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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:PloS one 2023-04, Vol.18 (4), p.e0284562-e0284562
Hauptverfasser: Bolten, Jan Stephan, Tanner, Christine, Rodgers, Griffin, Schulz, Georg, Levano, Soledad, Weitkamp, Timm, Waldner, Samuel, Puligilla, Ramya Deepthi, Bodmer, Daniel, Müller, Bert, Huwyler, Jörg
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page e0284562
container_issue 4
container_start_page e0284562
container_title PloS one
container_volume 18
creator Bolten, Jan Stephan
Tanner, Christine
Rodgers, Griffin
Schulz, Georg
Levano, Soledad
Weitkamp, Timm
Waldner, Samuel
Puligilla, Ramya Deepthi
Bodmer, Daniel
Müller, Bert
Huwyler, Jörg
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.
doi_str_mv 10.1371/journal.pone.0284562
format Article
fullrecord <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2803893740</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A746371079</galeid><doaj_id>oai_doaj_org_article_6cc8dcc3a4e5481eabe12d512786467f</doaj_id><sourcerecordid>A746371079</sourcerecordid><originalsourceid>FETCH-LOGICAL-c594t-de1ce485fc20df4a5243988100b4ac85ff9ae2c72ee17ebcf6b9efe303ff9b6b3</originalsourceid><addsrcrecordid>eNptUk1v1DAQjRCIlsI_QGCJSzlksWPHcU6oKl-VKnGBCxdrYo93vWTjxU5W2n-Pl02rLqp8sDXz5s3M8yuK14wuGG_Yh3WY4gD9YhsGXNBKiVpWT4pz1vKqlBXlTx-8z4oXKa0prbmS8nlxxhvatHXNzovpF3YRnE8rcvkJBh9IxOjDe9JD3AESSATINqL1ZvQ7JJtgsSdjIGmc7J4scRhh440fSj_YyaDNiTiZcYrQE-hHjDD6MCQSHBlXSH57O-D-ZfHMQZ_w1XxfFD-_fP5x_a28_f715vrqtjR1K8bSIjMoVO1MRa0TUFeCt0oxSjsBJsddC1iZpkJkDXbGya5Fh5zynOlkxy-Kt0febR-SnhVLulKUq5Y3gmbEzRFhA6z1NvoNxL0O4PW_QIhLDXH0pkctjVHWGA4Ca6EYQoessjWrGiWFbFzm-jh3m7oNWpO1ySqckJ5mBr_Sy7DTjDKmmJSZ4XJmiOHPhGnUG58M9j0MGKbj4K3kSh2g7_6DPr7ejFpC3sAPLuTG5kCqrxohs4-yETJq8QgqH4v5b7O_nM_xkwJxLDAxpBTR3S_JqD64824YfXCnnt2Zy948FOi-6M6O_C8lMORV</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2803893740</pqid></control><display><type>article</type><title>Zebrafish (Danio rerio) larvae as a predictive model to study gentamicin-induced structural alterations of the kidney</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Public Library of Science (PLoS)</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Bolten, Jan Stephan ; Tanner, Christine ; Rodgers, Griffin ; Schulz, Georg ; Levano, Soledad ; Weitkamp, Timm ; Waldner, Samuel ; Puligilla, Ramya Deepthi ; Bodmer, Daniel ; Müller, Bert ; Huwyler, Jörg</creator><contributor>Máthé, Domokos</contributor><creatorcontrib>Bolten, Jan Stephan ; Tanner, Christine ; Rodgers, Griffin ; Schulz, Georg ; Levano, Soledad ; Weitkamp, Timm ; Waldner, Samuel ; Puligilla, Ramya Deepthi ; Bodmer, Daniel ; Müller, Bert ; Huwyler, Jörg ; Máthé, Domokos</creatorcontrib><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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0284562</identifier><identifier>PMID: 37079551</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Animal experimentation ; Animals ; Antibiotics ; Auroral kilometric radiation ; Biology and Life Sciences ; Biopsy ; Cell culture ; Computed tomography ; Confocal microscopy ; Danio rerio ; Drug discovery ; Engineering and Technology ; Ethanol ; Evaluation ; Experiments ; Fluorescence ; Gentamicin ; Gentamicins - toxicity ; Glomerulus ; Histology ; Humans ; Kidney - diagnostic imaging ; Kidney - pathology ; Kidney Diseases - pathology ; Kidney Glomerulus - pathology ; Kidneys ; Larva ; Larvae ; Lasers ; Mammals ; Medicine and Health Sciences ; Mice ; Microscopy ; Modelling ; Morphology ; Pharmacovigilance ; Prediction models ; Proximal tubules ; Radiation ; Radiation damage ; Research and Analysis Methods ; Screening ; Synchrotron radiation ; Synchrotrons ; Toxicity ; Transgenic mice ; Vertebrates ; Zebra fish ; Zebrafish</subject><ispartof>PloS one, 2023-04, Vol.18 (4), p.e0284562-e0284562</ispartof><rights>Copyright: © 2023 Bolten et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2023 Public Library of Science</rights><rights>2023 Bolten et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 Bolten et al 2023 Bolten et al</rights><rights>2023 Bolten et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c594t-de1ce485fc20df4a5243988100b4ac85ff9ae2c72ee17ebcf6b9efe303ff9b6b3</citedby><cites>FETCH-LOGICAL-c594t-de1ce485fc20df4a5243988100b4ac85ff9ae2c72ee17ebcf6b9efe303ff9b6b3</cites><orcidid>0000-0002-0374-0472 ; 0000-0003-1748-5676</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10118166/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10118166/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37079551$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Máthé, Domokos</contributor><creatorcontrib>Bolten, Jan Stephan</creatorcontrib><creatorcontrib>Tanner, Christine</creatorcontrib><creatorcontrib>Rodgers, Griffin</creatorcontrib><creatorcontrib>Schulz, Georg</creatorcontrib><creatorcontrib>Levano, Soledad</creatorcontrib><creatorcontrib>Weitkamp, Timm</creatorcontrib><creatorcontrib>Waldner, Samuel</creatorcontrib><creatorcontrib>Puligilla, Ramya Deepthi</creatorcontrib><creatorcontrib>Bodmer, Daniel</creatorcontrib><creatorcontrib>Müller, Bert</creatorcontrib><creatorcontrib>Huwyler, Jörg</creatorcontrib><title>Zebrafish (Danio rerio) larvae as a predictive model to study gentamicin-induced structural alterations of the kidney</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Analysis</subject><subject>Animal experimentation</subject><subject>Animals</subject><subject>Antibiotics</subject><subject>Auroral kilometric radiation</subject><subject>Biology and Life Sciences</subject><subject>Biopsy</subject><subject>Cell culture</subject><subject>Computed tomography</subject><subject>Confocal microscopy</subject><subject>Danio rerio</subject><subject>Drug discovery</subject><subject>Engineering and Technology</subject><subject>Ethanol</subject><subject>Evaluation</subject><subject>Experiments</subject><subject>Fluorescence</subject><subject>Gentamicin</subject><subject>Gentamicins - toxicity</subject><subject>Glomerulus</subject><subject>Histology</subject><subject>Humans</subject><subject>Kidney - diagnostic imaging</subject><subject>Kidney - pathology</subject><subject>Kidney Diseases - pathology</subject><subject>Kidney Glomerulus - pathology</subject><subject>Kidneys</subject><subject>Larva</subject><subject>Larvae</subject><subject>Lasers</subject><subject>Mammals</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Microscopy</subject><subject>Modelling</subject><subject>Morphology</subject><subject>Pharmacovigilance</subject><subject>Prediction models</subject><subject>Proximal tubules</subject><subject>Radiation</subject><subject>Radiation