The role of intratympanic lactate injection in the prevention of cisplatin-induced ototoxicity

Authors

  • Marc-Elie Nader MD,

    1. Department of Otolaryngology–Head and Neck Surgery, Sainte-Justine University Hospital Center (CHU SJ), Montreal University, Montreal, Quebec, Canada
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  • Yves Théorêt BPharm, PhD,

    1. Department of Otolaryngology–Head and Neck Surgery, Sainte-Justine University Hospital Center (CHU SJ), Montreal University, Montreal, Quebec, Canada
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  • Issam Saliba MD

    Corresponding author
    1. Department of Otolaryngology–Head and Neck Surgery, Sainte-Justine University Hospital Center (CHU SJ), Montreal University, Montreal, Quebec, Canada
    • CHU Sainte-Justine, 3175, Côte Sainte-Catherine, Service ORL, Montreal (Qc) H3T 1C5, Canada
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  • The authors have no funding, financial relationships, or conflicts of interest to disclose.

Abstract

Objectives/Hypothesis:

There is no approved agent to prevent cisplatin-induced ototoxicity. Our objectives were to: 1) identify and compare the effect of intratympanic injections of lactate or N-acetylcysteine (NAC) in the prevention of cisplatin-induced ototoxicity, 2) investigate inner ear protection using a scanning electron microscope, and 3) study systemic diffusion of intratympanic NAC.

Study Design:

Prospective animal study.

Methods:

Sixteen guinea pigs formed two groups, and respectively received intratympanic lactate and 20% NAC in one ear. The contralateral ears received a control saline solution. After 30 minutes, an intraperitoneal cisplatin injection of 3 mg/kg was performed and repeated eight times, once a week, to achieve 24 mg/kg. Auditory brainstem responses (ABRs) were recorded before any injection, after 9 mg/kg and after 24 mg/kg of cisplatin for the frequencies 2, 4, 6 and 8 kHz. Cochleas were analyzed under scanning electron microscope. Systemic diffusion of NAC was studied using high-performance liquid chromatography.

Results:

For the control ears, ABR thresholds increased uniformly and averaged 28.4 dB. The lactate group showed a lower threshold increase and averaged 17.0 dB. The NAC showed an important threshold increase of 89.0 dB. Lactate showed a significant hearing protection at 2000 Hz (P < .01). Electron microscopy revealed partial preservation of outer hair cell stereocilia for the ears treated with lactate and severe disruption for NAC group. No systemic diffusion of NAC was observed with chromatography.

Conclusions:

Intratympanic lactate offers significant partial protection against cisplatin-induced ototoxicity at midfrequencies. High-concentration NAC does not seem a viable solution as it causes a considerable inflammatory reaction. NAC does not diffuse systemically.

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