THE COMPARATIVE EFFECTS OF SODIUM THIOSULFATE, DIETHYLDITHIOCARBAMATE, FOSFOMYCIN AND WR-2721 ON AMELIORATING CISPLATIN-INDUCED OTOTOXICITY

The efficacies of four agents in ameliorating cisplatin-induced ototox icity were investigated. Hamsters were given a series of 5 cisplatin i njections (3 mg/kg/injection once every other day, i.p.) either alone or in combination with 1600 mg/kg/injection sodium thiosulfate (STS), 300 mg/kg/injection diethyldithiocarbamate (DDTC), 18 mg/kg/injection WR-2721, or 300 mg/kg/injection fosfomycin (n = 10/group). Ototoxicity was assessed electrophysiologically by auditory brainstem responses ( ABRs) and anatomically by cochlear histology. The greatest auditory pr otection was given by STS, followed by DDTC. WR-2721 and fosfomycin di d not provide any protection. All of the animals in the STS and DDTC g roups survived, while some fatalities occurred in the fosfomycin, WR-2 721, and cisplatin-only groups. Thus, the agents that were protective against ototoxicity were also protective against mortality. The ABRs a lso provided evidence of cisplatin-induced neuropathy. In summary, STS and DDTC hold promise for ameliorating the ototoxic effects of cispla tin chemotherapy and the hamster proved to be an excellent model of ci splatin ototoxicity.