Therapeutic effects of metformin for noise induced hearing loss

Gedik, Özge; Doğan, Remzi; Babademez, Mehmet Alı; Karataş, Ersin; Aydın, Mehmet; Koçyiğit, Abdürrahim; Eşrefoğlu, Mukaddes; Özturan, Orhan

doi:10.1016/j.amjoto.2019.102328

Cited by 15 publications

(18 citation statements)

References 20 publications

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“…Recently, researchers identified metformin as the topranking 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: Drugs Treat Hearing Loss By Modulating Mitochondrial Dynamicsmentioning

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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Section: Drugs Treat Hearing Loss By Modulating Mitochondrial Dynamicsmentioning

confidence: 99%

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

Zou

Chen

et al. 2022

Front. Neurosci.

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“…After noise exposure, the number and activation of inflammation-related cells in the cochlea are increased, along with an increase in the expression of inflammatory cytokines, which cause damage to the OHCs . In addition, overproduction of ROS in NIHL may have generated proinflammatory cytokines, which further aggravate inflammation in the cochlea. − To test the anti-inflammatory ability of PL-PPS/BBR, we detected TNF-α, IL-6, and IL-1, which represent the severity of the inflammation induced by noise.…”

Section: Resultsmentioning

confidence: 99%

ROS-Responsive Nanoparticle as a Berberine Carrier for OHC-Targeted Therapy of Noise-Induced Hearing Loss

Zhao

Han

Naveena

et al. 2021

ACS Appl. Mater. Interfaces

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Overproduction of reactive oxygen species (ROS) and inflammation are two key pathogeneses of noise-induced hearing loss (NIHL), which leads to outer hair cell (OHC) damage and hearing loss. In this work, we successfully developed ROS-responsive nanoparticles as berberine (BBR) carriers (PL-PPS/BBR) for OHC-targeted therapy of NIHL: Prestin-targeting peptide 2 (PrTP2)-modified nanoparticles (PL-PPS/BBR), which effectively accumulated in OHC areas, and poly(propylene sulfide) 120 (PPS 120 ), which scavenged ROS and converted to poly(propylene sulfoxide) 120 in a ROS environment to disintegrate and provoke the rapid release of BBR with anti-inflammatory and antioxidant effects. In this study, satisfactory anti-inflammatory and antioxidant effects of PL-PPS/BBR were confirmed. Immunofluorescence and scanning electron microscopy (SEM) images showed that PL-PPS/BBR effectively accumulated in OHCs and protected the morphological integrity of OHCs. The auditory brainstem response (ABR) results demonstrated that PL-PPS/BBR significantly improved hearing in NIHL guinea pigs after noise exposure. This work suggested that PL-PPS/BBR may be a new potential treatment for noise-associated injury with clinical application.

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“…It protected against gentamicin [154] and cisplatin [155,156] ototoxicity in an auditory cell line and against gentamicin-induced hair cell death in cochlear explants in vitro [157,158]. Metformin was also otoprotective in vivo against noise-induced hearing loss [159], cisplatin-induced hearing loss [156], pneumococcal meningitis-induced hearing loss [160], but not against gentamicin-induced hearing loss in guinea pigs [158].…”

Section: Mtor Signaling In Auditory Sensory Hair Cell Survival and Deathmentioning

confidence: 97%

mTOR Signaling in the Inner Ear as Potential Target to Treat Hearing Loss

Cortada

Levano

Bodmer

2021

IJMS

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Hearing loss affects many people worldwide and occurs often as a result of age, ototoxic drugs and/or excessive noise exposure. With a growing number of elderly people, the number of people suffering from hearing loss will also increase in the future. Despite the high number of affected people, for most patients there is no curative therapy for hearing loss and hearing aids or cochlea implants remain the only option. Important treatment approaches for hearing loss include the development of regenerative therapies or the inhibition of cell death/promotion of cell survival pathways. The mammalian target of rapamycin (mTOR) pathway is a central regulator of cell growth, is involved in cell survival, and has been shown to be implicated in many age-related diseases. In the inner ear, mTOR signaling has also started to gain attention recently. In this review, we will emphasize recent discoveries of mTOR signaling in the inner ear and discuss implications for possible treatments for hearing restoration.

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Therapeutic effects of metformin for noise induced hearing loss

Cited by 15 publications

References 20 publications

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

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

ROS-Responsive Nanoparticle as a Berberine Carrier for OHC-Targeted Therapy of Noise-Induced Hearing Loss

mTOR Signaling in the Inner Ear as Potential Target to Treat Hearing Loss

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