Journal
NEUROSCIENCE LETTERS
Volume 732, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2020.135089
Keywords
Actinomycin-D; Hair cells; Spiral ganglion neurons; Apoptosis; Reactive oxygen species
Categories
Funding
- National Natural Science Foundation of Major Projects Overseas of China [81120108008]
- National Natural Science Foundation of China [81700904, 81670925]
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Actinomycin-D (Act-D) is a highly effective chemotherapeutic agent that induces apoptosis in systemic tissues. Act-D combined with other chemotherapeutic agents exhibits ototoxic effects and causes hearing impairment. To investigate the potential toxic effects of Act-D in the inner ear, we treated cochlear organotypic cultures with varying concentrations of Act-D for different durations. For the first time, we found that Act-D specifically induced HC loss and apoptosis in a dose- and time-dependent manner but not neuronal degeneration. Cotreatment with benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-FMK), a pan cysteine protease inhibitor, significantly reduced HC loss and apoptosis induced by Act-D, indicating increased cell survival. Taken together, Act-D exposure has ototoxic effects on the auditory system, while z-VAD-FMK prevents Act-D-induced hair cell damage.
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