damage</subject><subject>Research and Analysis Methods</subject><subject>Screening</subject><subject>Synchrotron radiation</subject><subject>Synchrotrons</subject><subject>Toxicity</subject><subject>Transgenic mice</subject><subject>Vertebrates</subject><subject>Zebra fish</subject><subject>Zebrafish</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUk1v1DAQjRCIlsI_QGCJSzlksWPHcU6oKl-VKnGBCxdrYo93vWTjxU5W2n-Pl02rLqp8sDXz5s3M8yuK14wuGG_Yh3WY4gD9YhsGXNBKiVpWT4pz1vKqlBXlTx-8z4oXKa0prbmS8nlxxhvatHXNzovpF3YRnE8rcvkJBh9IxOjDe9JD3AESSATINqL1ZvQ7JJtgsSdjIGmc7J4scRhh440fSj_YyaDNiTiZcYrQE-hHjDD6MCQSHBlXSH57O-D-ZfHMQZ_w1XxfFD-_fP5x_a28_f715vrqtjR1K8bSIjMoVO1MRa0TUFeCt0oxSjsBJsddC1iZpkJkDXbGya5Fh5zynOlkxy-Kt0febR-SnhVLulKUq5Y3gmbEzRFhA6z1NvoNxL0O4PW_QIhLDXH0pkctjVHWGA4Ca6EYQoessjWrGiWFbFzm-jh3m7oNWpO1ySqckJ5mBr_Sy7DTjDKmmJSZ4XJmiOHPhGnUG58M9j0MGKbj4K3kSh2g7_6DPr7ejFpC3sAPLuTG5kCqrxohs4-yETJq8QgqH4v5b7O_nM_xkwJxLDAxpBTR3S_JqD64824YfXCnnt2Zy948FOi-6M6O_C8lMORV</recordid><startdate>20230420</startdate><enddate>20230420</enddate><creator>Bolten, Jan Stephan</creator><creator>Tanner, Christine</creator><creator>Rodgers, Griffin</creator><creator>Schulz, Georg</creator><creator>Levano, Soledad</creator><creator>Weitkamp, Timm</creator><creator>Waldner, Samuel</creator><creator>Puligilla, Ramya Deepthi</creator><creator>Bodmer, Daniel</creator><creator>Müller, Bert</creator><creator>Huwyler, Jörg</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-0374-0472</orcidid><orcidid>https://orcid.org/0000-0003-1748-5676</orcidid></search><sort><creationdate>20230420</creationdate><title>Zebrafish (Danio rerio) larvae as a predictive model to study gentamicin-induced structural alterations of the kidney</title><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></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c594t-de1ce485fc20df4a5243988100b4ac85ff9ae2c72ee17ebcf6b9efe303ff9b6b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Analysis</topic><topic>Animal experimentation</topic><topic>Animals</topic><topic>Antibiotics</topic><topic>Auroral kilometric radiation</topic><topic>Biology and Life Sciences</topic><topic>Biopsy</topic><topic>Cell culture</topic><topic>Computed tomography</topic><topic>Confocal microscopy</topic><topic>Danio rerio</topic><topic>Drug discovery</topic><topic>Engineering and Technology</topic><topic>Ethanol</topic><topic>Evaluation</topic><topic>Experiments</topic><topic>Fluorescence</topic><topic>Gentamicin</topic><topic>Gentamicins - toxicity</topic><topic>Glomerulus</topic><topic>Histology</topic><topic>Humans</topic><topic>Kidney - diagnostic imaging</topic><topic>Kidney - pathology</topic><topic>Kidney Diseases - pathology</topic><topic>Kidney Glomerulus - pathology</topic><topic>Kidneys</topic><topic>Larva</topic><topic>Larvae</topic><topic>Lasers</topic><topic>Mammals</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Microscopy</topic><topic>Modelling</topic><topic>Morphology</topic><topic>Pharmacovigilance</topic><topic>Prediction models</topic><topic>Proximal tubules</topic><topic>Radiation</topic><topic>Radiation damage</topic><topic>Research and Analysis Methods</topic><topic>Screening</topic><topic>Synchrotron radiation</topic><topic>Synchrotrons</topic><topic>Toxicity</topic><topic>Transgenic mice</topic><topic>Vertebrates</topic><topic>Zebra