COMPARISON OF 5 AGENTS IN PROTECTING THE COCHLEA AGAINST THE OTOTOXICEFFECTS OF CISPLATIN IN THE HAMSTER

The purpose of this investigation was to study the ameliorating effect s of four agents on cisplatin-induced ototoxicity. Hamsters were given a series of five cisplatin injections either alone or in combination with sodium thiosulfate (STS), diethyldihydrothiocarbamate (DDTC), and S-2(3-aminopropylamino) ethylphosphorothioic acid (WR-2721), or fosfo mycin. Ototoxicity was assessed anatomically by quantifying the extent of cochlear damage with the scanning electron microscope and physiolo gically with measures of the auditory brain stem response. When admini stered alone, cisplatin induced widespread loss of outer hair cells (O HCs) along much of the cochlea in the hamster, especially in the basal and middle turns, with an average survival of only 56% of the OHC pop ulation. In contrast, inner hair cells resisted cisplatin ototoxicity in the hamster. Thus the ameliorative effects of the different test ag ents were assessed by counting the number of surviving OHCs in each tr eatment group and comparing with cisplatin-treated controls. STS provi ded the most effective protection against the ototoxic effects of cisp latin, yielding 91% survival of OHCs. DDTC also reduced the ototoxic e ffects of cisplatin, yielding 68% survival of OHCs. Cotreatment with W R-2721 and fosfomycin yielded 45% and 52% OHC survival, respectively a nd thus did not provide any chemoprotection. The results closely paral leled those based on auditory brain stem response recordings in that t he magnitude of threshold shift was proportional to the amount of OHC loss; also, the amount of threshold shift at each frequency was in goo d agreement with the pattern of hair cell loss along the cochlear spir al. Thus both histologic and physiologic results suggest that STS and DDTC hold promise for ameliorating the ototoxic effects of cisplatin c hemotherapy.