Protective role of antidiabetic drug metformin against gentamicin induced apoptosis in auditory cell line

Jung, Hak Hyun; Chang, Jiwon; Yang, Ji Hyuk; Choi, June; Im, Gi Jung; Chae, Sung Won

doi:10.1016/j.heares.2011.09.005

Cited by 44 publications

(34 citation statements)

References 26 publications

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“…The optical density was measured using a microplate reader at 540 nm (Spectra Max; Molecular Devices, Sunnyvale, CA, USA). Results were from 5 separate experiments in triplicate [24,25,26]. …”

Section: Methodsmentioning

confidence: 99%

Protective Effect of Metformin on Gentamicin-Induced Vestibulotoxicity in Rat Primary Cell Culture

Lee

Chang

et al. 2014

Clin Exp Otorhinolaryngol

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ObjectivesOne of the antidiabetic drugs, metformin, have shown that it prevented oxidative stress-induced death in several cell types through a mechanism involving the opening of the permeability transition pore and cytochrome c release. Thus, it is possible that the antioxidative effect of metformin can also serve as protection against gentamicin-induced cytotoxicity related to reactive oxygen species (ROS). The aim of this study was to examine the protective effect of metformin on gentamicin-induced vestibulotoxicity in primary cell culture derived from rat utricle.MethodsFor vestibular primary cell culture, rat utricles were dissected and incubated. Gentamicin-induced cytotoxicity was measured in both the auditory and vestibular cells. To examine the effects of metformin on gentamicin-induced cytotoxicity in the primary cell culture, the cells were pretreated with metformin at a concentration of 1 mM for 24 hours, and then exposed to 2.5 mM gentamicin for 48 hours. The intracellular ROS level was measured using a fluorescent dye, and also measured using a FACScan flow cytometer. Intracellular calcium levels in the vestibular cells were measured with calcium imaging using Fura-2 AM.ResultsVestibular cells were more sensitive to gentamicin-induced cytotoxicity than auditory hair cells. Metformin protects against gentamicin-induced cytotoxicity in vestibular cells. Metformin significantly reduced a gentamicin-induced increase in ROS, and also reduced an increase in intracellular calcium concentrations in gentamicin-induced cytotoxicity.ConclusionMetformin significantly reduced a gentamicin-induced increase in ROS, stabilized the intracellular calcium concentration, and inhibited gentamicin-induced apoptosis. Thus, Metformin showed protective effect on gentamicin-induced cytotoxicity in vestibular primary cell culture.

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Section: Methodsmentioning

confidence: 99%

Protective Effect of Metformin on Gentamicin-Induced Vestibulotoxicity in Rat Primary Cell Culture

Lee

Chang

et al. 2014

Clin Exp Otorhinolaryngol

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“…Metformin 100 μM Metformin 1 mM Interestingly, Jung et al [2011] not only demonstrated in HEI-OC1 cell culture that metformin-pretreated cells produce fewer ROS than cells treated with gentamicin alone, but also showed that metformin inhibited the increase in intracellular calcium. It has been proposed that calcium retention modulates mitochondrial permeability transition that prevents cell death due to permeability transition pore-related cytochrome c release [Guigas et al, 2004;Lablanche et al, 2011].…”

Section: Controlmentioning

confidence: 97%

“…Our findings are in line with data obtained in auditory cell lines. Jung et al [2011] showed that metformin protects auditory cell lines against gentamicin-induced apoptosis. How can the protective effect of metformin in gentamicin-induced HC loss be explained?…”

Section: Metformin Protects Hcs From Gentamicin-induced Toxicitymentioning

confidence: 99%

“…It has been proposed that calcium retention modulates mitochondrial permeability transition that prevents cell death due to permeability transition pore-related cytochrome c release [Guigas et al, 2004;Lablanche et al, 2011]. Therefore, Jung et al [2011] proposed that the protective effect of metformin on gentamicin-induced HC toxicity is due to the calciummodulating and antiapoptotic effect of metformin. It should be noted that in our experiments cochlear explants were harvested from postnatal day 5 animals since only newborn animals can be used for extended culture of IHCs.…”

Section: Controlmentioning

confidence: 99%

“…The authors hypothesized that AMPK is positioned to play a role in cell regeneration and antiaging effects in the inner ear. Jung et al [2011] observed that metformin protects an auditory cell line against gentamicin-induced apoptosis. Recently, Chang et al [2014] showed that metformin had a protective effect against cisplatin-induced ototoxicity in an auditory cell line.…”

Section: Introductionmentioning

confidence: 99%

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Metformin Protects Auditory Hair Cells from Gentamicin-Induced Toxicity in vitro

Glutz¹,

Leitmeyer²,

Setz³

et al. 2015

Audiol Neurotol

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Metformin is a commonly used antidiabetic drug. It has been shown that this drug activates the AMP-activated protein kinase, which inhibits downstream the mammalian target of rapamycin. In addition, several studies indicate that metformin reduces intracellular reactive oxygen species. Our data, using an in vitro rat model, indicate that metformin is able to protect auditory hair cells (HCs) from gentamicin-induced apoptotic cell death. Moreover, metformin has no toxic effect on spiral ganglion neuronal survival or outgrowth in vitro. These results suggest a protective effect of metformin on auditory HC survival in gentamicin-induced HC loss in vitro.

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Protective role of edaravone against neomycin‐induced ototoxicity in zebrafish

Choi

Chang

Jun

et al. 2013

J of Applied Toxicology

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Aminoglycosides such as neomycin are one of the most commonly prescribed types of antibiotics worldwide. However, these drugs appear to generate free radicals within the inner ear, which can result in permanent hearing loss. We evaluated the effects of edaravone, a neuroprotective agent, on neomycin-induced ototoxicity in transgenic zebrafish. The 5-day post fertilization (dpf) zebrafish larvae were exposed to 125 μM neomycin and various concentrations of edaravone for 1 h. Hair cell survival was calculated as average numbers of the hair cells in the control group, which was not exposed to neomycin. Ultrastructural changes were evaluated using a scanning electron microscope (SEM) and transmission electron microscope (TEM). Edaravone protected against neomycin-induced hair cell loss in the neuromasts (1000 μM: 11.6 ± 1.1 cells, neomycin only: 5.5 ± 0.5 cells; n = 10, P<0.05) and decreased the TUNEL reaction for detecting apoptosis. In ultrastructural analysis, structures of mitochondria and hair cells within neuromasts were preserved in zebrafish exposed to 125 μM neomycin and 1000 μM edaravone for 1 h. Edaravone protected against neomycin-induced hair cell loss by preventing apoptosis.

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Protective role of antidiabetic drug metformin against gentamicin induced apoptosis in auditory cell line

Cited by 44 publications

References 26 publications

Protective Effect of Metformin on Gentamicin-Induced Vestibulotoxicity in Rat Primary Cell Culture

Protective Effect of Metformin on Gentamicin-Induced Vestibulotoxicity in Rat Primary Cell Culture

Metformin Protects Auditory Hair Cells from Gentamicin-Induced Toxicity in vitro

Protective role of edaravone against neomycin‐induced ototoxicity in zebrafish

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