar;6(2):379–391. doi: 10.1080/15287398009529858. [DOI] [PubMed] [Google Scholar]
  8. Cherian M. G. Chelation of cadmium with BAL and DTPA in rats. Nature. 1980 Oct 30;287(5785):871–872. doi: 10.1038/287871a0. [DOI] [PubMed] [Google Scholar]
  9. Cherian M. G., Goyer R. A. Methallothioneins and their role in the metabolism and toxicity of metals. Life Sci. 1978 Jul 3;23(1):1–9. doi: 10.1016/0024-3205(78)90317-x. [DOI] [PubMed] [Google Scholar]
  10. Cherian M. G., Onosaka S., Carson G. K., Dean P. A. Biliary excretion of cadmium in rat. V. Effects of structurally related mercaptans on chelation of cadmium from metallothionein. J Toxicol Environ Health. 1982 Mar;9(3):389–399. doi: 10.1080/15287398209530172. [DOI] [PubMed] [Google Scholar]
  11. Cherian M. G., Rodgers K. Chelation of cadmium from metallothionein in vivo and its excretion in rats repeatedly injected with cadmium chloride. J Pharmacol Exp Ther. 1982 Sep;222(3):699–704. [PubMed] [Google Scholar]
  12. Cherian M. G., Vostal J. J. Biliary excretion of cadmium in rat. I. Dose-dependent biliary excretion and the form of cadmium in the bile. J Toxicol Environ Health. 1977 Mar;2(4):945–954. doi: 10.1080/15287397709529493. [DOI] [PubMed] [Google Scholar]
  13. DALHAMN T., FRIBERG L. Dimercaprol (2, 3-dimercaptopropanol) in chronic cadmium poisoning. Acta Pharmacol Toxicol (Copenh) 1955;11(1):68–71. doi: 10.1111/j.1600-0773.1955.tb00203.x. [DOI] [PubMed] [Google Scholar]
  14. Engström B., Nordberg G. F. Effects of detergent formula chelating agents on the metabolism and toxicity of cadmium in mice. Acta Pharmacol Toxicol (Copenh) 1978 Nov;43(5):387–397. doi: 10.1111/j.1600-0773.1978.tb02283.x. [DOI] [PubMed] [Google Scholar]
  15. Engström B., Norin H., Jawaid M., Ingman F. Influence of different Cd-EDTA complexes on distribution and toxicity of cadmium in mice after oral or parenteral administration. Acta Pharmacol Toxicol (Copenh) 1980 Mar;46(3):219–234. doi: 10.1111/j.1600-0773.1980.tb02446.x. [DOI] [PubMed] [Google Scholar]
  16. Eybl V., Sýkora J., Mertl F. Wirkung von CaADTA und CaDTPA bei der Kadmiumvergiftung. Acta Biol Med Ger. 1966;17(2):178–185. [PubMed] [Google Scholar]
  17. FRIBERG L. Edathamil calcium-disodium in cadmium poisoning; a study of the excretion, distribution, and toxicity of cadmium in animals. AMA Arch Ind Health. 1956 Jan;13(1):18–23. [PubMed] [Google Scholar]
  18. Jones M. M., Weaver A. D., Weller W. L. The relative effectiveness of some chelating agents as antidotes in acute cadmium poisoning. Res Commun Chem Pathol Pharmacol. 1978 Dec;22(3):581–588. [PubMed] [Google Scholar]
  19. KAGI J. H., VALLEE B. L. Metallothionein: a cadmium and zinc-containign protein from equine renal cortex. II. Physico-chemical properties. J Biol Chem. 1961 Sep;236:2435–2442. [PubMed] [Google Scholar]
  20. Kazantzis G. Renal tubular dysfunction and abnormalities of calcium metabolism in cadmium workers. Environ Health Perspect. 1979 Feb;28:155–159. doi: 10.1289/ehp.7928155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kjellström T., Shiroishi K., Evrin P. E. Urinary beta2-microglobulin excretion among people exposed to cadmium in the general environment: an epidemiological study in cooperation between Japan and Sweden. Environ Res. 1977 Apr;13(2):318–344. doi: 10.1016/0013-9351(77)90107-4. [DOI] [PubMed] [Google Scholar]
  22. Klaassen C. D. Effect of metallothionein on hepatic disposition of metals. Am J Physiol. 1978 Jan;234(1):E47–E53. doi: 10.1152/ajpendo.1978.234.1.E47. [DOI] [PubMed] [Google Scholar]
  23. Kojima S., Kiyozumi M., Saito K. Studies on poisonous metals. II. Effect of chelating agents on excretion of cadmium through bile and gastrointestinal mucosa in rats. Chem Pharm Bull (Tokyo) 1976 Jan;24(1):16–21. doi: 10.1248/cpb.24.16. [DOI] [PubMed] [Google Scholar]
  24. Murakami M., Webb M. A morphological and biochemical study of the effects of L-cysteine on the renal uptake and nephrotoxicity of cadmium. Br J Exp Pathol. 1981 Apr;62(2):115–130. [PMC free article] [PubMed] [Google Scholar]
  25. PISCATOR M. OM KADMIUM I NORMALA MAENNISKONJURAR SAMT REDOGOERELSE FOER ISOLERING AV METALLOTHIONEIN UR LEVER FRAN KADMIUMEXPONERADE KANINER. Nord Hyg Tidskr. 1964;45:76–82. [PubMed] [Google Scholar]
  26. PISCATOR M. Proteinuria in chronic cadmium poisoning. 1. An electrophoretic and chemical study of urinary and serum proteins from workers with chronic cadmium poisoning. Arch Environ Health. 1962 Jun;4:607–621. doi: 10.1080/00039896.1962.10663220. [DOI] [PubMed] [Google Scholar]
  27. Planas-Bohne F., Lehmann M. Influence of chelating agents on the distribution and excretion of cadmium in rats. Toxicol Appl Pharmacol. 1983 Mar 15;67(3):408–416. doi: 10.1016/0041-008x(83)90325-3. [DOI] [PubMed] [Google Scholar]
  28. Scheuhammer A. M., Cherian M. G. The distribution and excretion of manganese: the effects of manganese dose, L-dopa, and pretreatment with zinc. Toxicol Appl Pharmacol. 1982 Sep 15;65(2):203–213. doi: 10.1016/0041-008x(82)90002-3. [DOI] [PubMed] [Google Scholar]
  29. Schubert J., Derr S. K. Mixed ligand chelate therapy for plutonium and cadmium poisoning. Nature. 1978 Sep 28;275(5678):311–313. doi: 10.1038/275311a0. [DOI] [PubMed] [Google Scholar]
  30. Stowe H. D. Biliary excretion of cadmium by rats: effects of zinc, cadmium, and selenium pretreatments. J Toxicol Environ Health. 1976 Sep;2(1):45–53. doi: 10.1080/15287397609529416. [DOI] [PubMed] [Google Scholar]
  31. Von Burg R., Smith J. C. Biliary mobilization of cadmium by 2,3-dimercaptopropanol and some related compounds. J Toxicol Environ Health. 1980 Jan;6(1):75–85. doi: 10.1080/15287398009529832. [DOI] [PubMed] [Google Scholar]
  32. Waalkes M. P., Watkins J. B., Klaassen C. D. Minimal role of metallothionein in decreased chelator efficacy for cadmium. Toxicol Appl Pharmacol. 1983 May;68(3):392–398. doi: 10.1016/0041-008x(83)90283-1. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES