Dietary intake of deuterium oxide decreases cochlear metabolism and oxidative stress levels in a mouse model of age-related hearing loss
Shule Hou,
Penghui Chen,
Jingchun He,
Junmin Chen,
Jifang Zhang,
Fabio Mammano,
Jun Yang
Affiliations
Shule Hou
Department of Otorhinolaryngology-Head & Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Jiaotong University School of Medicine Ear Institute, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Penghui Chen
Department of Otorhinolaryngology-Head & Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Jiaotong University School of Medicine Ear Institute, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China; Corresponding author. Department of Otorhinolaryngology-Head & Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Jingchun He
Department of Otorhinolaryngology-Head & Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Jiaotong University School of Medicine Ear Institute, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Junmin Chen
Department of Otorhinolaryngology-Head & Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Jiaotong University School of Medicine Ear Institute, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Jifang Zhang
Department of Otorhinolaryngology-Head & Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Jiaotong University School of Medicine Ear Institute, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Fabio Mammano
Department of Physics and Astronomy “G. Galilei”, University of Padua, Padova, Italy; Department of Biomedical Sciences, Institute of Cell Biology and Neurobiology, Italian National Research Council, Monterotondo, Italy; Corresponding author. Department of Physics and Astronomy “G. Galilei”, University of Padua, Padova, Italy.
Jun Yang
Department of Otorhinolaryngology-Head & Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Jiaotong University School of Medicine Ear Institute, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China; Corresponding author. Department of Otorhinolaryngology-Head & Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
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.
