NDLI: The gadolinium-based contrast agent Omniscan® promotes in vitro fibroblast survival through in situ precipitation

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The gadolinium-based contrast agent Omniscan® promotes in vitro fibroblast survival through in situ precipitation

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Metallomics Vol - 7 Issue - 6

Metallomics Vol - 7 Issue - 5

Metallomics Vol - 7 Issue - 4

Metallomics Vol - 7 Issue - 3

Metallomics Vol - 7 Issue - 2

The gadolinium-based contrast agent Omniscan® promotes in vitro fibroblast survival through in situ precipitation

Content Provider	Royal Society of Chemistry (RSC)
Author	Ma, Xiao-Jie Yang, Xiao-Gai Fan, Yun-Zhou Li, Jin-Xia Feng, Min
Copyright Year	2015
Abstract	The current study aims to explore how the gadolinium (Gd)-based contrast agent (GBCA) Omniscan® enhanced cell viability of murine fibroblasts. The results of scanning electron microscopy showed that Omniscan® can precipitate in cell culture media and deposit on cell membranes. Energy-dispersive X-ray analysis and Fourier-transform infrared spectroscopy demonstrated the presence of Gd and phosphates in the agglomerated particles. By filtering the Omniscan®-containing medium through a 220 nm filter, it can be clearly found that the increased cell viability should be mainly attributed to the insoluble species of gadolinium rather than to chelated gadolinium. Moreover, the effects of other gadolinium-based contrast agents, Magnevist® and Dotarem®, were compared with that of Omniscan®. It is noted that the three contrast agents differed in their ability to induce cell viability, which is possibly ascribed to the different chemical stabilities of gadolinium chelates as demonstrated by the attenuation in cell growth upon the addition of excess ligands to the compounds. The results of flow cytometry analysis also showed that Omniscan® can promote cell growth via an increase in the S-phase cell population as evidenced by the elevated levels of cell cycle associated proteins cyclin D, cyclin A and the phosphorylated Rb protein. Furthermore, our results revealed that integrin-mediated signaling may play an important role in both Omniscan® and Magnevist®-enhanced focal adhesion formation since the blockade of integrins decreased the level of ERK phosphorylation induced by the two GBCAs. Taken together, these data suggested that in situ gadolinium phosphate precipitation formation mediated Omniscan®-promoted fibroblast survival, which is similar to that of gadolinium chloride. It was demonstrated that the application of GBCAs with more stable thermodynamic stability may cause less dissociation of the gadolinium ion and thus resulted in less precipitation, finally leading to lower occurrence of nephrogenic systemic fibrosis. The obtained results would also be helpful for the development of safe gadolinium-based contrast agents.
Starting Page	1103
Ending Page	1110
Page Count	8
File Format	HTM / HTML PDF
ISSN	17565901
Volume Number	7
Issue Number	7
Journal	Metallomics
DOI	10.1039/c5mt00055f
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Cell culture Flow cytometry Phosphorylation Focal adhesion Cyclin Mitogen-activated protein kinase Gadolinium Contrast medium Ion Fourier-transform infrared spectroscopy Dissociative Scanning electron microscope Protein X-ray crystallography Gadodiamide Chloride Cell cycle Fibrosis Gadopentetic acid Fibroblast
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

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The gadolinium-based contrast agent Omniscan® promotes in vitro fibroblast survival through in situ precipitation