The protective effect of metformin against the noise-induced hearing loss

Kesici, Gülin Gökçen; Öçal, Fatma Ceyda Akın; Gürgen, Seren Gülşen; Erdem, Remzi; Öğüş, Ersin; Erbek, Seyra; Özlüoğlu, Levent N.

doi:10.1007/s00405-018-5161-7

Cited by 14 publications

(14 citation statements)

References 25 publications

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“…By intersecting the noise-induced gene expression changes in our combined datasets with DrugCentral (Ursu et al, 2017), we identified metformin as the top-ranking candidate therapeutic (Table S7). Indeed, metformin has been previously shown to reduce the severity of NIHL in a rat model (Kesici et al, 2018), has shown promise in prevention of ototoxicity in vitro (Oishi et al, 2014), and was shown in diabetic patients to be associated with decreased risk for sudden sensorineural hearing loss (Chen et al, 2019). Interestingly, the cholesterol lowering drugs, statins, which target HMG-CoA reductase (an indirect target of metformin), were also identified in our data as a candidate therapeutic for NIHL.…”

Section: Discussionmentioning

confidence: 55%

A cell-type-specific atlas of the inner ear transcriptional response to acoustic trauma

Milon

Shulman

et al. 2021

Cell Reports

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Section: Discussionmentioning

confidence: 55%

A cell-type-specific atlas of the inner ear transcriptional response to acoustic trauma

Milon

Shulman

et al. 2021

Cell Reports

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“…Recently, researchers identified metformin as the top-ranking candidate therapeutic for NIHL when conducting virtual drug screening via cochlear single-cell sequencing ( Milon et al, 2021 ). Previous studies ( Kesici et al, 2018 ; Gedik et al, 2020 ) have shown that metformin protects against noise damage by inhibiting oxidative stress and hair cell apoptosis. However, according to a recently published study of type 2 diabetes mellitus treated with metformin, in the peripheral blood of the metformin treatment group, the expression of leukocyte mitochondrial fusion proteins MFN1/2 and OPA1 increased, the level of mitochondrial fission proteins DRP1 and FIS1 decreased, and the mitochondrial ROS levels were lower than that of the control group.…”

Section: Abnormal Mitochondrial Dynamics and Hearing Lossmentioning

confidence: 93%

“…There are currently no medications approved for the treatment of hearing loss, but some drugs, such as melatonin ( Serra et al, 2020 ) and metformin ( Kesici et al, 2018 ), have demonstrated efficacy in many animal models of hearing loss. Melatonin is a hormone secreted by the pineal gland that targets mitochondria to exert its neuroprotective effects.…”

Section: Abnormal Mitochondrial Dynamics and Hearing Lossmentioning

confidence: 99%

Impacts of impaired mitochondrial dynamics in hearing loss: Potential therapeutic targets

Zou

Chen

et al. 2022

Front. Neurosci.

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Mitochondria are the powerhouse of the cells. Under physiological conditions, mitochondrial fission and fusion maintain a dynamic equilibrium in the cytoplasm, which is referred to as mitochondrial dynamics. As an important approach to regulating mitochondrial function and quantity, the role of mitochondrial dynamics has been demonstrated in the pathogenesis of various disease models, including brain damage, neurodegeneration, and stress. As the vital organ of the peripheral auditory system, the cochlea consumes a significant amount of energy, and the maintenance of mitochondrial homeostasis is essential for the cochlear auditory capacity. OPA1 functions as both a necessary gene regulating mitochondrial fusion and a pathogenic gene responsible for auditory neuropathy, suggesting that an imbalance in mitochondrial dynamics may play a critical role in hearing loss, but relevant studies are few. In this review, we summarize recent evidence regarding the role of mitochondrial dynamics in the pathogenesis of noise-induced hearing loss (NIHL), drug-induced hearing loss, hereditary hearing loss, and age-related hearing loss. The impacts of impaired mitochondrial dynamics on hearing loss are discussed, and the potential of mitochondrial dynamics for the prevention and treatment of hearing loss is considered.

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“…Anti-inflammatory properties of metformin may in part be mediated by its ability to limit the production of reactive oxygen species by NADH:Ubiquinone Oxidoreductase, which may limit induction of pro-inflammatory interleukin-1β and boost anti-inflammatory interleukin-10 ( Kelly et al, 2015 ). Recently, metformin has been found to have some beneficial properties as it relates to hearing protection in preclinical and clinical studies against a variety of insults to the inner ear including radiation, noise, and cisplatin, as well as in the recovery of hearing in the setting of sudden sensorineural hearing loss ( Chang et al, 2014 ; Hosoya et al, 2017 ; Kesici et al, 2018 ; Chen et al, 2019 ; Muri et al, 2019 ; Feng et al, 2020 ). These observations suggest the possibility that metformin may have broader therapeutic applications as it relates to hearing.…”

Section: Discussionmentioning

confidence: 99%

Single-Cell RNA-Seq of Cisplatin-Treated Adult Stria Vascularis Identifies Cell Type-Specific Regulatory Networks and Novel Therapeutic Gene Targets

Taukulis

Olszewski

Korrapati

et al. 2021

Front. Mol. Neurosci.

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The endocochlear potential (EP) generated by the stria vascularis (SV) is necessary for hair cell mechanotransduction in the mammalian cochlea. We sought to create a model of EP dysfunction for the purposes of transcriptional analysis and treatment testing. By administering a single dose of cisplatin, a commonly prescribed cancer treatment drug with ototoxic side effects, to the adult mouse, we acutely disrupt EP generation. By combining these data with single cell RNA-sequencing findings, we identify transcriptional changes induced by cisplatin exposure, and by extension transcriptional changes accompanying EP reduction, in the major cell types of the SV. We use these data to identify gene regulatory networks unique to cisplatin treated SV, as well as the differentially expressed and druggable gene targets within those networks. Our results reconstruct transcriptional responses that occur in gene expression on the cellular level while identifying possible targets for interventions not only in cisplatin ototoxicity but also in EP dysfunction.

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The protective effect of metformin against the noise-induced hearing loss

Cited by 14 publications

References 25 publications

A cell-type-specific atlas of the inner ear transcriptional response to acoustic trauma

A cell-type-specific atlas of the inner ear transcriptional response to acoustic trauma

Impacts of impaired mitochondrial dynamics in hearing loss: Potential therapeutic targets

Single-Cell RNA-Seq of Cisplatin-Treated Adult Stria Vascularis Identifies Cell Type-Specific Regulatory Networks and Novel Therapeutic Gene Targets

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