fish</topic><topic>Zebrafish</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bolten, Jan Stephan</creatorcontrib><creatorcontrib>Tanner, Christine</creatorcontrib><creatorcontrib>Rodgers, Griffin</creatorcontrib><creatorcontrib>Schulz, Georg</creatorcontrib><creatorcontrib>Levano, Soledad</creatorcontrib><creatorcontrib>Weitkamp, Timm</creatorcontrib><creatorcontrib>Waldner, Samuel</creatorcontrib><creatorcontrib>Puligilla, Ramya Deepthi</creatorcontrib><creatorcontrib>Bodmer, Daniel</creatorcontrib><creatorcontrib>Müller, Bert</creatorcontrib><creatorcontrib>Huwyler, Jörg</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bolten, Jan Stephan</au><au>Tanner, Christine</au><au>Rodgers, Griffin</au><au>Schulz, Georg</au><au>Levano, Soledad</au><au>Weitkamp, Timm</au><au>Waldner, Samuel</au><au>Puligilla, Ramya Deepthi</au><au>Bodmer, Daniel</au><au>Müller, Bert</au><au>Huwyler, Jörg</au><au>Máthé, Domokos</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Zebrafish (Danio rerio) larvae as a predictive model to study gentamicin-induced structural alterations of the kidney</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2023-04-20</date><risdate>2023</risdate><volume>18</volume><issue>4</issue><spage>e0284562</spage><epage>e0284562</epage><pages>e0284562-e0284562</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>37079551</pmid><doi>10.1371/journal.pone.0284562</doi><orcidid>https://orcid.org/0000-0002-0374-0472</orcidid><orcidid>https://orcid.org/0000-0003-1748-5676</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1932-6203
ispartof PloS one, 2023-04, Vol.18 (4), p.e0284562-e0284562
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_2803893740
source MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry
subjects Analysis
Animal experimentation
Animals
Antibiotics
Auroral kilometric radiation
Biology and Life Sciences
Biopsy
Cell culture
Computed tomography
Confocal microscopy
Danio rerio
Drug discovery
Engineering and Technology
Ethanol
Evaluation
Experiments
Fluorescence
Gentamicin
Gentamicins - toxicity
Glomerulus
Histology
Humans
Kidney - diagnostic imaging
Kidney - pathology
Kidney Diseases - pathology
Kidney Glomerulus - pathology
Kidneys
Larva
Larvae
Lasers
Mammals
Medicine and Health Sciences
Mice
Microscopy
Modelling
Morphology
Pharmacovigilance
Prediction models
Proximal tubules
Radiation
Radiation damage
Research and Analysis Methods
Screening
Synchrotron radiation
Synchrotrons
Toxicity
Transgenic mice
Vertebrates
Zebra fish
Zebrafish
title Zebrafish (Danio rerio) larvae as a predictive model to study gentamicin-induced structural alterations of the kidney
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T09%3A24%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Zebrafish%20(Danio%20rerio)%20larvae%20as%20a%20predictive%20model%20to%20study%20gentamicin-induced%20structural%20alterations%20of%20the%20kidney&rft.jtitle=PloS%20one&rft.au=Bolten,%20Jan%20Stephan&rft.date=2023-04-20&rft.volume=18&rft.issue=4&rft.spage=e0284562&rft.epage=e0284562&rft.pages=e0284562-e0284562&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0284562&rft_dat=%3Cgale_plos_%3EA746371079%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2803893740&rft_id=info:pmid/37079551&rft_galeid=A746371079&rft_doaj_id=oai_doaj_org_article_6cc8dcc3a4e5481eabe12d512786467f&rfr_iscdi=true