The Ganglioside Monosialotetrahexosylganglioside Protects Auditory Hair Cells Against Neomycin-Induced Cytotoxicity Through Mitochondrial Antioxidation: An in vitro Study.

Yujin Li,Shou-Lin Wang,Ling Lu,Xia Gao,Yaoting Zhang,Chao Wang,Ao Li,Xin Jin

doi:10.3389/fncel.2021.751867

Abstract

Neomycin is a common ototoxic aminoglycoside antibiotic that causes sensory hearing disorders worldwide, and monosialotetrahexosylganglioside (GM1) is reported to have antioxidant effects that protect various cells. However, little is known about the effect of GM1 on neomycin-induced hair cell (HC) ototoxic damage and related mechanism. In this study, cochlear HC-like HEI-OC-1 cells along with whole-organ explant cultures were used to establish an in vitro neomycin-induced HC damage model, and then the apoptosis rate, the balance of oxidative and antioxidant gene expression, reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were measured. GM1 could maintain the balance of oxidative and antioxidant gene expression, inhibit the accumulation of ROS and proapoptotic gene expression, promoted antioxidant gene expression, and reduce apoptosis after neomycin exposure in HEI-OC-1 cells and cultured cochlear HCs. These results suggested that GM1 could reduce ROS aggregation, maintain mitochondrial function, and improve HC viability in the presence of neomycin, possibly through mitochondrial antioxidation. Hence, GM1 may have potential clinical value in protecting against aminoglycoside-induced HC injury.

Highlights

Sensorineural hearing loss is a common sensory disorder in humans
Our results suggest that GM1 protects HEI-OC-1 cells from neomycin-induced apoptosis
Ceramide is composed of long basic hydrophobic chains attached to fatty acids that are embedded in the lipid bilayer of the cell membrane and enhance the stability of the cell membrane structure

Summary

Introduction

Sensorineural hearing loss is a common sensory disorder in humans. Many factors, including viral infections, noise, and exposure to ototoxic drugs, can cause hair cell (HC) damage and induce hearing impairment (Sotoudeh, 2021). It is estimated that approximately one-quarter of people who are treated with aminoglycoside antibiotics will develop ototoxicity (Lopez-Novoa et al, 2011). These drugs still play a crucial role in the treatment of severe gramnegative bacterial infections and multidrug-resistant tuberculosis and are becoming more irreplaceable as microbial resistance to conventional antimicrobial agents increases (Germovsek et al, 2017). Previous studies have found that aminoglycoside drugs accumulate in mitochondria after entering HCs and that this can lead to disorders of mitochondrial metabolism, imbalanced expression of prooxidants (ALOX15) and antioxidants (GSR, SOD1, NQO1, GLRX), and the production of excessive reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) and hydroxyl radicals (OH) in cells. No ideal drug that is protective against ototoxicity has been identified for use in clinical practice (Guo et al, 2019)

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