Protection of both auditory hair cells and auditory neurons from cisplatin induced damage
Protection of both auditory hair cells and auditory neurons from cisplatin induced damage
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DOI：
10.3109/00016489709117778
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发表时间：
1997-03-01
影响因子：
1.4
通讯作者：
VandeWater, TR
中科院分区：
文献类型：
--
作者：
Gabaizadeh, R;Staecker, H;VandeWater, TR
顺铂是一种有效的抗肿瘤药物，用于治疗头颈部鳞状细胞癌，但有严重的副作用。一个严重的副作用是损害听觉毛细胞和听觉神经元。对神经元的损害已被证明是直接的影响，而不是由于毛细胞提供的神经营养支持的丧失。几种神经营养素已被证明可以减轻顺铂诱导的体外听觉神经元损伤的程度，但这些神经营养素对毛细胞的损伤程度没有影响。已证明D-甲硫氨酸（D-met）可在体内和体外对顺铂的肾毒性和耳毒性提供保护。在这项研究中，脑源性神经营养因子（BDNF）与D-met的组合表明，听觉神经元和听毛细胞都可以保护顺铂诱导的体外损伤。这些结果表明，这种类型的联合治疗（即神经营养因子与自由基清除剂的组合）可以为听觉受体提供比这些药物单独使用更完全的保护，以对抗顺铂毒性。由于BDNF和D-met在体外均显示出营养活性，因此我们提出这些药物的组合也将提供有效的保护以对抗体内顺铂诱导的听觉受体的耳毒性和神经毒性。
Cisplatin is an effective anti-neoplastic agent used in the treatment of squamous cell cancer of the head and neck, but with serious side effects. One serious side effect is damage to both the auditory hair cells and the auditory neurons. The damage to the neurons has been shown to be a direct effect and not due to the loss of the neurotrophic support provided by the hair cells. Several neurotrophins have been shown to lessen the extent of cisplatin induced damage of auditory neurons in vitro, but these neurotrophins have had no effect on the extent of damage to the hair cells. D-methionine (D-met) has been demonstrated to provide protection against cisplatin's nephrotoxicity in vivo and ototoxicity in vitro. In this study the combination of brain derived neurotrophic factor (BDNF) with D-met has shown that both auditory neurons and auditory hair cells can be protected from cisplatin induced damage in vitro. These results demonstrate that this type of combination therapy (i.e. a neurotrophin combined with a free radical scavenger) can provide more complete protection for the auditory receptor against cisplatin toxicity than either of these agents alone. Because both BDNF and D-met have been shown to have trophic activity in vitro we proposed that the combination of these agents will also provide effective protection against cisplatin induced ototoxicity and neurotoxicity of the auditory receptor in vivo.