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Rutin Attenuates Gentamycin-induced Hair Cell Injury in the Zebrafish Lateral Line via Suppressing STAT1

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Abstract

Aminoglycoside antibiotics, including gentamicin (GM), induce delayed ototoxic effects such as hearing loss after prolonged use, which results from the death of hair cells. However, the mechanisms underlying the ototoxicity of aminoglycosides warrant further investigation, and there are currently no effective drugs in the clinical setting. Herein, the therapeutic effect of the flavonoid compound rutin against the ototoxic effects of GM in zebrafish hair cells was investigated. Animals incubated with rutin (100–400 µmol/L) were protected against the pernicious effects of GM (200 µmol/L). We found that rutin improves hearing behavior in zebrafish, and rutin was effective in reducing the number of Tunel-positive cells in the neuromasts of the zebrafish lateral line and promoting cell proliferation after exposure to GM. Subsequently, rutin exerted a protective effect against GM-induced cell death in HEI-OC1 cells and could limit the production of cytosolic reactive oxygen species (ROS) and diminish the percentage of apoptotic cells. Additionally, the results of the proteomic analysis revealed that rutin could effectively inhibit the expression of necroptosis and apoptosis related genes. Meanwhile, molecular docking analysis revealed a high linking activity between the molecular docking of rutin and STAT1 proteins. The protection of zebrafish hair cells or HEI-OC1 cells from GM-induced ototoxicity by rutin was attenuated by the introduction of STAT1 activator. Finally, we demonstrated that rutin significantly improves the bacteriostatic effect of GM by in vitro experiments, emphasising its clinical application value. In summary, these results collectively unravel a novel therapeutic role for rutin as an otoprotective drug against the adverse effects of GM.

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Acknowledgements

This research was funded by the Qingdao Medical and Health Research guidance Project (2022-WJZD107) and the National Natural Science Foundation of China (Nos. 82000979).

Funding

This research was funded by the Qingdao Medical and Health Research guidance Project (2022-WJZD107) and the National Natural Science Foundation of China (Nos. 82000979).

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Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, 250012, Shandong, China

    Huiming Yang

  2. Affiliated Qingdao Third People’s Hospital, Department of Otorhinolaryngology Head and Neck, Qingdao University, Qingdao, 266021, China

    Tao Zong, Jing Liu, Tong Xu & Rong Yang

  3. Department of Physiology and Pathophysiology, Medical school of Qingdao University, Qingdao, China

    Dengxu Wang

  4. The First Faculty of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China

    Ke Gong

  5. Jining Key Laboratory of Pharmacology, School of Basic Medical Science, Jining Medical University, No. 133, Hehua Road, Jining, 272067, Shandong, China

    Haiyan Yin

  6. Department of Otolaryngology, Tengzhou Central People’s Hospital, Tengzhou, Shandong, China

    Weiwei Zhang

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  1. Huiming Yang
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  2. Tao Zong
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  3. Jing Liu
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Contributions

HY and RY designed the experiments; HY performed the animal experiments; TZ, JL, and DW performed the experiments; KG, HY and WZ analyzed the data, reviewed the data, advised the study, and interpreted the analyzed data; HY and TX wrote the manuscript. The manuscript has been revised and approved by all authors.

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Correspondence to Tong Xu or Rong Yang.

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This study was approved by the Animal Ethics Committee (No.20,230,506) of Shandong Provincial Hospital (Jinan, China).

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Yang, H., Zong, T., Liu, J. et al. Rutin Attenuates Gentamycin-induced Hair Cell Injury in the Zebrafish Lateral Line via Suppressing STAT1. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04179-4

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