Short-term and long-term effects of gadolinium and gadoteric acid exposure on rat kidney and liver functions
DOI:
https://doi.org/10.48797/sl.2024.229Keywords:
PosterAbstract
Background: There are currently concerns about the safety of gadolinium-based contrast agents (GBCA), as they can release gadolinium [Gd (III)], known to be toxic. Free Gd (III) deposition at different organs, as kidney and liver, has been reported [1,2]. We found that Gd (III) promotes inflammation and fibrosis in proximal tubular cells [3]. GBCA with macrocyclic structure, as gadoteric acid (Gd-DOTA), are considered more stable. Objective: To evaluate the short-term and the long-term effects of Gd (III) and Gd-DOTA exposure on biomarkers of renal and hepatic functions, using an animal model. Methods: In both short-term (48h) and long-term (20 weeks) studies, eight weeks-old male Wistar rats were divided in 3 groups (n=10 each) exposed to: a single dose (0.1 mmol/kg) of Gd (III), of Gd-DOTA (0.1 mmol/kg) or vehicle (control). At the end of protocols, blood was collected and the levels of creatinine, urea, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were evaluated using routine automated assays; cystatin C was measured by ELISA. Results: In the short-term study (48h), Gd (III) group presented significantly higher values of AST and ALT, and lower urea levels than the control group; Gd-DOTA group presented higher AST values, compared to the control group. Twenty-weeks after exposure, higher values of AST, ALT, and creatinine, than Gd-DOTA and control groups and, lower cystatin levels, compared to the control group, were found for the Gd (III) group. Conclusions: Single exposure to free Gd (III) induced short-term and long-term changes in liver biomarkers; the exposure to Gd-DOTA was associated with fewer short-term disturbances in transaminases, and with no long-term influence in their values. Exposure to Gd-DOTA had little influence in traditional kidney biomarkers. Despite the significantly safer profile for Gd-DOTA, further studies are necessary, testing other biomarkers, to clarify the short-term and the long-term impact of this GBCA.
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. Mercantepe, T., Tumkaya, L., Celiker, F.B., Topal Suzan, Z., Cinar, S., Akyildiz, K., Mercantepe, F., Yilmaz, A. Effects of gadolinium-based MRI contrast agents on liver tissue. J Magn Reson Imaging (2018), 48, 1367-1374.
3. Sousa, N.R., Rocha, S., Santos-Silva, A., Coimbra, S., Valente, M.J. Cellular and molecular pathways underlying the nephrotoxicity of gadolinium. Toxicol Sci. (2022), 186, 134-148.
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Copyright (c) 2024 Susana Coimbra, Susana Rocha, Sofia D. Viana, Rute Rebelo, Petronila Rocha-Pereira, Maria João Valente, Cristina Catarino, Elsa Bronze-da-Rocha, Luís Belo, Flávio Reis, Alice Santos-Silva
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