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APAF-1 inhibition reduces cisplatin-induced hearing loss

AuthorsVarela-Nieto, Isabel CSIC ORCID ; Murillo-Cuesta, Silvia CSIC ORCID; Celaya, Adelaida M. CSIC ORCID; Rodriguez-de la Rosa, Lourdes CSIC ORCID; Cervantes, Blanca; García-Mato, Ángela; Sánchez-Pérez, Isabel; Herrero, Carmen CSIC ORCID
Issue Date2019
Citation42nd Congress of the Spanish Society of Biochemistry and Molecular Biology (2019)
AbstractCisplatin is an essential chemotherapeutic agent in the treatment of many cancers, especially in childhood cancers. Hearing loss is a common side-effect associated to cisplatin chemotherapy. Cisplatin induces apoptosis in inner ear hair cells by an APAF-1 dependentpathway. Here, we evaluated in vitro and in vivo the ability of an APAF-1 selective inhibitor, on the prevention of cisplatin-induced hearing loss. Our results showed that APAF-1 inhibitor i) bloked the formation of the apoptosome complex in vitro; ii) decreased cytochrome C release and caspase-3 activation, and increased HEIOC1 cells survival after cisplatin administration; and iii) induced a dose-dependent otoprotective effect after intratympanic administration, in rats receiving systemic cisplatin. All these data suggest that APAF-1 is an interesting molecular target and point APAF-1 inhibitors as promising putative potential therapeutic drug to prevent cisplatin-induced hearing loss.
DescriptionResumen del póster presentado al 42nd Congress of the Spanish Society of Biochemistry and Molecular Biology (SEBBM), celebrado en Madrid del 16 al 19 de julio de 2019.
Appears in Collections:(IIBM) Comunicaciones congresos

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