Cochlear Homocysteine Metabolism at the Crossroad of Nutrition and Sensorineural Hearing Loss.
Cochlear Homocysteine Metabolism at the Crossroad of Nutrition and Sensorineural Hearing Loss.
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DOI：
10.3389/fnmol.2017.00107
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发表时间：
2017
影响因子：
4.8
通讯作者：
Varela-Nieto I
中科院分区：
文献类型：
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作者：
Partearroyo T;Vallecillo N;Pajares MA;Varela-Moreiras G;Varela-Nieto I
根据世界卫生组织(WHO)的数据，听力损失(HL)是最常见的残疾原因之一，影响着3.6亿人。HL最常见的是感觉神经性起源，由毛细胞和/或螺旋神经节神经元的不可逆性丧失引起。感觉神经性HL(SNHL)的病因是多因素的，遗传和环境因素如噪声、耳毒性物质和衰老等起作用。营养状况是老年残疾的核心，但营养和SNHL之间的相互作用直到最近才得到关注。因此，在听力损伤达到不可逆转之前，饮食补充可能是预防和潜在修复听力损伤的第一步。在此背景下，不同的流行病学研究表明，营养状况、血浆总同型半胱氨酸(THcy)升高和SNHL之间存在相关性。几种人类遗传性罕见疾病也与同型半胱氨酸(Hcy)代谢和SNHL有关，证实了这种潜在的联系。因此，啮齿动物实验模型为理解观察到的效应提供了分子基础。因此，tHcy水平升高和维生素缺乏，如叶酸(FA)，与SNHL有关，而长期补充omega-3脂肪酸可改善Hcy代谢、细胞存活和听力。此外，针对同型半胱氨酸代谢的抗氧化剂富马酸的药理补充也改善了SNHL。总体而言，这些结果有力地表明，耳蜗同型半胱氨酸代谢在SNHL的发生和发展中起着关键作用，为设计前瞻性的营养疗法开辟了道路。
Hearing loss (HL) is one of the most common causes of disability, affecting 360 million people according to the World Health Organization (WHO). HL is most frequently of sensorineural origin, being caused by the irreversible loss of hair cells and/or spiral ganglion neurons. The etiology of sensorineural HL (SNHL) is multifactorial, with genetic and environmental factors such as noise, ototoxic substances and aging playing a role. The nutritional status is central in aging disability, but the interplay between nutrition and SNHL has only recently gained attention. Dietary supplementation could therefore constitute the first step for the prevention and potential repair of hearing damage before it reaches irreversibility. In this context, different epidemiological studies have shown correlations among the nutritional condition, increased total plasma homocysteine (tHcy) and SNHL. Several human genetic rare diseases are also associated with homocysteine (Hcy) metabolism and SNHL confirming this potential link. Accordingly, rodent experimental models have provided the molecular basis to understand the observed effects. Thus, increased tHcy levels and vitamin deficiencies, such as folic acid (FA), have been linked with SNHL, whereas long-term dietary supplementation with omega-3 fatty acids improved Hcy metabolism, cell survival and hearing acuity. Furthermore, pharmacological supplementations with the anti-oxidant fumaric acid that targets Hcy metabolism also improved SNHL. Overall these results strongly suggest that cochlear Hcy metabolism is a key player in the onset and progression of SNHL, opening the way for the design of prospective nutritional therapies.