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

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

    Research output: Contribution to journalArticlepeer-review

    10 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 Dec 1

    Keywords

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

    ASJC Scopus subject areas

    • Surgery
    • Otorhinolaryngology

    Fingerprint

    Dive into the research topics of 'Protective effect of metformin on gentamicin-induced vestibulotoxicity in rat primary cell culture'. Together they form a unique fingerprint.

    Cite this