Hearing disorders constitute one of the major health concerns in the USA. Decades of basic and clinical studies have identified numerous ototoxic agents and investigated their modes of action on the inner ear, utilizing tissue culture as well as animal and human models. Current preventive and therapeutic approaches are considered unsatisfactory. Therefore, additional modalities should be developed. Many studies suggest that increased levels of oxidative stress, chronic inflammation, and glutamate play an important role in the initiation and progression of damage to the inner ear leading to hearing impairments. To prevent these cellular deficits, antioxidants, anti-inflammatory agents, and antagonists of glutamate receptor have been used individually or in combination with limited success. It is essential, therefore, to simultaneously enhance the levels of antioxidant enzymes by activating the Nrf2 (a nuclear transcriptional factor) pathway, dietary and endogenous antioxidant compounds, and B12-vitamins in order to reduce the levels of oxidative stress, chronic inflammation, and glutamate at the same time. This review presents evidence to show that increased levels of these cellular metabolites, biochemical or factors are involved in the pathogenesis of cochlea leading to hearing impairments. It presents scientific rationale for the use of a mixture of micronutrients that may decrease the levels of oxidative damage, chronic inflammation, and glutamate at the same time. The benefits for using oral administration of proposed micronutrient mixture in humans are presented. Animal and limited human studies indirectly suggest that orally administered micronutrients can accumulate in the inner ear. Therefore, this route of administration may be useful in prevention, and in combination with standard care, in improved management of hearing problems following exposure to well-recognized and studied ototoxic agents, such as noise, cisplatin, aminoglycoside antibiotics, and advanced age.

中文翻译：

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氧化应激，炎症和谷氨酸盐增加：听力障碍的潜在预防和治疗目标。

听力障碍是美国主要的健康问题之一。数十年的基础和临床研究已经鉴定出许多耳毒性剂，并利用组织培养以及动物和人类模型研究了它们在内耳上的作用方式。当前的预防和治疗方法被认为是不令人满意的。因此，应开发其他方式。许多研究表明，氧化应激，慢性炎症和谷氨酸盐水平的升高在内耳损伤导致听力障碍的发生和发展中起着重要作用。为了防止这些细胞缺陷，抗氧化剂，抗炎剂和谷氨酸受体的拮抗剂已被单独使用或以有限的成功组合使用。因此，这是必不可少的 通过激活Nrf2（核转录因子）途径，饮食和内源性抗氧化剂化合物以及B12维生素来同时提高抗氧化酶的水平，从而同时降低氧化应激，慢性炎症和谷氨酸的水平。这项审查提供证据表明这些细胞代谢物，生化或因素的水平增加与耳蜗的发病机理有关，从而导致听力障碍。它为混合使用微量营养素提供了科学依据，这些微量营养素可同时降低氧化损伤，慢性炎症和谷氨酸的水平。提出了在人体内口服建议的微量营养素混合物的益处。动物研究和有限的人体研究间接表明，口服微量营养素可在内耳积聚。因此，这种给药途径可用于预防，并与标准护理相结合，可用于改善对暴露于公认的和研究的耳毒性剂（如噪音，顺铂，氨基糖苷类抗生素和高龄者）后的听力问题的管理。