Gadolinium tissue deposition in the periodontal ligament of mice with reduced renal function exposed to Gd-based contrast agents

Riccarda Delfino, Matteo Biasotto, Riccardo Candido, Matteo Altissimo, Marco Stebel, Murielle Salomè, Johannes T. van Elteren, Katarina Vogel Mikuš, Cristina Zennaro, Martin Šala, Riccardo Addobbati, Giuliana Tromba, Lorella Pascolo

Research output: Contribution to journalArticle

Abstract

Gadolinium deposition in tissue is linked to nephrogenic systemic fibrosis (NSF): a rare disorder occurring in patients with severe chronic kidney disease and associated with administration of Gd-based contrast agents (GBCAs) for Magnetic Resonance Imaging (MRI). It is suggested that the GBCAs prolonged permanence in blood in these patients may result in a Gd precipitation in peripheral or central organs, where it initiates a fibrotic process. In this study we investigated new sites of retention/precipitation of Gd in a mouse model of renal disease (5/6 nephrectomy) receiving two doses (closely after each other) of a linear GBCA. Two commercial GBCAs (Omniscan® and Magnevist®) were administered at doses slightly higher than those used in clinical practice (0.7 mmol/kg body weight, each). The animals were sacrificed one month after the last administration and the explanted organs (kidney, liver, femur, dorsal skin, teeth) were analysed by X-ray fluorescence (XRF) at two synchrotron facilities. The XRF analysis with a millimetre-sized beam at the SYRMEP beamline (Elettra, Italy) produced no detectable levels of Gd in the examined tissues, with the notable exception of the incisors of the nephrectomised mice. The XRF analyses at sub-micron resolution performed at ID21 (ESRF, France) allowed to clearly localize Gd in the periodontal ligaments of teeth both from Omniscan® and Magnevist® treated nephrectomised mice. The latter results were further confirmed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The study prompts that prolonged permanence of GBCAs in blood may result in Gd retention in this particular muscular tissue, opening possibilities for diagnostic applications at this level when investigating Gd-related toxicities.

Original languageEnglish
Pages (from-to)157-167
Number of pages11
JournalToxicology Letters
Volume301
DOIs
Publication statusPublished - Feb 1 2019

Fingerprint

Periodontal Ligament
Ligaments
Gadolinium
gadodiamide
Contrast Media
Tissue
Kidney
Gadolinium DTPA
Fluorescence
X-Rays
X rays
Tooth
Blood
Nephrogenic Fibrosing Dermopathy
Inductively coupled plasma mass spectrometry
Synchrotrons
Laser Therapy
Laser ablation
Incisor
Nephrectomy

Keywords

  • 5/6 nephrectomy
  • Gadolinium
  • GBCAs
  • MRI contrast agent
  • Periodontal ligament
  • XRF

ASJC Scopus subject areas

  • Toxicology

Cite this

Gadolinium tissue deposition in the periodontal ligament of mice with reduced renal function exposed to Gd-based contrast agents. / Delfino, Riccarda; Biasotto, Matteo; Candido, Riccardo; Altissimo, Matteo; Stebel, Marco; Salomè, Murielle; van Elteren, Johannes T.; Vogel Mikuš, Katarina; Zennaro, Cristina; Šala, Martin; Addobbati, Riccardo; Tromba, Giuliana; Pascolo, Lorella.

In: Toxicology Letters, Vol. 301, 01.02.2019, p. 157-167.

Research output: Contribution to journalArticle

Delfino, R, Biasotto, M, Candido, R, Altissimo, M, Stebel, M, Salomè, M, van Elteren, JT, Vogel Mikuš, K, Zennaro, C, Šala, M, Addobbati, R, Tromba, G & Pascolo, L 2019, 'Gadolinium tissue deposition in the periodontal ligament of mice with reduced renal function exposed to Gd-based contrast agents', Toxicology Letters, vol. 301, pp. 157-167. https://doi.org/10.1016/j.toxlet.2018.11.014
Delfino, Riccarda ; Biasotto, Matteo ; Candido, Riccardo ; Altissimo, Matteo ; Stebel, Marco ; Salomè, Murielle ; van Elteren, Johannes T. ; Vogel Mikuš, Katarina ; Zennaro, Cristina ; Šala, Martin ; Addobbati, Riccardo ; Tromba, Giuliana ; Pascolo, Lorella. / Gadolinium tissue deposition in the periodontal ligament of mice with reduced renal function exposed to Gd-based contrast agents. In: Toxicology Letters. 2019 ; Vol. 301. pp. 157-167.
@article{5aff9306fb204717b69f90ef0feed554,
title = "Gadolinium tissue deposition in the periodontal ligament of mice with reduced renal function exposed to Gd-based contrast agents",
abstract = "Gadolinium deposition in tissue is linked to nephrogenic systemic fibrosis (NSF): a rare disorder occurring in patients with severe chronic kidney disease and associated with administration of Gd-based contrast agents (GBCAs) for Magnetic Resonance Imaging (MRI). It is suggested that the GBCAs prolonged permanence in blood in these patients may result in a Gd precipitation in peripheral or central organs, where it initiates a fibrotic process. In this study we investigated new sites of retention/precipitation of Gd in a mouse model of renal disease (5/6 nephrectomy) receiving two doses (closely after each other) of a linear GBCA. Two commercial GBCAs (Omniscan{\circledR} and Magnevist{\circledR}) were administered at doses slightly higher than those used in clinical practice (0.7 mmol/kg body weight, each). The animals were sacrificed one month after the last administration and the explanted organs (kidney, liver, femur, dorsal skin, teeth) were analysed by X-ray fluorescence (XRF) at two synchrotron facilities. The XRF analysis with a millimetre-sized beam at the SYRMEP beamline (Elettra, Italy) produced no detectable levels of Gd in the examined tissues, with the notable exception of the incisors of the nephrectomised mice. The XRF analyses at sub-micron resolution performed at ID21 (ESRF, France) allowed to clearly localize Gd in the periodontal ligaments of teeth both from Omniscan{\circledR} and Magnevist{\circledR} treated nephrectomised mice. The latter results were further confirmed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The study prompts that prolonged permanence of GBCAs in blood may result in Gd retention in this particular muscular tissue, opening possibilities for diagnostic applications at this level when investigating Gd-related toxicities.",
keywords = "5/6 nephrectomy, Gadolinium, GBCAs, MRI contrast agent, Periodontal ligament, XRF",
author = "Riccarda Delfino and Matteo Biasotto and Riccardo Candido and Matteo Altissimo and Marco Stebel and Murielle Salom{\`e} and {van Elteren}, {Johannes T.} and {Vogel Mikuš}, Katarina and Cristina Zennaro and Martin Šala and Riccardo Addobbati and Giuliana Tromba and Lorella Pascolo",
year = "2019",
month = "2",
day = "1",
doi = "10.1016/j.toxlet.2018.11.014",
language = "English",
volume = "301",
pages = "157--167",
journal = "Toxicology Letters",
issn = "0378-4274",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Gadolinium tissue deposition in the periodontal ligament of mice with reduced renal function exposed to Gd-based contrast agents

