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The study used zebrafish to investigate drug-induced hair cell death and identify protective agents. Zebrafish were ideal due to their genetic similarities to mammals and external hair cells. Researchers found three zebrafish mutants resistant to neomycin-induced hair cell death, involving genes not previously linked to hair cell toxicity. They screened 10,960 compounds, identifying several protective agents, including FDA-approved drugs. The study revealed that many protective compounds did not affect the bactericidal activity of aminoglycosides, except Benzamil. Selective estrogen receptor modulators were effective against neomycin exposure. The research highlighted disrupted calcium homeostasis as a mechanism of hair cell toxicity, with calcium release from the endoplasmic reticulum causing mitochondrial dysfunction and increased reactive oxygen species. The zebrafish model was effective in understanding hair cell death mechanisms and identifying potential treatments for hearing loss and balance disorders.

The study used the zebrafish lateral line system to screen for compounds that induce or protect against hair cell loss, identifying 21 compounds that caused hair cell death and two compounds, PROTO1 and PROTO2, that protected against neomycin-induced damage. These findings demonstrated the zebrafish model's potential for identifying ototoxic drugs and protective agents, suggesting clinical applications for hearing protection. The research emphasized the need for standardized drug screening to prevent hearing loss and further exploration of drug delivery methods and protective pathways.