Protective Effect of Metformin on Gentamicin-Induced Vestibulotoxicity in Rat Primary Cell Culture
- Authors
- Lee, Ji Young; Lee, Se Hee; Chang, Ji Won; Song, Jae-June; Jung, Hak Hyun; Im, Gi Jung
- Issue Date
- 12월-2014
- Publisher
- KOREAN SOC OTORHINOLARYNGOL
- Keywords
- Labyrinth vestibule; Gentamicins; Metformin; Reactive oxygen species; Calcium
- Citation
- CLINICAL AND EXPERIMENTAL OTORHINOLARYNGOLOGY, v.7, no.4, pp.286 - 294
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- CLINICAL AND EXPERIMENTAL OTORHINOLARYNGOLOGY
- Volume
- 7
- Number
- 4
- Start Page
- 286
- End Page
- 294
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/96593
- DOI
- 10.3342/ceo.2014.7.4.286
- ISSN
- 1976-8710
- Abstract
- Objectives. One 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. Methods. For 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. Results. Vestibular 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. Conclusion. Metformin 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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