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 ototoxicity were investigated. Hamsters were given a series of 5 cisplatin injections (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 protection was given by STS, followed by DDTC. WR-2721 and fosfomycin did not provide any protection. All of the animals in the STS and DDTC groups survived, while some fatalities occurred in the fosfomycin, WR-2721, and cisplatin-only groups. Thus, the agents that were protective against ototoxicity were also protective against mortality. The ABRs also provided evidence of cisplatin-induced neuropathy. In summary, STS and DDTC hold promise for ameliorating the ototoxic effects of cisplatin chemotherapy and the hamster proved to be an excellent model of cisplatin ototoxicity.
Church
M W
MW
Department of Obstetrics and Gynecology, Wayne State University, School of Medicine, Detroit, MI, USA.
Kaltenbach
J A
JA
Blakley
B W
BW
Burgio
D L
DL
D004999:Amifostine / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000931:Antidotes / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D001309:Auditory Threshold / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D006224:Cricetinae; D004050:Ditiocarb / Q000494:pharmacology; D004347:Drug Interactions; D004594:Electrophysiology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005578:Fosfomycin / Q000494:pharmacology; D006198:Hair Cells, Auditory / Q000166:cytology / Q000187:drug effects; D006319:Hearing Loss, Sensorineural / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D008297:Male; D008647:Mesocricetus; D008855:Microscopy, Electron, Scanning; D011837:Radiation-Protective Agents / Q000494:pharmacology; D011897:Random Allocation; D013885:Thiosulfates / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000931:Antidotes; D000970:Antineoplastic Agents; D011837:Radiation-Protective Agents; D013885:Thiosulfates; D005578:Fosfomycin; D004050:Ditiocarb; C017717:sodium thiosulfate; D004999:Amifostine; D002945:Cisplatin