{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T18:16:38Z","timestamp":1766600198114,"version":"build-2065373602"},"reference-count":58,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT","award":["2022.08400.PTDC"],"award-info":[{"award-number":["2022.08400.PTDC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoX"],"abstract":"<jats:p>Regarding the safety of gadolinium (Gd (III))-based contrast agents, we aimed to evaluate the short- and long-term effects following a single exposure to gadoteric acid (DOTA) or to free Gd (III) using animal models. Biomarkers of kidney injury, inflammation, iron metabolism, dyslipidemia, hepatic and hematologic disturbances and kidney histopathological and differential gene expression (DGE) analyses were evaluated. In the short-term study, compared to the controls, exposure to Gd (III) was associated with higher inflammation; changes in lipid, iron and hepatic metabolisms; hematological alterations; and kidney damage. Exposure to DOTA revealed changes in hematological, lipid and hepatic biomarkers. In the long-term study, compared to the controls, exposure to Gd (III) or to DOTA showed much fewer changes than the short-term exposure. Comparing the kidney gene expression of Gd (III) or DOTA exposure versus the control, we found clearly different DGE patterns and a lower number of differently expressed genes in the long-term study, for both compounds. Our data show that a single-dose exposure to these compounds induces several short-term changes which over time return to normal or are sustained, although with less severity, especially in the case of DOTA.<\/jats:p>","DOI":"10.3390\/jox15020034","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T07:53:06Z","timestamp":1740124386000},"page":"34","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Gadoteric Acid and Gadolinium: Exploring Short- and Long-Term Effects on Healthy Animals"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8411-8038","authenticated-orcid":false,"given":"Susana","family":"Coimbra","sequence":"first","affiliation":[{"name":"UCIBIO i4HB, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO i4HB, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), Avenida Central de Gandra 1317, 4585-116 Gandra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4196-2217","authenticated-orcid":false,"given":"Susana","family":"Rocha","sequence":"additional","affiliation":[{"name":"UCIBIO i4HB, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1316-1319","authenticated-orcid":false,"given":"Sofia D.","family":"Viana","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology & Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"ESTESC-Coimbra Health School, Polytechnic Institute of Coimbra, 3046-854 Coimbra, Portugal"},{"name":"H&TRC-Health and Technology Research Center, Coimbra Health School, Polytechnic University of Coimbra, 3046-854 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9185-6282","authenticated-orcid":false,"given":"Rute","family":"Rebelo","sequence":"additional","affiliation":[{"name":"UCIBIO i4HB, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Petronila","family":"Rocha-Pereira","sequence":"additional","affiliation":[{"name":"UCIBIO i4HB, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"Health Science Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8257-5841","authenticated-orcid":false,"given":"Irina","family":"Lousa","sequence":"additional","affiliation":[{"name":"UCIBIO i4HB, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Maria Jo\u00e3o","family":"Valente","sequence":"additional","affiliation":[{"name":"National Food Institute, Technical University of Denmark, 2800 Kgs Lyngby, Denmark"}]},{"given":"Cristina","family":"Catarino","sequence":"additional","affiliation":[{"name":"UCIBIO i4HB, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3941-6850","authenticated-orcid":false,"given":"Lu\u00eds","family":"Belo","sequence":"additional","affiliation":[{"name":"UCIBIO i4HB, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3571-2513","authenticated-orcid":false,"given":"Elsa","family":"Bronze-da-Rocha","sequence":"additional","affiliation":[{"name":"UCIBIO i4HB, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3401-9554","authenticated-orcid":false,"given":"Fl\u00e1vio","family":"Reis","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology & Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2565-3169","authenticated-orcid":false,"given":"Alice","family":"Santos-Silva","sequence":"additional","affiliation":[{"name":"UCIBIO i4HB, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Martino, F., Amici, G., Rosner, M., Ronco, C., and Novara, G. (2021). Gadolinium-Based Contrast Media Nephrotoxicity in Kidney Impairment: The Physio-Pathological Conditions for the Perfect Murder. J. Clin. Med., 10.","DOI":"10.3390\/jcm10020271"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1093\/ndt\/gfk062","article-title":"Gadolinium\u2014A specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis?","volume":"21","author":"Grobner","year":"2006","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1056\/NEJMcpc0708697","article-title":"Case records of the Massachusetts General Hospital. Case 6-2008. A 46-year-old woman with renal failure and stiffness of the joints and skin","volume":"358","author":"Kay","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.ejrad.2008.02.011","article-title":"Nephrogenic systemic fibrosis associated with gadolinium based contrast agents: A summary of the medical literature reporting","volume":"66","author":"Broome","year":"2008","journal-title":"Eur. J. Radiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1111\/j.1365-2133.2011.10465.x","article-title":"Nephrogenic systemic fibrosis is found only among gadolinium-exposed patients with renal insufficiency: A case-control study from Denmark","volume":"165","author":"Elmholdt","year":"2011","journal-title":"Br. J. