ABSTRACT
BACKGROUND AND OBJECTIVES: Gentamicin (GM) is well known for its vestibulotoxicity. There have been many reports about vestibulotoxicity, however, its mechanism is still unclear. So far, it is known that GM affects the voltage-dependent K+ current and nitric oxide (NO) production. Epigallocatechin-3-gallate (EGCG) is the major component of green tea and is known to have anti-oxidative and anti-toxic effect. This study was undertaken to investigate the protective effect of EGCG against gentamicin on vestibular hair cell (VHC). MATERIALS AND METHOD: White guinea pigs (200-250 g) were rapidly decapitated and the temporal bones were immediately removed. Under a dissecting microscope, the crista ampullaris was obtained. The dissociated VHCs were transferred into a recording chamber mounted onto an inverted microscope. Whole-cell membrane currents and potentials were recorded using standard patch-clamp techniques. In addition, measurements of NO production were obtained using the NO-sensitive dye, 4,5-diamino-fluorescein diacetate (DAF-2DA). RESULTS: Type I VHCs Voltage-dependent K+ current was activated from low depolarizing stimulation. As the stimulation increased, higher current was detected. Voltage-dependent K+ current in type I VHCs was decreased when GM (200 microM) was administrated and GM effects of K+ current inhibition was significantly blocked by EGCG. Extracellular GM-induced an increase in DAF-2DA fluorescence, which thus indicates NO production in VHCs. Also, the GMinduced NO production was inhibited by EGCG. CONCLUSION: GM inhibits voltage-dependent K+ current by releasing NO in isolated type I VHCs. EGCG blocks this inhibitory effects, suggesting a protective role on GM vestibulotoxicity.