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Updated: Dec 13, 2025
Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish
Published on: May 15, 2021
The identification of dual protective agents against cisplatin-induced oto- and nephrotoxicity using the zebrafish
Jaime N Wertman1,2, Nicole Melong2,3, Matthew R Stoyek4
1Dalhousie University, Department of Microbiology and Immunology, Halifax, Canada.
Abstract:
Dose-limiting toxicities for cisplatin administration, including ototoxicity and nephrotoxicity, impact the clinical utility of this effective chemotherapy agent and lead to lifelong complications, particularly in pediatric cancer survivors. Using a two-pronged drug screen employing the zebrafish lateral line as an in vivo readout for ototoxicity and kidney cell-based nephrotoxicity assay, we screened 1280 compounds and identified 22 that were both oto- and nephroprotective. Of these, dopamine and L-mimosine, a plant-based amino acid active in the dopamine pathway, were further investigated. Dopamine and L-mimosine protected the hair cells in the zebrafish otic vesicle from cisplatin-induced damage and preserved zebrafish larval glomerular filtration. Importantly, these compounds did not abrogate the cytotoxic effects of cisplatin on human cancer cells. This study provides insights into the mechanisms underlying cisplatin-induced oto- and nephrotoxicity and compelling preclinical evidence for the potential utility of dopamine and L-mimosine in the safer administration of cisplatin.
Insights
Dopamine and L-mimosine protect against cisplatin
Area of Science:
- Oncology
- Toxicology
- Pharmacology
Background:
- Cisplatin is an effective chemotherapy agent but causes dose-limiting toxicities like ototoxicity and nephrotoxicity.
- These toxicities lead to lifelong complications, especially in pediatric cancer survivors.
Purpose of the Study:
- To identify compounds that protect against cisplatin-induced oto- and nephrotoxicity.
- To evaluate the potential of dopamine and L-mimosine as protective agents during cisplatin treatment.
Main Methods:
- A two-pronged drug screen using zebrafish lateral line for ototoxicity and kidney cell assays for nephrotoxicity.
- Screened 1280 compounds to identify oto- and nephroprotective agents.
- Investigated dopamine and L-mimosine for their protective mechanisms and efficacy.
Main Results:
- Identified 22 compounds with both oto- and nephroprotective properties.
- Dopamine and L-mimosine demonstrated protection of hair cells and preserved kidney function in zebrafish models.
- These protective agents did not interfere with cisplatin's cytotoxic effects on cancer cells.
Conclusions:
- Dopamine and L-mimosine show potential for mitigating cisplatin-induced toxicities.
- Provides preclinical evidence for safer cisplatin administration, particularly benefiting pediatric cancer survivors.
- Offers insights into the mechanisms of cisplatin-induced oto- and nephrotoxicity.
