Neuroprotection of vestibular sensory cells from gentamicin ototoxicity obtained using nitric oxide synthase inhibitors, reactive oxygen species scavengers, brain-derived neurotrophic factors and calpain inhibitors
Neuroprotection of vestibular sensory cells from gentamicin ototoxicity obtained using nitric oxide synthase inhibitors, reactive oxygen species scavengers, brain-derived neurotrophic factors and calpain inhibitors
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DOI：
10.1080/0036554021000028078
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发表时间：
2003-01-01
影响因子：
1.4
通讯作者：
Watanabe, H
中科院分区：
文献类型：
--
作者：
Takumida, M;Anniko, M;Watanabe, H
为了设计一种新的治疗内耳疾病的方法，（L-N-G-硝基精氨酸甲酯[L-NAME]），自由基清除剂（D-甲硫氨酸），神经营养蛋白（脑源性神经营养因子[BDNF]）和钙蛋白酶抑制剂材料和方法-这些药物对庆大霉素的影响-用荧光指示剂4，5-二氨基荧光素二乙酸酯和二氢四甲基玫瑰胺研究了一氧化氮（NO）和活性氧（ROS）的诱导产生。结果L-NAME抑制NO的产生，D-蛋氨酸和BDNF抑制ROS的产生，亮肽素对NO和ROS均无抑制作用。所有药物均能减轻庆大霉素对前庭毛细胞的损伤。组合L-NAME + BDNF，L-NAME +亮抑酶肽和D-蛋氨酸+ BDNF有一个显着更强的预防作用，对毛细胞damage.Conclusion-It建议，联合治疗与自由基抑制剂和神经营养因子或钙蛋白酶抑制剂可能有助于更有效地治疗内耳疾病。
Objective-In order to devise a new treatment for inner ear disorders, the efficacy of a nitric oxide synthase inhibitor (L-N-G-nitroarginine methylester [L-NAME]), a radical scavenger (D-methionine), a neurotrophin (brain-derived neurotrophic factor [BDNF]) and a calpain inhibitor (leupeptin) for protection from hair cell damage was investigated.Material and methods-The effects of these drugs on gentamicin-induced production of nitric oxide (NO) and reactive oxygen species (ROS) were studied by means of the fluorescence indicators 4,5-diaminofluorescein diacetate and dihydrotetramethylrosamine. The effect on gentamicin-induced vestibular hair cell damage was examined by using an in vitro LIVE/DEAD system.Results-L-NAME inhibited the production of NO, D-methionine and BDNF restricted the production of ROS and leupeptin inhibited neither NO nor ROS. All the drugs used limited the vestibular hair cell damage caused by gentamicin. The combinations L-NAME + BDNF, L-NAME + leupeptin and D-methionine + BDNF had a significantly stronger preventive effect on hair cell damage.Conclusion-It is suggested that combined treatment with a radical inhibitor and either a neurotrophin or calpain inhibitor may help to treat inner ear disorders more effectively.