On the Role of Metallothionein in Cadmium Induced Renal Toxicity

  • Monica Nordberg
  • G. F. Nordberg
Part of the Experientia Supplementum book series (EXS, volume 52)


Metallothionein plays an important role in the metabolism and toxicity of cadmium. Human beings are exposed to increasing amounts of cadmium. The critical organ in long term cadmium exposure is the kidney. Some groups in the population fall within the risk zone for developing renal tubular dysfunction from cadmium exposure. After absorption, cadmium is to a large extent distributed to the liver where it is bound to and induces the synthesis of metallothionein. Subsequently metallothionein-bound cadmium is slowly released into blood and efficiently taken up by renal tubular cells after glomerular filtration. The biological half-time of cadmium in the human kidney is considered to be very long: 10–15 years and this explains the life-long accumulation of cadmium, reaching a toxic concentration of approximately 200 ug/g in excessively exposed individuals. Human adult renal metallothionein has a natural content of cadmium which also induces the resynthesis of this protein upon its catabolism. This could be one explanation of the long biological half-time which has been reported for cadmium. Injection of metallothionein-bound cadmium can induce renal tubular kidney dysfunction at lower renal cadmium concentrations (10–20 ug/g), probably because of the fast catabolism and relatively slow synthesis of metallothionein in renal cells. A model of these and other mechanisms causing tubular kidney damage in cadmium exposure is presented.


Renal Tubular Cell Cadmium Exposure Risk Zone Term Exposure Karolinska Institute 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Task Group on Metal Toxicity in Effects and Dose-Response Relationships of Toxic Metals. G.F. Nordberg ed., Elsevier Amsterdam, 1976.Google Scholar
  2. 2.
    Nordberg, G.F. (1972) Env. Physiol. Biochem. 2, 7–36.Google Scholar
  3. 3.
    Nordberg, M. (1978) Env. Res. 15, 381–404.CrossRefGoogle Scholar
  4. 4.
    Nordberg, G.F., Piscator, M. and Nordberg, M. (1971) Acta Pharmacol. Toxicol. 30, 289–295.CrossRefGoogle Scholar
  5. 5.
    Garty, M., Wong, K.-L. and Klaassen, C.O. (1981) Toxicol. Appl. Pharmacol. 59, 548–554.CrossRefGoogle Scholar
  6. 6.
    Cherian, M.G., Goyer, R.A. and Delaquerriere-Richardson, L. (1976) Toxicol. Appl. Pharmacol. 38, 399–408.CrossRefGoogle Scholar
  7. 7.
    Nordberg, G.F. (1982) In “Nephrotoxic Mechanisms of Drugs and Environmental Toxins”, G. Porter ed., Plenum Press, New York, pp. 285–303.CrossRefGoogle Scholar
  8. 8.
    Fowler, B.A. and Nordberg, G.F. (1975) Int. Conf. on Heavy Metals in the Environment, Toronto, Canada, B52–53.Google Scholar
  9. 9.
    Fowler, B.A. and Nordberg, G.F. (1978) Toxicol. Appl. Pharmacol. 46, 609–623.CrossRefGoogle Scholar
  10. 10.
    Squibb, K.S. and Fowler, B.A. (1984) Env. Health Persp. 54, 31–35.CrossRefGoogle Scholar
  11. 11.
    Nordberg, M. and Nordberg, G.F. (1975) Env. Health Persp. 12, 103–108.CrossRefGoogle Scholar
  12. 12.
    Nordberg, G.F., Goyer, R.A. and Nordberg, M. (1975) Arch. Pathol. 99, 192–197.Google Scholar
  13. 13.
    Nordberg, M. (1984) Env. Health. Persp. 54, 13–20.CrossRefGoogle Scholar
  14. 14.
    Piscator, M (1964) Nord. Hyg. Tidskr. 45, 76–82.Google Scholar
  15. 15.
    Nordberg, G.F., Piscator, M. and Lind, B. (1971) Acta Pharmacol. Toxicol. 29, 456–470.CrossRefGoogle Scholar
  16. 16.
    Nordberg, M., Elinder, C.G. and Rahnster, B. (1979) Env. Res. 20, 341–350.CrossRefGoogle Scholar
  17. 17.
    Elinder, C.G., Nordberg, M., Palm, B. and Piscator, M. (1981) Env. Res. 26, 22–32.CrossRefGoogle Scholar
  18. 18.
    Elinder, C.G., Lundgren, G., Nordberg, M., Palm, B. and Piscator, M. (1984) Env. Health Perspect. 54, 275–280.CrossRefGoogle Scholar
  19. 19.
    Nordberg, G.F. (1971) Environ. Physiol. Biochem. 1, 171–187.Google Scholar
  20. 20.
    Kägi, J.H.R. and Nordberg, M. (1979) eds. Metallothionein, Birkhäuser Verlag, Basel, pp. 71–76.CrossRefGoogle Scholar
  21. 21.
    Cherian, M.G. and Nordberg, M. (1983) Toxicology 28, 1–15.CrossRefGoogle Scholar
  22. 22.
    Petering, D.H., Loftsgaarden, J., Schneider, J. and Fowler, B. (1984) Env. Health Perspect. 54, 73–81.CrossRefGoogle Scholar
  23. 23.
    Piscator, M. (1966) Doctoral Thesis, Karolinska Institute, Stockholm, Sweden.Google Scholar
  24. 24.
    Nordberg, G.F. and Piscator, M. (1972) Env. Physiol. Biochem. 2, 37–49.Google Scholar
  25. 25.
    Waku, K. (1984) Env. Health Perspect. 54, 37–44.CrossRefGoogle Scholar
  26. 26.
    Nordberg, G.F., Kjellström, T. and Nordberg, M. (1985) In: “Cadmium and Health”, L. Friberg, C.G. Elinder, T. Kjellström and G.F. Nordberg, eds., CRC-Press, Florida.Google Scholar
  27. 27.
    Rugstad, H.E. and Norseth, T. (1975) Nature 136–137.Google Scholar
  28. 28.
    Bakka, A. (1983) Doctoral Thesis, University of Oslo, Oslo, Norway.Google Scholar

Copyright information

© Springer Basel AG 1987

Authors and Affiliations

  • Monica Nordberg
    • 1
  • G. F. Nordberg
    • 2
  1. 1.Department of Environmental HygieneKarolinska InstituteStockholmSweden
  2. 2.Department of Environmental MedicineUmeå UniversityUmeåSweden

Personalised recommendations