(-)-Epigallocatechin-3-gallate (EGCG) prevents aminoglycosides-induced ototoxicity via anti-oxidative and anti-apoptotic pathways

Copyright © 2021 Elsevier B.V. All rights reserved..

OBJECTIVES: Aminoglycoside-induced cochlear ototoxicity causes inner ear hair cells (HCs) loss and leads to hearing impairment in patients, but no treatment completely eliminates the ototoxic effect. This study aims to determine the effectiveness of (-)-Epigallocatechin-3-gallate (EGCG) as a protective agent against aminoglycoside-induced ototoxicity.

METHODS: Zebrafish were exposed to EGCG for 24 h and then co-treated with EGCG and ototoxic agent (amikacin and gentamicin) for 5 h to explore the protective effect of EGCG on zebrafish HCs. Network pharmacology analysis and molecular docking simulation were conducted to explore its potential mechanism, and in vitro cell experiments were used to validate the outcome of the result.

RESULT: EGCG against ototoxicity of aminoglycosides in zebrafish HCs. Network pharmacology analysis and molecular docking showing that molecules related to cellular response regulation to oxidative stress, including AKT1, DHFR, and MET, may be the target proteins of EGCG, which were verified in vitro experiments. Further experiments demonstrated thatEGCG can antagonize the death of HCs caused by amikacin and gentamicin by reducing intracellular reactive oxygen species (ROS) accumulation and anti-apoptosis.

CONCLUSION: EGCG can be an otoprotective drug against aminoglycosides-induced ototoxicity, prevent cellular apoptosis and significantly reduce oxidative stress.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:150

Enthalten in:

International journal of pediatric otorhinolaryngology - 150(2021) vom: 30. Nov., Seite 110920

Sprache:

Englisch

Beteiligte Personen:

Zong, Yulong [VerfasserIn]
Chen, Fang [VerfasserIn]
Li, Shanshan [VerfasserIn]
Zhang, Hui [VerfasserIn]

Links:

Volltext

Themen:

(−)-Epigallocatechin-3-gallate
8R1V1STN48
Amikacin
Aminoglycosides
BQM438CTEL
Catechin
Epigallocatechin gallate
Gentamicin
Journal Article
Ototoxicity
Pharmaceutical Preparations
Reactive Oxygen Species
Reactive oxygen species

Anmerkungen:

Date Completed 02.11.2021

Date Revised 02.11.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.ijporl.2021.110920

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM330426141