Age-related hearing loss patterns in Fischer 344/NHsd rats with cisplatin-induced hearing loss

The current study was undertaken to explore the impact of cisplatin ototoxicity at a young adult age on the development of age-related hearing loss, both in terms of age of onset and severity of the hearing loss. For the study, 21 Fischer 344/NHsd rats were tested. All rats were tested for auditory brainstem responses (ABRs) at age 7 months and then 15 of the rats were exposed to 7 mg/kg cisplatin by intra-peritoneal infusion. The other 6 rats received saline infusions to serve as controls. Seven of the cisplatin rats were euthanized after an ABR test 7 days after cisplatin exposure to assess acute damage. The other 14 rats were tested monthly until age 18 months. Cisplatin caused acute ABR threshold shift at 30 and 40 kHz, but that acute hearing loss led to less age-related hearing loss at those frequencies. Cisplatin exposure led to a primarily additive interaction with age-related hearing loss at 20 kHz, with some exacerbation of hearing loss at age 16-18 months, along with a larger lesion of missing outer hair cells in the corresponding region of the cochlea. ABR P1 amplitude input-output functions were not significantly affected by the cisplatin exposure when controlling for threshold shift. Results indicate that cisplatin ototoxicity and age-related hearing loss interact antagonistically in the cochlear region damaged by cisplatin, and primarily show an additive interaction in the frequencies lower than the focus of the cisplatin damage.