Engage Global, 245 El Faisan Drive, San Rafael, CA, 94903, United States.
Center for Occupational and Environmental Health, Department of Medicine, University of California, Irvine, CA, 92697-1830, United States.
Mech Ageing Dev. 2020 Jan;185:111191. doi: 10.1016/j.mad.2019.111191. Epub 2019 Nov 22.
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.
听力障碍是美国主要的健康问题之一。几十年来的基础和临床研究已经确定了许多耳毒性药物，并利用组织培养以及动物和人体模型研究了它们对内耳的作用方式。目前的预防和治疗方法被认为是不令人满意的。因此，应该开发其他方法。许多研究表明，氧化应激、慢性炎症和谷氨酸水平的增加在内耳损伤的发生和进展中起着重要作用，导致听力受损。为了预防这些细胞缺陷，已经单独或联合使用抗氧化剂、抗炎剂和谷氨酸受体拮抗剂，但取得的效果有限。因此，通过激活 Nrf2（核转录因子）途径、饮食和内源性抗氧化化合物以及 B12 维生素来同时提高抗氧化酶的水平，以降低氧化应激、慢性炎症和谷氨酸的水平是至关重要的。这篇综述提供了证据表明，这些细胞代谢物、生化或因素水平的增加参与了耳蜗的发病机制，导致听力受损。它为使用可能同时降低氧化损伤、慢性炎症和谷氨酸水平的混合微量营养素提供了科学依据。还介绍了在人类中口服给予所提议的微量营养素混合物的益处。动物和有限的人体研究间接表明，口服给予的微量营养素可以在内耳中积累。因此，这种给药途径可能有助于预防，并与标准护理结合，改善暴露于公认和研究充分的耳毒性药物（如噪声、顺铂、氨基糖苷类抗生素和高龄）后的听力问题的管理。