AU - Delfino, Riccarda

AU - Biasotto, Matteo

AU - Candido, Riccardo

AU - Altissimo, Matteo

AU - Stebel, Marco

AU - Salomè, Murielle

AU - van Elteren, Johannes T.

AU - Vogel Mikuš, Katarina

AU - Zennaro, Cristina

AU - Šala, Martin

AU - Addobbati, Riccardo

AU - Tromba, Giuliana

AU - Pascolo, Lorella

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Gadolinium deposition in tissue is linked to nephrogenic systemic fibrosis (NSF): a rare disorder occurring in patients with severe chronic kidney disease and associated with administration of Gd-based contrast agents (GBCAs) for Magnetic Resonance Imaging (MRI). It is suggested that the GBCAs prolonged permanence in blood in these patients may result in a Gd precipitation in peripheral or central organs, where it initiates a fibrotic process. In this study we investigated new sites of retention/precipitation of Gd in a mouse model of renal disease (5/6 nephrectomy) receiving two doses (closely after each other) of a linear GBCA. Two commercial GBCAs (Omniscan® and Magnevist®) were administered at doses slightly higher than those used in clinical practice (0.7 mmol/kg body weight, each). The animals were sacrificed one month after the last administration and the explanted organs (kidney, liver, femur, dorsal skin, teeth) were analysed by X-ray fluorescence (XRF) at two synchrotron facilities. The XRF analysis with a millimetre-sized beam at the SYRMEP beamline (Elettra, Italy) produced no detectable levels of Gd in the examined tissues, with the notable exception of the incisors of the nephrectomised mice. The XRF analyses at sub-micron resolution performed at ID21 (ESRF, France) allowed to clearly localize Gd in the periodontal ligaments of teeth both from Omniscan® and Magnevist® treated nephrectomised mice. The latter results were further confirmed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The study prompts that prolonged permanence of GBCAs in blood may result in Gd retention in this particular muscular tissue, opening possibilities for diagnostic applications at this level when investigating Gd-related toxicities.

AB - Gadolinium deposition in tissue is linked to nephrogenic systemic fibrosis (NSF): a rare disorder occurring in patients with severe chronic kidney disease and associated with administration of Gd-based contrast agents (GBCAs) for Magnetic Resonance Imaging (MRI). It is suggested that the GBCAs prolonged permanence in blood in these patients may result in a Gd precipitation in peripheral or central organs, where it initiates a fibrotic process. In this study we investigated new sites of retention/precipitation of Gd in a mouse model of renal disease (5/6 nephrectomy) receiving two doses (closely after each other) of a linear GBCA. Two commercial GBCAs (Omniscan® and Magnevist®) were administered at doses slightly higher than those used in clinical practice (0.7 mmol/kg body weight, each). The animals were sacrificed one month after the last administration and the explanted organs (kidney, liver, femur, dorsal skin, teeth) were analysed by X-ray fluorescence (XRF) at two synchrotron facilities. The XRF analysis with a millimetre-sized beam at the SYRMEP beamline (Elettra, Italy) produced no detectable levels of Gd in the examined tissues, with the notable exception of the incisors of the nephrectomised mice. The XRF analyses at sub-micron resolution performed at ID21 (ESRF, France) allowed to clearly localize Gd in the periodontal ligaments of teeth both from Omniscan® and Magnevist® treated nephrectomised mice. The latter results were further confirmed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The study prompts that prolonged permanence of GBCAs in blood may result in Gd retention in this particular muscular tissue, opening possibilities for diagnostic applications at this level when investigating Gd-related toxicities.

KW - 5/6 nephrectomy

KW - Gadolinium

KW - GBCAs

KW - MRI contrast agent

KW - Periodontal ligament

KW - XRF

UR - http://www.scopus.com/inward/record.url?scp=85057478686&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85057478686&partnerID=8YFLogxK

U2 - 10.1016/j.toxlet.2018.11.014

DO - 10.1016/j.toxlet.2018.11.014

M3 - Article

C2 - 30476537

AN - SCOPUS:85057478686

VL - 301

SP - 157

EP - 167

JO - Toxicology Letters

JF - Toxicology Letters

SN - 0378-4274

ER -