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Changes in otoacoustic emissions and auditory brain stem response after cis-platinum exposure in gerbils
1Division of Otolaryngology-Head and Neck Surgery, Children's Hospital and Medical Center, Seattle, WA 98105, USA.
Abstract:
Ototoxicity associated with cis-platinum administration commonly presents as hearing loss and tinnitus. The hearing loss is usually an irreversible, high-frequency sensorineural loss. Histologic studies in humans and animals suggest that the outer hair cells (OHCs) are most susceptible to cis-platinum. Evoked otoacoustic emissions (EOAE), as a measure of outer hair cell function, are potentially useful in following ototoxic insults involving OHCs. Distortion-product otoacoustic emissions (DPOAE) test frequency-specific regions of the cochlea and therefore may be particularly well suited for monitoring ototoxic injuries. We measured distortion product otoacoustic emissions, at f2 = 2, 4, 6, 8, 10, and 12 kHz, in gerbils after a single large dose of cis-platinum. Animals treated with saline served as controls. The findings were compared to auditory brain stem evoked response (ABR) thresholds, using tone pips of the same frequencies. The DPOAE and ABR thresholds were measured before treatment and again 2, 5, and 14 days after drug administration. The changes in DPOAE were compared with the changes in ABR. No treatment effect was noted in the 2-day group. Animals treated with cis-platinum demonstrated significant elevation of DPOAE and ABR thresholds compared with control animals at 5 and 14 days. There was no significant difference between the threshold changes in the 5- and 14-day groups.
Insights
Cis-platinum causes hearing loss by damaging outer hair cells (OHCs). Distortion-product otoacoustic emissions (DPOAE) effectively monitor this ototoxicity, showing significant threshold changes in gerbils post-treatment.
Area of Science:
- Ototoxicology
- Auditory Neuroscience
- Pharmacology
Background:
- Cis-platinum chemotherapy is known to cause ototoxicity, manifesting as irreversible hearing loss and tinnitus.
- Histological evidence indicates that outer hair cells (OHCs) are particularly vulnerable to cis-platinum.
- Evoked otoacoustic emissions (EOAE) offer a non-invasive method to assess OHC function and monitor ototoxic effects.
Purpose of the Study:
- To evaluate the utility of distortion-product otoacoustic emissions (DPOAE) in monitoring cis-platinum-induced ototoxicity.
- To compare DPOAE threshold changes with auditory brain stem evoked response (ABR) thresholds following cis-platinum administration in gerbils.
Main Methods:
- Distortion-product otoacoustic emissions (DPOAE) and auditory brain stem evoked response (ABR) thresholds were measured in gerbils at multiple frequencies (2-12 kHz) before and at 2, 5, and 14 days after a single large dose of cis-platinum.
- Control animals received saline injections.
- Changes in DPOAE thresholds were compared with corresponding changes in ABR thresholds.
Main Results:
- No significant ototoxic effects were observed at the 2-day post-treatment mark.
- Cis-platinum treated gerbils showed significant elevations in both DPOAE and ABR thresholds at 5 and 14 days compared to controls.
- No significant difference was found in the magnitude of threshold changes between the 5-day and 14-day measurement points.
Conclusions:
- Distortion-product otoacoustic emissions (DPOAE) are sensitive to cis-platinum-induced ototoxicity in gerbils.
- DPOAE measurements, alongside ABR, can effectively track hearing damage caused by cis-platinum, particularly affecting outer hair cell function.
- These findings support the use of DPOAE as a valuable tool for monitoring cis-platinum ototoxicity in preclinical settings.