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Updated: Aug 2, 2025
Kidney Regeneration in Adult Zebrafish by Gentamicin Induced Injury
Published on: August 3, 2015
Zebrafish (Danio rerio) larvae as a predictive model to study gentamicin-induced structural alterations of the kidney
Jan Stephan Bolten1, Christine Tanner2, Griffin Rodgers2
1Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
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.
Insights
Zebrafish larvae (ZFL) effectively model drug-induced kidney damage, correlating with mouse studies. This vertebrate model aids in predicting nephrotoxicity, bridging the gap between cell assays and mammalian experiments.
Area of Science:
- Pharmacology
- Toxicology
- Developmental Biology
Background:
- Drug-induced nephrotoxicity is a critical safety concern in drug development.
- In vitro cell-based assays for renal toxicity have limitations in predicting in vivo effects.
- A reliable vertebrate model is needed to bridge the gap between cell assays and mammalian studies.
Purpose of the Study:
- To evaluate zebrafish larvae (ZFL) as a vertebrate screening model for gentamicin-induced nephrotoxicity.
- To assess ZFL's ability to detect changes in kidney glomeruli and proximal tubules.
- To validate ZFL findings against mouse kidney biopsy data.
Main Methods:
- Utilized transgenic zebrafish expressing fluorescent proteins in glomeruli to visualize damage.
- Employed synchrotron radiation-based micro-computed tomography (SRμCT) for label-free, high-resolution 3D imaging of renal structures.
- Compared ZFL results with histological analysis of kidney biopsies from gentamicin-treated mice.
Main Results:
- Clinically relevant gentamicin concentrations induced observable nephrotoxicity in ZFL, affecting glomerular and proximal tubular morphology.
- Findings in ZFL were consistent with those observed in gentamicin-treated mice.
- A strong correlation was found between ZFL fluorescent signals, SRμCT-derived morphological descriptors, and mouse kidney histology.
Conclusions:
- Zebrafish larvae serve as a predictive vertebrate screening model for drug-induced nephrotoxicity.
- The combination of SRμCT and confocal microscopy offers detailed insights into zebrafish kidney anatomy.
- ZFL models can help bridge the gap between in vitro cell systems and mammalian experiments for drug safety assessment.
