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The protective effect of aspirin-induced temporary threshold shift in an animal model of cisplatin-related ototoxicity

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Abstract

Purpose

The purpose of this study was to evaluate whether induction of temporary threshold shift (TTS) with aspirin prior to cisplatin exposure can prevent or minimize cisplatin detrimental effects on hearing.

Methods

We randomly divided BALB mice into three groups: (1) cisplatin only, (2) aspirin only, and (3) combined aspirin/cisplatin. Cisplatin was administered as a single intraperitoneal injection of 14 mg/kg. Aspirin was administered for three weeks via intraperitoneal injection of 200 mg/kg sodium salicylate, twice daily. Air conduction thresholds were recorded using Auditory Brainstem Responses (ABR). Cochleae were harvested and cochlear hair cells were counted using a scanning electron microscope (SEM).

Results

Aspirin-induced TTS have reached an average of 30.05±16.9 dB after 2 weeks. At 60 days, cisplatin-only treated mice experienced an average threshold shifts of 50.7 dB at 4 kHz, 35.16 dB at 8 kHz, 70 dB at 16 kHz, 53.1 dB at 32 kHz. All threshold shifts were significantly worse than for cisplatin/aspirin treated mice with TTS of 11.85 dB at 4 kHz, 3.58 dB at 8 kHz, 16.58  dB at 16 kHz, 20.41 dB at 32 kHz (p < 0.01). Cochlear cell count with SEM has shown reduction in the number of both inner and outer hair cells in the mid-turn in cisplatin treated mice.

Conclusion

Aspirin induced TTS can protect from cisplatin-induced ototoxicity. This beneficial effect was demonstrated by auditory thresholds as well as SEM. Larger pre-clinical and clinical studies are still needed to confirm these findings.

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Data and materials availability

The data generated in this study are available upon request from the corresponding author.

Abbreviations

ABR:

Auditory brainstem responses

TTS:

Temporary threshold shift

SEM:

Scanning electron microscope

IHC:

Inner hair cells

OHC:

Outer hair cells

DPOAEs:

Distortion product otoacoustic emissions

SGCs:

Spiral ganglion cells

BID:

Twice a day

TID:

Three times a day

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Acknowledgements

We thank Advanced Bionics for their technical support and guidance and Dr. Ofir Zavdy for illustration assistance.

Funding

This study was supported by a research grant provided by Rabin Medical Center, Israel.

Author information

Authors and Affiliations

  1. Department of Otorhinolaryngology Head and Neck Surgery, Rabin Medical Center, 39 Jabotinsky St, Petah Tikva, Israel

    Sharon Tzelnick, Aviram Mizrachi, Shaked Shivatzki, Eyal Yosefof, Elad Hikri & Ohad Hilly

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Sharon Tzelnick, Aviram Mizrachi, Shaked Shivatzki, Eyal Yosefof, Elad Hikri & Ohad Hilly

  3. Institute of Audiology and Clinical Neurophysiology, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

    Neta Barkan & Joseph Attias

  4. Department of Communications Sciences and Disorders, Haifa University, Haifa, Israel

    Joseph Attias

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  1. Sharon Tzelnick
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  2. Aviram Mizrachi
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  3. Neta Barkan
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Contributions

ST performed the majority of the experimental work and wrote the manuscript, AM conceptualized the research, reviewed, and edited the manuscript, NB performed the experimental work, SS performed the histological analysis, EY performed the experimental work, YA conceptualized the research, reviewed, and edited the manuscript and OH conceptualized the research, reviewed, and edited the manuscript.

Corresponding author

Correspondence to Sharon Tzelnick.

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Conflict of interest

The authors declare that they have no competing interests.

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All housing and experimental procedures were reviewed and approved by Rabin Medical Center Institutional Animal Care and Use Committee (020502).

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Tzelnick, S., Mizrachi, A., Barkan, N. et al. The protective effect of aspirin-induced temporary threshold shift in an animal model of cisplatin-related ototoxicity. J Cancer Res Clin Oncol 149, 2009–2016 (2023). https://doi.org/10.1007/s00432-022-04144-5

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  • DOI: https://doi.org/10.1007/s00432-022-04144-5

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