Gadolinium and gadoteric acid exposure induce long-term down-regulation in erythroid-related genes

Authors

  • Susana Coimbra UCIBIO—Applied Molecular Biosciences Unit, Department of Biological Sciences, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; 1H-TOXRUN—One Health Toxicology Research Unit, University Institute of Health Sciences, CESPU, CRL, Gandra, Portugal https://orcid.org/0000-0001-8411-8038
  • Susana Rocha UCIBIO—Applied Molecular Biosciences Unit, Department of Biological Sciences, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
  • Sofia D. Viana Institute of Pharmacology & Experimental Therapeutics, & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra; Polytechnic Institute of Coimbra, ESTESC-Coimbra Health School, Pharmacy, Coimbra, Portugal
  • Rute Rebelo UCIBIO—Applied Molecular Biosciences Unit, Department of Biological Sciences, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
  • Petronila Rocha-Pereira UCIBIO—Applied Molecular Biosciences Unit, Department of Biological Sciences, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; Health Science Research Centre, University of Beira Interior, Covilhã, Portugal
  • Maria João Valente National Food Institute, Technical University of Denmark, Kgs Lyngby, Denmark
  • Cristina Catarino UCIBIO—Applied Molecular Biosciences Unit, Department of Biological Sciences, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
  • Elsa Bronze-da-Rocha UCIBIO—Applied Molecular Biosciences Unit, Department of Biological Sciences, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
  • Luís Belo UCIBIO—Applied Molecular Biosciences Unit, Department of Biological Sciences, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
  • Flávio Reis Institute of Pharmacology & Experimental Therapeutics, & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra
  • Alice Santos-Silva UCIBIO—Applied Molecular Biosciences Unit, Department of Biological Sciences, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal

DOI:

https://doi.org/10.48797/sl.2024.227

Keywords:

Poster

Abstract

Background: Gadolinium-based contrast agents (GBCA) differ in their potential to release gadolinium [Gd (III)], known to be toxic. Gadoteric acid (Gd-DOTA) is a macrocyclic GBCA, with a more stable structure. After GBCA exposure, Gd (III) retention in red blood cells (RBC) and kidney has been reported [1,2]. Nephrogenic systemic fibrosis, a severe condition found in renal disease patients exposed to GBCA, is associated with decreased hemoglobin (Hb) levels [3]. Objective: To evaluate the long-term effects of Gd (III) and Gd-DOTA exposure on erythropoietic function, using an animal model. Methods: In a long-term study (20 weeks after exposure), male Wistar rats were divided in 3 groups (n=10 each): exposure to a single dose (0.1 mmol/kg) of Gd (III), of Gd-DOTA or vehicle (control). At the end of the protocol, blood and renal tissue were collected; erythrogram was determined, and next-generation sequencing analysis was employed to evaluate differential gene expression of kidney tissue transcriptome. Results: Gd (III) group presented significantly lower RBC and hematocrit values, and higher mean cell hemoglobin concentration (MCHC) and a trend towards lower Hb levels; Gd-DOTA group presented trends to similar changes, without reaching statistical significance. In both groups, down-regulation of HBA1 (encodes Hb subunit alpha 1), HBB(encodes Hb subunit beta) and SLC4A1 (encodes band 3, a transmembrane chloride/bicarbonate anion exchanger1, found in RBC and kidney) genes was observed. Conclusions: Single exposure to free Gd (III) induced long-term down-regulation in erythroid-related genes that may underly erythropoietic and erythrocyte disturbances, as suggested by less RBC and increased MCHC. Although only alteration tendencies in these biomarkers were observed, exposure to Gd-DOTA showed the same genes downregulation. Further studies are necessary to confirm gene expression data through qPCR, to better understand the interplay between Gd (III) and erythropoiesis, and to evaluate Gd-DOTA safety.

References

1. Richter, H., Bucker, P., Martin, L.F., Dunker, C., Fingerhut, S., Xia, A., Karol, A., Sperling, M., Karst, U., Radbruch, A., Jeibmann, A. Gadolinium Tissue Distribution in a Large-Animal Model after a Single Dose of Gadolinium-based Contrast Agents. Radiology (2021), 301, 637-642.

2. Di Gregorio, E., Furlan, C., Atlante, S., Stefania, R., Gianolio, E., Aime, S. Gadolinium Retention in Erythrocytes and Leukocytes From Human and Murine Blood Upon Treatment With Gadolinium-Based Contrast Agents for Magnetic Resonance Imaging. Invest Radiol (2020), 55, 30-37.

3. Wiginton, C.D., Kelly, B., Oto, A., Jesse, M., Aristimuno, P., Ernst, R., Chaljub, G. Gadolinium-Based Contrast Exposure, Nephrogenic Systemic Fibrosis, and Gadolinium Detection in Tissue. Am J Roentgenol (2008), 190, 1060-1068.

Downloads

Published

2024-05-01

How to Cite

Coimbra, S., Rocha, S., D. Viana, S., Rebelo, R., Rocha-Pereira, P., Valente, M. J., Catarino, C., Bronze-da-Rocha, E., Belo, L., Reis, F., & Santos-Silva, A. (2024). Gadolinium and gadoteric acid exposure induce long-term down-regulation in erythroid-related genes. Scientific Letters, 1(Sup 1). https://doi.org/10.48797/sl.2024.227

Issue

Section

Posters

Most read articles by the same author(s)

Similar Articles

<< < 3 4 5 6 7 8 9 10 11 12 > >> 

You may also start an advanced similarity search for this article.