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Zebrafish (Danio rerio) larvae as a predictive model to study gentamicin-induced structural alterations of the kidney
Nephrotoxicity is an important drug safety aspect to be assessed during drug discovery and development. To study renal toxicity, in vitro cell-based assays are often used. Unfortunately, translating the results of such cell assays to vertebrates including human remains challenging. Therefore, we aim...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10118166/ https://www.ncbi.nlm.nih.gov/pubmed/37079551 http://dx.doi.org/10.1371/journal.pone.0284562 |
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author | Bolten, Jan Stephan Tanner, Christine Rodgers, Griffin Schulz, Georg Levano, Soledad Weitkamp, Timm Waldner, Samuel Puligilla, Ramya Deepthi Bodmer, Daniel Müller, Bert Huwyler, Jörg |
author_facet | Bolten, Jan Stephan Tanner, Christine Rodgers, Griffin Schulz, Georg Levano, Soledad Weitkamp, Timm Waldner, Samuel Puligilla, Ramya Deepthi Bodmer, Daniel Müller, Bert Huwyler, Jörg |
author_sort | Bolten, Jan Stephan |
collection | PubMed |
description | Nephrotoxicity is an important drug safety aspect to be assessed during drug discovery and development. To study renal toxicity, in vitro cell-based assays are often used. Unfortunately, translating the results of such cell assays to vertebrates including human remains challenging. Therefore, we aim to evaluate whether zebrafish larvae (ZFL) could serve as a vertebrate screening model to detect gentamicin-induced changes of kidney glomeruli and proximal tubules. To validate the model, we compared the results of ZFL with those obtained from kidney biopsies of gentamicin-treated mice. We used transgenic zebrafish lines expressing enhanced green fluorescent proteins in the glomerulus to visualize glomerular damage. Synchrotron radiation-based computed tomography (SRμCT) is a label-free approach providing three-dimensional representations of renal structures with micrometre resolution. Clinically used gentamicin concentrations induce nephrotoxicity and affect glomerular and proximal tubular morphology. Findings were confirmed in mice and ZFL. There was a strong correlation between fluorescent signals in ZFL, SRμCT- derived descriptors of glomerular and proximal tubular morphology and the histological analysis of mouse kidney biopsies. A combination of SRμCT and confocal microscopy provides unprecedented insights into anatomical structures of the zebrafish kidney. Based on our findings, we suggest to use ZFL as a predictive vertebrate screening model to study drug-induced nephrotoxicity and to bridge the gap between cell culture-based test systems and experiments in mammals. |
format | Online Article Text |
id | pubmed-10118166 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-101181662023-04-21 Zebrafish (Danio rerio) larvae as a predictive model to study gentamicin-induced structural alterations of the kidney Bolten, Jan Stephan Tanner, Christine Rodgers, Griffin Schulz, Georg Levano, Soledad Weitkamp, Timm Waldner, Samuel Puligilla, Ramya Deepthi Bodmer, Daniel Müller, Bert Huwyler, Jörg PLoS One Research Article Nephrotoxicity is an important drug safety aspect to be assessed during drug discovery and development. To study renal toxicity, in vitro cell-based assays are often used. Unfortunately, translating the results of such cell assays to vertebrates including human remains challenging. Therefore, we aim to evaluate whether zebrafish larvae (ZFL) could serve as a vertebrate screening model to detect gentamicin-induced changes of kidney glomeruli and proximal tubules. To validate the model, we compared the results of ZFL with those obtained from kidney biopsies of gentamicin-treated mice. We used transgenic zebrafish lines expressing enhanced green fluorescent proteins in the glomerulus to visualize glomerular damage. Synchrotron radiation-based computed tomography (SRμCT) is a label-free approach providing three-dimensional representations of renal structures with micrometre resolution. Clinically used gentamicin concentrations induce nephrotoxicity and affect glomerular and proximal tubular morphology. Findings were confirmed in mice and ZFL. There was a strong correlation between fluorescent signals in ZFL, SRμCT- derived descriptors of glomerular and proximal tubular morphology and the histological analysis of mouse kidney biopsies. A combination of SRμCT and confocal microscopy provides unprecedented insights into anatomical structures of the zebrafish kidney. Based on our findings, we suggest to use ZFL as a predictive vertebrate screening model to study drug-induced nephrotoxicity and to bridge the gap between cell culture-based test systems and experiments in mammals. Public Library of Science 2023-04-20 /pmc/articles/PMC10118166/ /pubmed/37079551 http://dx.doi.org/10.1371/journal.pone.0284562 Text en © 2023 Bolten et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Bolten, Jan Stephan Tanner, Christine Rodgers, Griffin Schulz, Georg Levano, Soledad Weitkamp, Timm Waldner, Samuel Puligilla, Ramya Deepthi Bodmer, Daniel Müller, Bert Huwyler, Jörg Zebrafish (Danio rerio) larvae as a predictive model to study gentamicin-induced structural alterations of the kidney |
title | Zebrafish (Danio rerio) larvae as a predictive model to study gentamicin-induced structural alterations of the kidney |
title_full | Zebrafish (Danio rerio) larvae as a predictive model to study gentamicin-induced structural alterations of the kidney |
title_fullStr | Zebrafish (Danio rerio) larvae as a predictive model to study gentamicin-induced structural alterations of the kidney |
title_full_unstemmed | Zebrafish (Danio rerio) larvae as a predictive model to study gentamicin-induced structural alterations of the kidney |
title_short | Zebrafish (Danio rerio) larvae as a predictive model to study gentamicin-induced structural alterations of the kidney |
title_sort | zebrafish (danio rerio) larvae as a predictive model to study gentamicin-induced structural alterations of the kidney |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10118166/ https://www.ncbi.nlm.nih.gov/pubmed/37079551 http://dx.doi.org/10.1371/journal.pone.0284562 |
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