Cisplatin-induced threshold shift in the CBA/CaJ, C57BL/6J, BALB/cJ mouse models of hearing loss

The development of a clinically-relevant rodent model of cisplatin-induced hearing loss presents the challenges of finding the cumulative dose, dosing schedule, and rodent strain to induce a consistent level of threshold shift with low mortality. This study was undertaken to model hearing loss at 16, 32, and 48 mg/kg cumulative doses of cisplatin in the CBA/CaJ, C57BL/6J, and BALB/cJ mouse strains. Mice were exposed to three cycles of 16 mg/kg cisplatin, for a cumulative dose of 48 mg/kg. Equal numbers of male and female mice were used in each strain, and the cisplatin was delivered in three different dosing schedules: a single bolus dose of 16 mg/kg followed by 20 days of recovery, 8 mg/kg doses delivered every ten days, and 4 mg/kg delivered daily for four consecutive days followed by 17 days of recovery. Auditory brainstem response threshold shifts indicated increased hearing loss with increasing cumulative dose in all strains and dosing schedules. The BALB/cJ experienced the largest threshold shifts, and the C57BL/6J the smallest. However, the BALB/cJ mice had the lowest mortality (0%) of the strains. The dosing schedule had minimal effects on threshold shift, but did affect mortality, with the 16 mg/kg single dose inducing more mortality than the other two schedules. In the BALB/cJ mice, the males experienced more threshold shift than the females. The results mirror past work comparing the three strains' susceptibility to kanamycin ototoxicity, with highest pigmentation showing the lowest acute susceptibility to cisplatin-induced hearing loss, and the albino strain showing the highest susceptibility.