Evaluation and Prevention of Gentamicin-induced Vestibulotoxicity in Rabbits Using Off-Vertical Axis Rotation

Park, Hyun Min; Jeon, Sang Jun; Jeong, Shin Keun; Choi, Won il; Park, Byung Kuhn; Rhee, Chung Ku; Chang, Sun O

Abstract

BACKGROUND AND OBJECTIVES
The purposes of this study was to investigate the characteristics of gentamicin-induced vestibulotoxicity of s otolith organs by assessing the results of earth vertical and the off-vertical axis rotation tests with a morphologic study. MATERIALS AND METHODS: Rabbits were grouped into two groups, ototoxic and ototoxic prevention group. Vestibulotoxicity was induced by injecting gentamicin (GM) into the peritoneum. Prevention of the vestibulotoxicity was studied by injecting NMDA receptor inhibitors (MK-801), iron chelating agents (deferoxamine) peritonially, and osmotic pumps filled with neurotrophic factors (GDNF, BDNF), respectively. The animal rotation system was designed to rotate the animal sinusoidally or in velocity step (constant velocity) rotation. Off-vertical rotation was applied to evaluate the otolithic function. Scanning electron microscopy were examined for the structural changes of the otolithic organs. RESULTS AND CONCLUSIONS: GM-induced vestibulotoxicity was confirmed by gain decreasing in the earth vertical SHA rotation test and bias decreasing in the off-vertical rotation test. However, changes in modulation was not definite. Bilateral prevention of GM-induced vestibulotoxicity was confirmed by systemic injection of deferoxamine and MK-801, and characteristics of unilateral prevention was confirmed by local application of the neurotrophic factors using osmotic pumps. In the SEM study, the GM-induced hair cell damages of the vestibule were identified, which was prevented by the preventive drugs. The reduction of bias value without change of modulation was comparable with the reduction of gain in the earth vertical axis rotation after GM-induced vestibulotoxicity.