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Nephrotoxicity of iopamidol is associated with mitochondrial impairment in human cell and teleost models

Iopamidol is a nonionic, low-osmolar iodinated contrast agent used for angiography. Its clinical use is associated with renal dysfunction. Patients suffering from preexisting kidney disease have an increased risk of renal failure upon iopamidol administration. Studies in animals confirmed renal toxi...

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Main Authors: Bolten, Jan Stephan (Author) , Mancuso, Riccardo Vincenzo (Author) , Roos, Noëmi Johanna (Author) , Mayr, Aline (Author) , Puligilla, Ramya Deepthi (Author) , Kraus, Lisa (Author) , Odermatt, Alex (Author) , Fricker, Gert (Author) , Huwyler, Jörg (Author)
Format: Article (Journal)
Language:English
Published: 28 March 2023
In: Toxicology and applied pharmacology
Year: 2023, Volume: 466, Pages: 1-14
ISSN:1096-0333
DOI:10.1016/j.taap.2023.116493
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.taap.2023.116493
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0041008X2300131X
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Author Notes:Jan Stephan Bolten, Riccardo Vincenzo Mancuso, Noëmi Johanna Roos, Aline Mayr, Ramya Deepthi Puligilla, Lisa Kraus, Alex Odermatt, Gert Fricker, Jörg Huwyler
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Summary:Iopamidol is a nonionic, low-osmolar iodinated contrast agent used for angiography. Its clinical use is associated with renal dysfunction. Patients suffering from preexisting kidney disease have an increased risk of renal failure upon iopamidol administration. Studies in animals confirmed renal toxicity, but the involved mechanisms remain unclear. Therefore, the aim of the present study was to use human embryonic kidney cells (HEK293T) as a general cell model of mitochondrial damage, as well as, zebrafish larvae, and isolated proximal tubules of killifish to investigate factors promoting renal tubular toxicity of iopamidol with a focus on mitochondrial damage. Results from in vitro HEK293T cell-based assays indicate that iopamidol affects mitochondrial function Treatment with iopamidol induces ATP depletion, reduces the mitochondrial membrane potential, and elevates mitochondrial superoxide and reactive oxygen species accumulation. Similar results were obtained with gentamicin sulfate and cadmium chloride, two well-known model compounds associated with renal tubular toxicity. Confocal microscopy confirms changes in mitochondrial morphology, such as mitochondrial fission. Importantly, these results were confirmed in proximal renal tubular epithelial cells using ex vivo and in vivo teleost models. In conclusion, this study provides evidence for iopamidol-induced mitochondrial damage in proximal renal epithelial cells. Teleost models allow studying proximal tubular toxicity with translational relevance for humans.
Item Description:Online verfügbar 26. März 2023, Artikelversion 28. März 2023
Gesehen am 17.05.2023
Physical Description:Online Resource
ISSN:1096-0333
DOI:10.1016/j.taap.2023.116493

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