2,3,4',5‑Tetrahydroxystilbene‑2‑O‑β‑D‑glucoside ameliorates gentamicin‑induced ototoxicity by modulating autophagy via Sesn2/AMPK/mTOR signaling

Wen,Yu-Hsuan; Lin,Hui-Yi; Lin,Jia-Ni; Tseng,Guo-Fang; Hwang,Chung-Feng; Lin,Chung-Ching; Hsu,Chuan-Jen; Wu,Hung-Pin

doi:10.3892/ijmm.2022.5127

2,3,4',5‑Tetrahydroxystilbene‑2‑O‑β‑D‑glucoside ameliorates gentamicin‑induced ototoxicity by modulating autophagy via Sesn2/AMPK/mTOR signaling

Authors:
- Yu-Hsuan Wen
- Hui-Yi Lin
- Jia-Ni Lin
- Guo-Fang Tseng
- Chung-Feng Hwang
- Chung-Ching Lin
- Chuan-Jen Hsu
- Hung-Pin Wu
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Affiliations: Institute of Medical Sciences, Tzu Chi University, Hualien 970374, Taiwan, R.O.C., School of Pharmacy, College of Pharmacy, China Medical University, Taichung 404328, Taiwan, R.O.C., Department of Otolaryngology, Head and Neck Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427213, Taiwan, R.O.C., Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan, R.O.C.
Published online on: March 29, 2022 https://doi.org/10.3892/ijmm.2022.5127
Article Number: 71
Copyright: © Wen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gentamicin is an important aminoglycoside antibiotic used in the treatment of gram‑negative bacterial infections, but nephrotoxicity and ototoxicity reduce its utility. The autophagy pathway is involved in damage of auditory hair cells. With the aim of developing new strategies for attenuating gentamicin ototoxicity, the present study investigated the otoprotective mechanism of 2,3,4',5‑tetrahydroxystilbene‑2‑O‑β‑D-glucoside (THSG) in vitro using the mouse cochlear cell line UB/OC‑2. MTT assay demonstrated that gentamicin reduced UB/OC‑2 cell viability and western blotting showed that gentamicin upregulated autophagy‑related proteins, such as Beclin, autophagy related 5 and LC3‑II. THSG significantly attenuated gentamicin‑induced cytotoxicity, clearly reduced LDH release observed by LDH assay and decreased the expression of autophagy‑related proteins. Reverse‑transcription‑quantitative (RT‑q) PCR and western blotting showed that THSG against gentamicin‑induced autophagy via suppressing the expression of Sesn2, at both the mRNA and protein level and a possible involvement of AMP‑activated protein kinase (AMPK)/mTOR signaling response. Collectively, the present study demonstrated that THSG decreased gentamicin‑induced ototoxicity in UB/OC‑2 cochlear cells via the autophagic signaling in regulating Sesn2/AMPK/mTOR pathway. These results suggested that THSG might be a new therapeutic agent with the potential to attenuate gentamicin ototoxicity.

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