Dietary intake of deuterium oxide decreases cochlear metabolism and oxidative stress levels in a mouse model of age-related hearing loss.

Dietary intake of deuterium oxide decreases cochlear metabolism and oxidative stress levels in a mouse model of age-related hearing loss.
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DOI:
10.1016/j.redox.2022.102472
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发表时间:
2022-11
期刊:
影响因子:
11.4
通讯作者:
Yang, Jun
Yang, Jun
中科院分区:
生物学1区
文献类型:
--
作者:
Hou, Shule;Chen, Penghui;He, Jingchun;Chen, Junmin;Zhang, Jifang;Mammano, Fabio;Yang, Jun

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老年性听力损失(ARHL)是老年人最常见的感觉障碍。目前,没有任何治疗方法可以有效预防或逆转ARHL。听觉器官的老化往往伴随着氧化应激和代谢恶化的加剧。在这里,我们报告的影响,氘代氧(D2 O),也被称为“重水”,小鼠模型的ARHL。与未处理的对照组相比,在4至9周龄的正常小鼠饮食中补充10%D2O降低了治疗小鼠在选定频率下的听力阈值。氧化应激水平显着降低,并在处理与未处理的小鼠的耳蜗管。通过代谢通量分析发现,D2 O主要减缓分解代谢反应,可能在一定程度上延缓与衰老相关的代谢恶化。实验证实,Nrf 2/HO-1/谷胱甘肽轴在处理的小鼠中下调。因此,D2 O补充剂可以通过减慢代谢速度和减少耳蜗中内源性氧化应激产生来阻碍小鼠模型中的ARHL进展。这些发现为保护耳蜗免受氧化应激和调节代谢以预防ARHL开辟了新途径。
Age-related hearing loss (ARHL) is the most prevalent sensory disorder in the elderly. Currently, no treatment can effectively prevent or reverse ARHL. Aging auditory organs are often accompanied by exacerbated oxidative stress and metabolic deterioration. Here, we report the effect of deuterated oxygen (D2O), also known as “heavy water”, mouse models of ARHL. Supplementing the normal mouse diet with 10% D2O from 4 to 9 weeks of age lowered hearing thresholds at selected frequencies in treated mice compared to untreated control group. Oxidative stress levels were significantly reduced and in the cochlear duct of treated vs. untreated mice. Through metabolic flux analysis, we found that D2O mainly slowed down catabolic reactions, and may delay metabolic deterioration related to aging to a certain extent. Experiments confirmed that the Nrf2/HO-1/glutathione axis was down-regulated in treated mice. Thus, D2O supplementation can hinder ARHL progression in mouse models by slowing the pace of metabolism and reducing endogenous oxidative stress production in the cochlea. These findings open new avenues for protecting the cochlea from oxidative stress and regulating metabolism to prevent ARHL.
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