Church M W, Kaltenbach J A, Blakley B W, Burgio D L
Department of Obstetrics and Gynecology, Wayne State University, School of Medicine, Detroit, MI, USA.
Hear Res. 1995 Jun;86(1-2):195-203. doi: 10.1016/0378-5955(95)00066-d.
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.
研究了四种药物改善顺铂诱导的耳毒性的效果。仓鼠接受一系列5次顺铂注射（3毫克/千克/次，每隔一天腹腔注射一次），单独注射或与1600毫克/千克/次硫代硫酸钠（STS）、300毫克/千克/次二乙氨基二硫代甲酸盐（DDTC）、18毫克/千克/次WR-2721或300毫克/千克/次磷霉素联合注射（每组n = 10）。通过听性脑干反应（ABR）进行电生理评估耳毒性，通过耳蜗组织学进行解剖学评估。STS提供了最大的听觉保护，其次是DDTC。WR-2721和磷霉素没有提供任何保护。STS组和DDTC组的所有动物均存活，而磷霉素组、WR-2721组和仅顺铂组出现了一些死亡。因此，对耳毒性有保护作用的药物对死亡率也有保护作用。ABR也提供了顺铂诱导的神经病变的证据。总之，STS和DDTC有望改善顺铂化疗的耳毒性作用，仓鼠被证明是顺铂耳毒性的优秀模型。
