International immunopharmacology · 2026
Dimethyl fumarate alleviates oxidative stress and inflammation in noise-induced hearing loss by activating Nrf2/HO-1 signaling in cochlear hair cells.
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Li Moyang, Zhang Weijian, Huang Xiaotong, Fu Minyi, Zhang Jiahui, Chen Junrong, Pang Jiaqi, Yang Haidi
Аннотация
OBJECTIVES: Noise-induced hearing loss (NIHL) is an acquired sensorineural hearing impairment resulting from acoustic overexposure, primarily mediated by oxidative stress, inflammation and synaptic excitotoxicity. However, no FDA-approved drugs exist currently for NIHL. Dimethyl fumarate (DMF), an FDA-approved Nrf2 activator, is known for its antioxidant, anti-inflammatory and neuroprotective properties. This study aimed to investigate the therapeutic potential of DMF in mitigating NIHL by alleviating oxidative stress and inflammation.
METHODS: Oxidative damage and apoptosis models were established in HEI-OC1 cells using hydrogen peroxide (H2O2). Raw 264.7 cells were treated with lipopolysaccharide (LPS) to induce an inflammation model. DCFH-DA staining and flow cytometry were used to assess oxidative damage and apoptosis degree. To establish the model of noise-induced hearing loss, CBA/J mice were exposed to broadband noise (1 to 20 kHz, 108 dB SPL) for 2 h. Auditory brainstem response(ABR) test was used to measure the hearing function after DMF treatment. Immunofluorescence, western blot and qRT-PCR were used to analyze the protein localization and the signaling pathways.
RESULTS: DMF treatment significantly increased nuclear Nrf2 expression and ameliorated hydrogen peroxide-induced oxidative stress, cell apoptosis and inflammation, while cotreatment with ML385, an Nrf2 inhibitor, abolished the protective effects. Additionally, systemic application of DMF significantly preserved auditory function, reduced damage to outer hair cells and ribbon synapses in noise-exposed mice by activating the Nrf2/HO-1 signaling pathway.
CONCLUSION: Our findings indicate that DMF is a promising therapeutic candidate for preventing NIHL.
METHODS: Oxidative damage and apoptosis models were established in HEI-OC1 cells using hydrogen peroxide (H2O2). Raw 264.7 cells were treated with lipopolysaccharide (LPS) to induce an inflammation model. DCFH-DA staining and flow cytometry were used to assess oxidative damage and apoptosis degree. To establish the model of noise-induced hearing loss, CBA/J mice were exposed to broadband noise (1 to 20 kHz, 108 dB SPL) for 2 h. Auditory brainstem response(ABR) test was used to measure the hearing function after DMF treatment. Immunofluorescence, western blot and qRT-PCR were used to analyze the protein localization and the signaling pathways.
RESULTS: DMF treatment significantly increased nuclear Nrf2 expression and ameliorated hydrogen peroxide-induced oxidative stress, cell apoptosis and inflammation, while cotreatment with ML385, an Nrf2 inhibitor, abolished the protective effects. Additionally, systemic application of DMF significantly preserved auditory function, reduced damage to outer hair cells and ribbon synapses in noise-exposed mice by activating the Nrf2/HO-1 signaling pathway.
CONCLUSION: Our findings indicate that DMF is a promising therapeutic candidate for preventing NIHL.