2020 Fiscal Year Annual Research Report
Potential mechanism of Gadolinium penetration via intact blood-brain barriers and the effect of Gd retention to brain cancer proliferation
| Project/Area Number |
19K17224
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| Research Institution | Gunma University |
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Principal Investigator |
K AchmadA.P. 群馬大学, 大学院医学系研究科, 助教 (70806439)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | contrast agents / Gadolinium / Transmetallation / Gadolinium deposition / NSF / neutrophil elastase / astroglioma / meduloblastoma |
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| Outline of Annual Research Achievements |
The Gd retention phenomenon has now proposed worldwide as Gadolinium Deposition Disease (GDD), and amongst the target organs are brain and skin. Previously we observed the possibility of transferrin as a transporter of Gd into the brain and the effect of GBCAs on the Purkinje cells when incubated with Fe2+. We found no significant differences in Gd concentration when Gadolinium-based contrast agents (GBCA) were incubated with transferrin. We also observed that although Fe2+ increased the effect of gadopentetate to the dendrite arborization, it did not increase the effect of gadobutrol, suggesting that the difference in chelate structures may be important for the toxicity effect of Gd.
We investigated the involvement of neutrophil elastase (NE) in the development of NSF-like skin lesions post-injections of linear GBCAs in renal failure mouse models. Fibrotic markers were increased in the skin on mice injected with gadodiamide, while only Collagen 1α and TGF-β mRNA expression were higher in the gadopentetate group. Gd concentration in the skin of the gadodiamide group was significantly higher than in the gadopentetate group. NE activity in the blood serum and the expression of skin NE was significantly higher in the GBCA-treated mice compared to the control. NE may be involved in the development of fibrosis linked to the GBCAs injections in renal failure mouse models.
We also investigated the GBCA effect on the C6-astroglioma and TE761-medulloblastoma in-vitro. GBCAs significantly increase the C6 proliferation, but the effect was less significant in TE761 cells.
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