Dose-dependent effect of chronic cisplatin administration upon cochlear hair cells

Introduction. Cisplatin administration results in outer hair cell (OHC) loss. Recent studies indicate a dose-dependency of cisplatin ototoxicity, but it is not easy to compare the results because of the variety of dosage schedules used. Therefore, we have systematically investigated the dose-dependency of cisplatin ototoxicity in the guinea-pig cochlea. Material and methods. Guinea-pigs were treated daily with intraperitoneal injections of cisplatin for 8 days in different dosages, i.e. 0.7 mg/kg/day (12 ears), 1.0 mg/kg/day (eight ears), 1.25 mg/kg/day (10 ears), 1.5 mg/kg/day (10 ears) and 20 mg/kg/day (18 ears), respectively. Hearing was measured electrophysiologically 1 day after treatment, followed by processing of the cochlea for histology. Results. The compound action potential (CAP) showed very small threshold shifts at doses of 0.7, 1.0 and 1.25 mg/kg/day. At a dose of 1.5 mg/kg/day, CAP showed a significant increase in threshold. No significant OHC loss was seen at doses of 0.7, 1.0 and 1.25 mg/kg/day. At a dose of 1.5 mg/kg/day, significant loss of OHC in the basal and middle turns was present. The electrophysiological and histological results are in agreement. Conclusion. Cisplatin ototoxicity is dose-related. The largest transition in cisplatin ototoxicity occurs at a dose between 1.25 and 1.5 mg/kg/day in an 8-day dosing schedule.