Caspase inhibitor z-VAD-FMK increases the survival of hair cells after Actinomycin-D-induced damage in vitro.

Huimin Chang, Fei Sun, Keyong Tian, Weilong Wang, Ke Zhou, Dingjun Zha, Jianhua Qiu

Neuroscience letters 2020 Jul 27

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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. Co-treatment 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. Copyright © 2020. Published by Elsevier B.V.

Citation

Huimin Chang, Fei Sun, Keyong Tian, Weilong Wang, Ke Zhou, Dingjun Zha, Jianhua Qiu. Caspase inhibitor z-VAD-FMK increases the survival of hair cells after Actinomycin-D-induced damage in vitro. Neuroscience letters. 2020 Jul 27;732:135089