Takumida M, Anniko M, Popa R, Zhang D M
Department of Otolaryngology, Hiroshima University School of Medicine, Japan.
Acta Otolaryngol. 2001 Jan;121(1):16-20. doi: 10.1080/000164801300006218.
Nitric oxide (NO)-mediated neurotoxicity may be an appropriate pathophysiological model with which to explain a variety of inner ear diseases characterized by acute or progressive hearing loss, tinnitus and vertigo. The localization of NO synthase (NOS) isoforms was examined in the inner ear of the pigmented guinea pig after intratympanic injection of 1 mg lipopolysaccharide (LPS) or 5 mg gentamicin (GM) using an immunohistochemical method, revealing the expression of NOS II in the inner ear. Production of NO in the isolated organ of Corti and utricle or in the isolated vestibular and cochlear hair cells after stimulation with L-arginine, glutamate, GM and LPS was investigated using the fluorescence indicator 4,5-diaminofluorescein diacetate. The fluorescence intensity of the sensory cells was augmented by stimulation with L-arginine, glutamate, GM and LPS. A significant increase in NO production was also noted in the LPS-treated animals. These findings imply that NO from constitutive NOS may mediate ototoxicity in the early phase, whereas NO from NOS II may contribute to the late phase of tissue damage in the inner ear. Based on this hypothesis, reduction of glutamatergic excitotoxicity and inhibition of NOS, scavenging superoxide and scavenging peroxynitrite are thought to attenuate NO-mediated otoneurotoxicity.
一氧化氮（NO）介导的神经毒性可能是一种合适的病理生理模型，可用于解释各种以内耳疾病，这些疾病的特征为急性或进行性听力丧失、耳鸣和眩晕。采用免疫组化方法，在鼓室内注射1毫克脂多糖（LPS）或5毫克庆大霉素（GM）后，检测了有色豚鼠内耳中一氧化氮合酶（NOS）同工型的定位，结果显示内耳中有NOS II的表达。使用荧光指示剂4,5-二氨基荧光素二乙酸酯，研究了用L-精氨酸、谷氨酸、GM和LPS刺激后，分离的柯蒂氏器和椭圆囊或分离的前庭及耳蜗毛细胞中NO的产生情况。L-精氨酸、谷氨酸、GM和LPS刺激可增强感觉细胞的荧光强度。在LPS处理的动物中，也观察到NO产生显著增加。这些发现表明，组成型NOS产生的NO可能在早期介导耳毒性，而NOS II产生的NO可能在内耳组织损伤的后期起作用。基于这一假设，减少谷氨酸能兴奋性毒性、抑制NOS、清除超氧化物和清除过氧亚硝酸盐被认为可减轻NO介导的耳神经毒性。