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"747","DOI":"10.2215\/CJN.05721207","article-title":"Risk for nephrogenic systemic fibrosis with gadoteridol (ProHance) in patients who are on long-term hemodialysis","volume":"3","author":"Reilly","year":"2008","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_7","first-page":"285","article-title":"Two cases of nephrogenic systemic fibrosis after exposure to the macrocyclic compound gadobutrol","volume":"3","author":"Elmholdt","year":"2010","journal-title":"NDT Plus"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3882","DOI":"10.1093\/ndt\/gfp494","article-title":"NSF after Gadovist exposure: A case report and hypothesis of NSF development","volume":"24","author":"Wollanka","year":"2009","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1002\/mrm.28060","article-title":"Analysis of retention of gadolinium by brain, bone, and blood following linear gadolinium-based contrast agent administration in rats with experimental sepsis","volume":"83","author":"Damme","year":"2020","journal-title":"Magn. Reson. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"F844","DOI":"10.1152\/ajprenal.00379.2014","article-title":"Type of MRI contrast, tissue gadolinium, and fibrosis","volume":"307","author":"Do","year":"2014","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1148\/radiol.13131669","article-title":"High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: Relationship with increasing cumulative dose of a gadolinium-based contrast material","volume":"270","author":"Kanda","year":"2014","journal-title":"Radiology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1002\/jmri.26031","article-title":"Effects of gadolinium-based MRI contrast agents on liver tissue","volume":"48","author":"Mercantepe","year":"2018","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s10534-016-9931-7","article-title":"Gadolinium-based contrast agent toxicity: A review of known and proposed mechanisms","volume":"29","author":"Rogosnitzky","year":"2016","journal-title":"Biometals"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"102291","DOI":"10.1016\/j.jksus.2022.102291","article-title":"Immunotoxic potential of nanoparticles of cerium oxide and gadolinium oxide in human monocyte (THP-1) cells","volume":"34","author":"Akhtar","year":"2022","journal-title":"J. King Saud. Univ.\u2013Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"147256","DOI":"10.1016\/j.brainres.2020.147256","article-title":"Repeated gadoteric acid and gadobutrol exposure causes deterioration of behavior and memory functions in rats: MRI, histopathological and biochemical evidence","volume":"1754","author":"Solmaz","year":"2021","journal-title":"Brain Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.taap.2019.05.009","article-title":"Gadolinium-based contrast agents: Stimulators of myeloid-induced renal fibrosis and major metabolic disruptors","volume":"375","author":"Do","year":"2019","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3535769","DOI":"10.1155\/2018\/3535769","article-title":"Exposure of Macrophages to Low-Dose Gadolinium-Based Contrast Medium: Impact on Oxidative Stress and Cytokines Production","volume":"2018","author":"Weng","year":"2018","journal-title":"Contrast Media Mol. Imaging"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Pereira, L.V., Shimizu, M.H., Rodrigues, L.P., Leite, C.C., Andrade, L., and Seguro, A.C. (2012). N-acetylcysteine protects rats with chronic renal failure from gadolinium-chelate nephrotoxicity. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039528"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1093\/toxsci\/kfab148","article-title":"Cellular and Molecular Pathways Underlying the Nephrotoxicity of Gadolinium","volume":"186","author":"Rocha","year":"2022","journal-title":"Toxicol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13244-019-0824-5","article-title":"Macrocyclic MR contrast agents: Evaluation of multiple-organ gadolinium retention in healthy rats","volume":"11","author":"Bussi","year":"2020","journal-title":"Insights Imaging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1097\/RLI.0000000000000252","article-title":"Macrocyclic and Other Non-Group 1 Gadolinium Contrast Agents Deposit Low Levels of Gadolinium in Brain and Bone Tissue: Preliminary Results From 9 Patients With Normal Renal Function","volume":"51","author":"Murata","year":"2016","journal-title":"Investig. Radiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kobayashi, A., Hirano, K., Okuda, T., Ikenoue, T., Yokoo, T., and Fukuma, S. (2024). Estimating the prevalence of chronic kidney disease in the older population using health screening data in Japan. Clin. Exp. Nephrol.","DOI":"10.1007\/s10157-024-02570-y"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s42826-024-00194-7","article-title":"Age-related changes in hematological and biochemical profiles of Wistar rats","volume":"40","author":"Patel","year":"2024","journal-title":"Lab. Anim. