Protective effect of metformin on gentamicin-induced vestibulotoxicity in rat primary cell culture

Ji Young Lee, Se Hee Lee, Ji Won Chang, Jae-Jun Song, Hak Hyun Jung, Gi Jung Im

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)286-294
Number of pages9
JournalClinical and Experimental Otorhinolaryngology
Volume7
Issue number4
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

Primary Cell Culture
Metformin
Gentamicins
Reactive Oxygen Species
Saccule and Utricle
Calcium
Auditory Hair Cells
Fura-2
Cytochromes c
Fluorescent Dyes
Hypoglycemic Agents
Permeability
Oxidative Stress

Keywords

  • Calcium
  • Gentamicins
  • Labyrinth vestibule
  • Metformin
  • Reactive oxygen species

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology

Cite this

Protective effect of metformin on gentamicin-induced vestibulotoxicity in rat primary cell culture. / Lee, Ji Young; Lee, Se Hee; Chang, Ji Won; Song, Jae-Jun; Jung, Hak Hyun; Im, Gi Jung.

In: Clinical and Experimental Otorhinolaryngology, Vol. 7, No. 4, 01.01.2014, p. 286-294.

Research output: Contribution to journalArticle

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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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