The identification of 1 dual protective agents against cisplatin-induced oto- and nephrotoxicity using the zebrafish model

Jaime N. Wertman, Nicole Melong, Matthew R. Stoyek, Olivia Piccolo, Stewart Langley, Benno Orr, Shelby L. Steele, Babak Razaghi, Jason N. Berman

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

20 Citas (Scopus)

Resumen

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-24 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 oto27 and nephrotoxicity and compelling preclinical evidence for the potential utility of dopamine and L-mimosine in the safer administration of cisplatin.

Idioma originalEnglish
Número de artículoe56235
Páginas (desde-hasta)1-59
Número de páginas59
PublicacióneLife
Volumen9
DOI
EstadoPublished - jul. 2020

Nota bibliográfica

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ASJC Scopus Subject Areas

  • General Neuroscience
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology

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