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


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.


CONCLUSIONS
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.
Pietsch
Hubertus
H
Contrast Media Research, Bayer Schering Pharma AG, Berlin, Germany.
Pering
Christiane
C
Lengsfeld
Philipp
P
Walter
Jakob
J
Steger-Hartmann
Thomas
T
Golfier
Sven
S
Frenzel
Thomas
T
Hütter
Joachim
J
Weinmann
Hans-Joachim
HJ
Sieber
Martin A
MA
D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics* / Q000633:toxicity*; D003300:Copper / Q000378:metabolism; D004492:Edetic Acid / Q000493:pharmacokinetics / Q000633:toxicity; D019786:Gadolinium DTPA / Q000493:pharmacokinetics / Q000633:toxicity; D054989:Nephrogenic Fibrosing Dermopathy / Q000139:chemically induced*; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology*
D003287:Contrast Media; D009942:Organometallic Compounds; C041365:gadolinium EDTA; C090600:gadobutrol; D003300:Copper; C064925:gadodiamide; D004492:Edetic Acid; D015032:Zinc; D019786:Gadolinium DTPA; C112666:gadoversetamide