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A combinatorial approach to protect sensory tissue against cisplatin-induced ototoxicity.

Authors:
Nicole K Febles Mark A Bauer Bo Ding Xiaoxia Zhu Nathan D Gallant Robert D Frisina

Hear Res 2022 03 10;415:108430. Epub 2022 Jan 10.

Department of Medical Engineering, University of South Florida, Tampa, FL 33620, USA; Department of Communicative Sciences and Disorders, University of South Florida, Tampa, FL 33602, USA; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33602, USA. Electronic address:

Sensorineural Hearing Loss (SNHL) is a highly prevalent disorder involving permanent damage or loss to the inner ear's mechano-sensory hair cells and nerve fibers. Major contributing causes are ototoxic drugs, loud noises, and aging. Drug-induced hearing loss (DIHL), affects over 25% of patients treated with common therapeutics such as aminoglycoside antibiotics, loop diuretics or chemotherapeutics. A commonly used chemotherapeutic agent, cisplatin, is very effective for treating malignant tumors, but results in a majority of patients experiencing irreversible hearing loss and/or tinnitus. Additionally, since there is currently no FDA-approved treatments for SNHL, attenuation of ototoxicity is a major area of investigation in oncology, otolaryngology and hearing research. Several potential otoprotective agents have been investigated at the clinical trial stage, but none have progressed to a full FDA-approval. In this study, we investigated a combinatorial approach comprised of an antioxidant, a p53 inhibitor and a neurotrophin, as a multifactorial otoprotective treatment for cisplatin exposure. In vitro, HEI-OC1 cells, an immortalized organ of Corti epithelial cell line, pre-treated with this biotherapeutic cocktail had significantly reduced cisplatin-induced cell death, DNA fragmentation, and apoptotic activation. In an ex vivo study, rat pup D2-D3 organ of Corti explants, significant protection against cisplatin-based hair cell and neuronal loss was achieved by delivery of the same combinatorial pretreatment. Interestingly, the hair cell protection was localized to the basal and middle regions of the organ of Corti. Together, these findings highlight a novel approach to attenuate cisplatin ototoxicity and potentially prevent DIHL by addressing biological mechanisms of cisplatin ototoxicity.

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http://dx.doi.org/10.1016/j.heares.2022.108430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810742PMC
March 2022

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