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Melatonin Alleviates the Oxygen–Glucose Deprivation/Reperfusion-Induced Pyroptosis of HEI-OC1 Cells and Cochlear Hair Cells via MT-1,2/Nrf2 (NFE2L2)/ROS/NLRP3 Pathway

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Abstract

Substantial evidence suggests that pyroptosis is involved in renal, cerebral, and myocardial ischemia–reperfusion injury. However, whether pyroptosis is involved in ischemia–reperfusion injury of cochlear hair cells has not been explored. In this study, we examined the effects of melatonin on the oxygen–glucose deprivation/reperfusion (OGD/R) of hair cell-like House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and cochlear hair cells in vitro to mimic cochlear ischemia–reperfusion injury in vivo. We found that melatonin treatment protected the HEI-OC1 and cochlear hair cells against OGD/R-induced cell pyroptosis and reduced the expression level of ROS in these cells. However, these effects were completely abolished by the application of luzindole (a non-selective melatonin receptor blocker) and largely offset by the use of ML385 (an nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor). These findings suggest that melatonin alleviates OGD/R-induced pyroptosis of the hair cell-like HEI-OC1 cells and cochlear hair cells via the melatonin receptor 1A (MT-1) and melatonin receptor 1B (MT-2)/Nrf2 (NFE2L2)/ROS/NLRP3 pathway, which may provide credible evidence for melatonin being used as a potential drug for the treatment of idiopathic sudden sensorineural hearing loss in the future.

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Data Availability

The datasets during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 81970889 to FL.C) and the Science and Technology Committee of Shanghai (grant number 22S31903100 to FL.C).

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Author notes

  1. Yu Zheng, Na Gao and Weixun Zhang contributed equally to this work..

Authors and Affiliations

  1. Department of Otorhinolaryngology, Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, 200031, China

    Yu Zheng, Na Gao, Weixun Zhang, Rui Ma, Fanglu Chi, Zhen Gao & Ning Cong

  2. Shanghai Clinical Medical Center of Hearing Medicine, Shanghai, 200031, China

    Yu Zheng, Na Gao, Weixun Zhang, Rui Ma, Fanglu Chi, Zhen Gao & Ning Cong

  3. NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai, 20031, People’s Republic of China

    Yu Zheng, Na Gao, Weixun Zhang, Rui Ma, Fanglu Chi, Zhen Gao & Ning Cong

  4. Research Institute of Otorhinolaryngology, Fudan University, Shanghai, 200031, China

    Yu Zheng, Na Gao, Weixun Zhang, Rui Ma, Fanglu Chi, Zhen Gao & Ning Cong

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  1. Yu Zheng
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Contributions

FLC, ZG, and NC contributed to conception and design of the study. YZ, NG, WXZ, and RM performed the experiments. YZ, NG, and WXZ wrote the manuscript. FLC, ZG, and NC reviewed and edited the manuscript. All authors read and approved the manuscript.

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Correspondence to Fanglu Chi, Zhen Gao or Ning Cong.

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All animal experiments were performed in line with the principles of the Institutional Animal Care and Use Committee of the Eye & ENT Hospital of Fudan University.

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Zheng, Y., Gao, N., Zhang, W. et al. Melatonin Alleviates the Oxygen–Glucose Deprivation/Reperfusion-Induced Pyroptosis of HEI-OC1 Cells and Cochlear Hair Cells via MT-1,2/Nrf2 (NFE2L2)/ROS/NLRP3 Pathway. Mol Neurobiol 60, 629–642 (2023). https://doi.org/10.1007/s12035-022-03077-x

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