End points for cisplatin ototoxicity.

INTRODUCTION

Hearing loss owing to ototoxicity in humans is usually presumed to be irreversible and stable. Most articles in the literature study the effects of ototoxic agents such as cisplatin only over a few days or weeks. This study focused on the recovery of hearing over several months in mice. The same treatment was applied to guinea pigs to determine whether there were significant differences in response between the two species.

METHODS

Thirty-two mice and 37 guinea pigs were randomized to receive either saline or cisplatin (15 mg/kg). After this exposure, we performed auditory brainstem response (ABR) testing on the mice over 8 months and on the guinea pigs for 1 month.

RESULTS

Hearing loss owing to cisplatin shows significant variability between and within species. In mice, hearing loss is maximal at about 17 dB during the third month after cisplatin administration but actually improves to the level attributable to presbyacusis. Guinea pigs, however, experience greater, approximately 25 dB hearing loss within a month of administration of the same dose of cisplatin, tested with the same protocol.

CONCLUSION

In general, ototoxicity end points should be assessed more than 1 month after exposure for animals. Our observation that hearing loss is incomplete before 1 month in mice opens the possibility of studies for preventive treatment during that time.