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Protective effect of metformin on gentamicin-induced vestibulotoxicity in rat primary cell culture
Ji Young Lee1, Se Hee Lee1, Ji Won Chang1
1Department of Otolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea.
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.
Insights
Metformin protects vestibular cells from gentamicin-induced damage by reducing reactive oxygen species (ROS) and stabilizing calcium levels. This study demonstrates metformin
Area of Science:
- Ototoxicity research
- Cellular toxicology
- Pharmacology
Background:
- Metformin, an antidiabetic drug, prevents oxidative stress-induced cell death.
- Gentamicin causes cytotoxicity via reactive oxygen species (ROS).
Purpose of the Study:
- To investigate metformin's protective effects against gentamicin-induced vestibulotoxicity.
- To assess metformin's impact on ROS and calcium levels in rat utricle cell cultures.
Main Methods:
- Primary cell cultures from rat utricles were established.
- Cells were pretreated with metformin then exposed to gentamicin.
- Intracellular ROS and calcium levels were measured.
Main Results:
- Vestibular cells showed higher sensitivity to gentamicin than auditory cells.
- Metformin significantly reduced gentamicin-induced ROS and intracellular calcium increases.
- Metformin demonstrated a protective effect against gentamicin cytotoxicity.
Conclusions:
- Metformin mitigates gentamicin-induced cytotoxicity in vestibular cells.
- It reduces ROS, stabilizes intracellular calcium, and inhibits apoptosis.
- Metformin offers a potential protective strategy against gentamicin ototoxicity.