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1515\/BC.2007.061","article-title":"Clinical chemistry reference database for Wistar rats and C57\/BL6 mice","volume":"388","author":"Boehm","year":"2007","journal-title":"Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"He, Q., Su, G., Liu, K., Zhang, F., Jiang, Y., Gao, J., Liu, L., Jiang, Z., Jin, M., and Xie, H. (2017). Sex-specific reference intervals of hematologic and biochemical analytes in Sprague-Dawley rats using the nonparametric rank percentile method. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0189837"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1080\/13685538.2017.1350156","article-title":"Reference database of hematological parameters for growing and aging rats","volume":"21","author":"Lima","year":"2018","journal-title":"Aging Male"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1111\/j.1939-165X.2012.00427.x","article-title":"Differences in hematologic variables in rats of the same strain but different origin","volume":"41","author":"Kampfmann","year":"2012","journal-title":"Vet. Clin. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"259","DOI":"10.15312\/EurasianJVetSci.2021.351","article-title":"Biochemical and hematological profiles of wistar rats at the Selcuk University experimental medicine research and application center","volume":"37","author":"Ecer","year":"2021","journal-title":"Eurasian J. Vet. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1515\/labmed-2018-0500","article-title":"Determination and verification of reference interval limits in clinical chemistry. Recommendations for laboratories on behalf of the Working Group Guide Limits of the DGKL with respect to ISO Standard 15189 and the Guideline of the German Medical Association on Quality Assurance in Medical Laboratory Examinations (Rili-BAEK)","volume":"43","author":"Haeckel","year":"2019","journal-title":"J. Lab. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Timbrell, N.E. (2024). The Role and Limitations of the Reference Interval Within Clinical Chemistry and Its Reliability for Disease Detection. Br. J. Biomed. Sci., 81.","DOI":"10.3389\/bjbs.2024.12339"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"155416","DOI":"10.1016\/j.scitotenv.2022.155416","article-title":"Inflammation and accompanied disrupted hematopoiesis in adult mouse induced by rare earth element nanoparticles","volume":"831","author":"Gao","year":"2022","journal-title":"Sci. Total Environ."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.etp.2008.11.004","article-title":"The involvement of pro-inflammatory cytokines in nephrogenic systemic fibrosis\u2014A mechanistic hypothesis based on preclinical results from a rat model treated with gadodiamide","volume":"61","author":"Raschke","year":"2009","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"12425","DOI":"10.1021\/acsnano.5b05783","article-title":"Parallel Comparative Studies on Mouse Toxicity of Oxide Nanoparticle- and Gadolinium-Based T1 MRI Contrast Agents","volume":"9","author":"Chen","year":"2015","journal-title":"ACS Nano"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s10517-006-0373-z","article-title":"Intralysosomal accumulation of gadolinium and lysosomal damage during selective depression of liver macrophages in vivo","volume":"142","author":"Korolenko","year":"2006","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1038\/labinvest.2009.92","article-title":"Phagocytosis of gadolinium chloride or zymosan induces simultaneous upregulation of hepcidin- and downregulation of hemojuvelin- and Fpn-1-gene expression in murine liver","volume":"89","author":"Moriconi","year":"2009","journal-title":"Lab. Investig."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wang, J., Erlacher, M., and Fernandez-Orth, J. (2022). The role of inflammation in hematopoiesis and bone marrow failure: What can we learn from mouse models?. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.951937"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Coimbra, S., Rocha, S., Sousa, N.R., Catarino, C., Belo, L., Bronze-da-Rocha, E., Valente, M.J., and Santos-Silva, A. (2024). Toxicity Mechanisms of Gadolinium and Gadolinium-Based Contrast Agents-A Review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25074071"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/S1002-0721(08)60234-3","article-title":"Biochemical effects of gadolinium chloride in rats liver and kidney studied by 1H NMR metabolomics","volume":"27","author":"Liao","year":"2009","journal-title":"J. Rare Earths"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s10534-011-9419-4","article-title":"Metabolomic profiles delineate potential roles for gadolinium chloride in the proliferation or inhibition of Hela cells","volume":"24","author":"Long","year":"2011","journal-title":"Biometals"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1016\/j.jid.2019.03.1145","article-title":"Nephrogenic Systemic Fibrosis Is Mediated by Myeloid C-C Chemokine Receptor 2","volume":"139","author":"Do","year":"2019","journal-title":"J. Investig. