Using the Zebrafish Lateral Line to Uncover Novel Mechanisms of Action and Prevention in Drug-Induced Hair Cell Death

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.