Gentamicin administration leads to synaptic dysfunction in inner hair cells

Li, Gen; Gao, Yunge; Wu, Hao; Zhao, Ting

doi:10.1016/j.toxlet.2023.12.007

Cited by 3 publications

(1 citation statement)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The concept of synaptopathy was introduced when studies demonstrated reduced wave 1 of ABR in mice with histologically confirmed synapse loss following noise exposure [ 28 ]. Subsequent research in other rodent species [ 29 ] and primates [ 30 ] supported this concept, while additional studies suggested associations with age [ 31 ] and drug ototoxicity [ 32 , 33 ]. Another frequently used measure in researching SNHL in animal models is distortion-product otoacoustic emissions (DPOAEs), emissions produced by the outer hair cells (OHCs) of the inner ear in response to tones [ 34 – 38 ] ( Fig 2 ).…”

Section: Introductionmentioning

confidence: 99%

Diabetes mellitus, hearing loss, and therapeutic interventions: A systematic review of insights from preclinical animal models

Mittal,

Keith,

Lacey

et al. 2024

PLoS ONE

View full text Add to dashboard Cite

Objectives The aim of this systematic review article is to evaluate the relationship between diabetes mellitus (DM) and sensorineural hearing loss (SNHL) utilizing preclinical animal models. The review focused on studies assessing SNHL in diabetic animal models, elucidating the mechanisms of DM-associated SNHL, and exploring the response of diabetic animal models to noise overexposure. We also discussed studies investigating the efficacy of potential therapeutic strategies for amelioration of DM-associated SNHL in the animal models. Methods A protocol of this systematic review was designed a priori and was registered in the PROSPERO database (registration number: CRD42023439961). We conducted a comprehensive search on PubMed, Science Direct, Web of Science, Scopus, and EMBASE databases. A minimum of three reviewers independently screened, selected, and extracted data. The risk of bias assessment of eligible studies was conducted using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool. Results Following the screening of 238 studies, twelve original articles were included in this systematic review. The studies revealed that hyperglycemia significantly affects auditory function, with various pathological mechanisms contributing to DM-induced hearing impairment, including cochlear synaptopathy, microangiopathy, neuropathy, oxidative stress, mitochondrial abnormalities, and apoptosis-mediated cell death. Emerging interventions, such as Asiaticoside, Trigonelline, Chlorogenic acid, and Huotanquyu granules, demonstrated efficacy in providing otoprotection for preserving cochlear hair cells and hearing function. Conclusions Our systematic review delves into the intricate relationship between DM and hearing impairment in animal models. Future research should focus on targeted therapies to enhance cochlear mitochondrial function, alleviate oxidative stress, and regulate apoptosis. The association between SNHL and social isolation as well as cognitive decline underscores the necessity for innovative therapeutic modalities addressing yet undiscovered mechanisms. Translating findings from animal models to human studies will validate these findings, offering a synergistic approach to effectively manage DM-associated co-morbidities such as hearing impairment.

show abstract

Section: Introductionmentioning

confidence: 99%

Diabetes mellitus, hearing loss, and therapeutic interventions: A systematic review of insights from preclinical animal models

Mittal,

Keith,

Lacey

et al. 2024

PLoS ONE

View full text Add to dashboard Cite

show abstract

Impact of repeated intranasal gentamicin irrigation on auditory brainstem evoked potentials in rats

Mansour,

Haddad,

Breeden

et al. 2024

Exp Brain Res

View full text Add to dashboard Cite

Piplartine attenuates aminoglycoside-induced TRPV1 activity and protects from hearing loss in mice

Zallocchi,

Vijayakumar,

Fleegel

et al. 2024

Sci. Transl. Med.

View full text Add to dashboard Cite

Hearing loss is a major health concern in our society, affecting more than 400 million people worldwide. Among the causes, aminoglycoside therapy can result in permanent hearing loss in 40% to 60% of patients receiving treatment, and despite these high numbers, no drug for preventing or treating this type of hearing loss has yet been approved by the US Food and Drug Administration. We have previously conducted high-throughput screenings of bioactive compounds, using zebrafish as our discovery platform, and identified piplartine as a potential therapeutic molecule. In the present study, we expanded this work and characterized piplartine’s physicochemical and therapeutic properties. We showed that piplartine had a wide therapeutic window and neither induced nephrotoxicity in vivo in zebrafish nor interfered with aminoglycoside antibacterial activity. In addition, a fluorescence-based assay demonstrated that piplartine did not inhibit cytochrome C activity in microsomes. Coadministration of piplartine protected from kanamycin-induced hair cell loss in zebrafish and protected hearing function, outer hair cells, and presynaptic ribbons in a mouse model of kanamycin ototoxicity. Last, we investigated piplartine’s mechanism of action by phospho-omics, immunoblotting, immunohistochemistry, and molecular dynamics experiments. We found an up-regulation of AKT1 signaling in the cochleas of mice cotreated with piplartine. Piplartine treatment normalized kanamycin-induced up-regulation of TRPV1 expression and modulated the gating properties of this receptor. Because aminoglycoside entrance to the inner ear is, in part, mediated by TRPV1, these results suggested that by regulating TRPV1 expression, piplartine blocked aminoglycoside’s entrance, thereby preventing the long-term deleterious effects of aminoglycoside accumulation in the inner ear compartment.

show abstract

Gentamicin administration leads to synaptic dysfunction in inner hair cells

Cited by 3 publications

References 72 publications

Diabetes mellitus, hearing loss, and therapeutic interventions: A systematic review of insights from preclinical animal models

Diabetes mellitus, hearing loss, and therapeutic interventions: A systematic review of insights from preclinical animal models

Impact of repeated intranasal gentamicin irrigation on auditory brainstem evoked potentials in rats

Piplartine attenuates aminoglycoside-induced TRPV1 activity and protects from hearing loss in mice

Contact Info

Product

Resources

About