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lousa, I., Reis, F., Viana, S., Vieira, P., Vala, H., Belo, L., and Santos-Silva, A. (2023). TNFR2 as a Potential Biomarker for Early Detection and Progression of CKD. Biomolecules, 13.","DOI":"10.3390\/biom13030534"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/icb.2014.121","article-title":"Cystatin C is a disease-associated protein subject to multiple regulation","volume":"93","author":"Xu","year":"2015","journal-title":"Immunol. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1097\/RLI.0b013e3181e943d2","article-title":"Fibroblast response to gadolinium: Role for platelet-derived growth factor receptor","volume":"45","author":"Bhagavathula","year":"2010","journal-title":"Investig. Radiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/S0024-3205(02)02342-1","article-title":"Gadolinium chloride reverses dimethylnitrosamine (DMN)-induced rat liver fibrosis with increased matrix metalloproteinases (MMPs) of Kupffer cells","volume":"72","author":"Sakaida","year":"2003","journal-title":"Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/978-1-4757-9613-1_41","article-title":"Liver cysteine proteinases in macrophage depression induced by gadolinium chloride","volume":"421","author":"Korolenko","year":"1997","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1097\/RLI.0000000000000423","article-title":"The Issue of Gadolinium Retained in Tissues: Insights on the Role of Metal Complex Stability by Comparing Metal Uptake in Murine Tissues Upon the Concomitant Administration of Lanthanum- and Gadolinium-Diethylentriamminopentaacetate","volume":"53","author":"Ferrauto","year":"2018","journal-title":"Investig. Radiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1124\/dmd.118.082958","article-title":"Emerging Kidney Models to Investigate Metabolism, Transport, and Toxicity of Drugs and Xenobiotics","volume":"46","author":"Bajaj","year":"2018","journal-title":"Drug Metab. Dispos."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.toxlet.2021.07.016","article-title":"Potential toxicity evaluation and comparison within multiple mice organs after repeat injections of linear versus macrocyclic gadolinium-based contrast agents: A comprehensive and time course study","volume":"350","author":"Kong","year":"2021","journal-title":"Toxicol. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s00775-011-0757-z","article-title":"Gadolinium exposure disrupts iron homeostasis in cultured cells","volume":"16","author":"Ghio","year":"2011","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1111\/obr.12057","article-title":"The role of adipocytes in the modulation of iron metabolism in obesity","volume":"14","author":"Coimbra","year":"2013","journal-title":"Obes. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5567","DOI":"10.1039\/C9NA00567F","article-title":"Formation of gadolinium-ferritin from clinical magnetic resonance contrast agents","volume":"2","author":"Neburkova","year":"2020","journal-title":"Nanoscale Adv."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.7150\/thno.93856","article-title":"H-ferritin-nanocaged gadolinium nanoparticles for ultra-sensitive MR molecular imaging","volume":"14","author":"Zhang","year":"2024","journal-title":"Theranostics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1093\/jn\/130.9.2378","article-title":"Iron status and stores decline with age in Lewis rats","volume":"130","author":"Ahluwalia","year":"2000","journal-title":"J. Nutr."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Richter, H., Koke, A., Soschinski, P.N., Martin, L.F., Bucker, P., Sperling, M., Karst, U., Radbruch, A., Witten, A., and Jeibmann, A. (2023). Elemental bioimaging and transcriptomics reveal unchanged gene expression in mouse cerebellum following a single injection of Gadolinium-based contrast agents. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-33066-6"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1002\/jmri.26266","article-title":"Effects of Gadodiamide and Gadoteric Acid on Rat Kidneys: A Comparative Study","volume":"49","author":"Celiker","year":"2019","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1002\/jmri.27693","article-title":"Gadolinium Clearance in the First 5 Weeks After Repeated Intravenous Administration of Gadoteridol, Gadoterate Meglumine, and Gadobutrol to rats","volume":"54","author":"Bussi","year":"2021","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1002\/jmri.25822","article-title":"Differences in gadolinium retention after repeated injections of macrocyclic MR contrast agents to rats","volume":"47","author":"Bussi","year":"2018","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Percie du Sert, N., Hurst, V., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., and Dirnagl, U. (2020). The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. BMC Vet. Res., 16.","DOI":"10.1186\/s12917-020-02451-y"}],"container-title":["Journal of Xenobiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2039-4713\/15\/2\/34\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:39:48Z","timestamp":1760027988000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2039-4713\/15\/2\/34"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,21]]},"references-count":58,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["jox15020034"],"URL":"https:\/\/doi.org\/10.3390\/jox15020034","relation":{},"ISSN":["2039-4713"],"issn-type":[{"type":"electronic","value":"2039-4713"}],"subject":[],"published":{"date-parts":[[2025,2,21]]}}}