Evaluating the role of zinc in the occurrence of fibrosis of the skin: a preclinical study

J Magn Reson Imaging. 2009 Aug;30(2):374-83. doi: 10.1002/jmri.21845.


Purpose: To investigate the possible role of Zn as a trigger for NSF we were using a previously established preclinical model. The depletion of endogenous Zinc ions (Zn) caused by the administration of gadolinium-based contrast agents (GBCAs) has been suggested as a possible pathomechanism for nephrogenic systemic fibrosis (NSF).

Materials and methods: In the Zn supplementation study, rats were injected with Gadodiamide, Omniscan, and Magnevist with or without Zn supplementation. In the Zn depletion study, animals were kept on a Zn-deficient diet or a special control diet and received injections of Omniscan, OptiMARK, Magnevist, Gadovist, and Gd-EDTA. Gd, Zn, and Cu concentrations in tissue were measured and histology of the skin was performed.

Results: As seen in earlier studies, a difference in Gd concentration in the skin was observed following treatment with the different GBCAs. High Gd concentration in the skin correlated with the occurrence of NSF-like skin lesions. We observed no differences in the occurrence of skin lesions between the Zn supplementation and the Zn-deficient groups compared to their respective control groups.

Conclusion: We found no significant effect of Zn on the initiation of NSF-like skin lesions. The results further support data from previous studies highlighting the importance of complex stability of the investigated GBCAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contrast Media / pharmacokinetics*
  • Contrast Media / toxicity*
  • Copper / metabolism
  • Edetic Acid / pharmacokinetics
  • Edetic Acid / toxicity
  • Gadolinium DTPA / pharmacokinetics
  • Gadolinium DTPA / toxicity
  • Nephrogenic Fibrosing Dermopathy / chemically induced*
  • Organometallic Compounds / pharmacokinetics
  • Organometallic Compounds / toxicity
  • Rats
  • Rats, Wistar
  • Skin / metabolism
  • Zinc / metabolism*
  • Zinc / pharmacology*


  • Contrast Media
  • Organometallic Compounds
  • gadolinium EDTA
  • gadobutrol
  • Copper
  • gadodiamide
  • Edetic Acid
  • Zinc
  • Gadolinium DTPA
  • gadoversetamide