Mechanisms and otoprotective strategies of programmed cell death on aminoglycoside-induced ototoxicity

Lei Han; Zijing Wang; Daqi Wang; Ziwen Gao; Shaowei Hu; Dazhi Shi; Yilai Shu

doi:10.3389/fcell.2023.1305433

Mechanisms and otoprotective strategies of programmed cell death on aminoglycoside-induced ototoxicity

Front Cell Dev Biol. 2024 Jan 8:11:1305433. doi: 10.3389/fcell.2023.1305433. eCollection 2023.

Authors

Lei Han^#^{1

2

3

4}, Zijing Wang^#^{1

2

3

4}, Daqi Wang^{2

3

4}, Ziwen Gao^{2

3

4}, Shaowei Hu^{2

3

4}, Dazhi Shi¹, Yilai Shu^{1

2

3

4}

Affiliations

¹ Department of Otorhinolaryngology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
² ENT Institute and Department of Otorhinolaryngology, Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.
³ Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
⁴ NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai, China.

^# Contributed equally.

Abstract

Aminoglycosides are commonly used for the treatment of life-threatening bacterial infections, however, aminoglycosides may cause irreversible hearing loss with a long-term clinical therapy. The mechanism and prevention of the ototoxicity of aminoglycosides are still limited although amounts of studies explored widely. Specifically, advancements in programmed cell death (PCD) provide more new perspectives. This review summarizes the general signal pathways in programmed cell death, including apoptosis, autophagy, and ferroptosis, as well as the mechanisms of aminoglycoside-induced ototoxicity. Additionally, novel interventions, especially gene therapy strategies, are also investigated for the prevention or treatment of aminoglycoside-induced hearing loss with prospective clinical applications.

Keywords: aminoglycosides; gene therapy; hair cell; ototoxicity; programmed cell death.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Key R&D Program of China (2020YFA0908201 and 2021YFA1101302), the National Natural Science Foundation of China (82225014, 82171148 and 82192864), the Shuguang Program of Shanghai Education Development Foundation and the Shanghai Municipal Education Commission (20SG08), Natural Science Foundation of Hunan Province (2021JJ70111), The Clinical Medical Technology Innovation Guidance Project of Department of Science and Technology of Hunan Provincial (2021SK51715).