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5 "Ototoxicity"
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Original Articles
Inner ear uptake of fluorescent gentamicin in neonatal mice: an experimental animal study
Jihye Rhee, Dong Woo Nam, Sung Joong Moon, Ja-Won Koo
Res Vestib Sci. 2025;24(2):98-106.   Published online June 15, 2025
DOI: https://doi.org/10.21790/rvs.2025.012
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AbstractAbstract PDF
Objectives
This study aimed to investigate whether systemic administration of fluorescently labeled gentamicin (gentamicin-Texas Red, GTTR) results in differential inner ear uptake during postnatal maturation of the blood-labyrinth barrier (BLB) in neonatal mice.
Methods
Neonatal C57BL/6 mice were intraperitoneally injected with GTTR at postnatal day 7 (P7), 21 (P21), or 35 (P35). Cochlear and renal tissues were harvested 60 minutes after injection and examined via confocal microscopy. Fluorescence intensity of GTTR in cochlear structures—including marginal cells, strial tissues, basal cells, spiral ligament, and hair cells—was quantified using ImageJ. Renal proximal tubules served as systemic uptake controls.
Results
GTTR uptake was significantly higher in cochlear lateral wall structures and hair cells of P7 mice compared to P35 mice (p<0.01). No significant differences in fluorescence were observed in the renal proximal tubules across age groups. Mice injected with unconjugated Texas Red showed negligible fluorescence in all tissues, confirming specific uptake of GTTR.
Conclusions
Inner ear uptake of aminoglycosides is markedly increased prior to full maturation of the BLB in neonatal mice. These findings suggest that immature cochlear barriers in early postnatal stages may enhance aminoglycoside entry into sensory hair cells, highlighting the need for cautious use of these antibiotics in premature infants.
Effects of Intrabullar Gentamicin Application on Guinea Pig Vestibulo-Ocular Reflex
Ja Won Koo, Jae Jun Song, Sung Kwang Hong, Ji Soo Kim
J Korean Bal Soc. 2008;7(1):9-16.
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AbstractAbstract PDF
Background and Objectives: Unilateral vestibular loss can be induced by intratympanic gentamicin instillation. Despite accumulated reports on the morphologic changes after gentamicin treatment, there are limited reports regarding the effects of gentamicin ototoxicity on the vestibulo-ocular reflex (VOR), in especially unilateral vestibular deficit by local gentamicin instillation. Aim of this study is to provide the functional changes after local gentamicin application in guinea pigs. Materials and Methods: Ten white guinea pigs (5 each for control and gentamicin treatment group) were used. Following surgical exposure of the left bulla, 0.9% saline solution or 40 mg/ml of gentamicin soaking gelfoam were applied on the round window. Horizontal vestibulo-ocular reflex (hVOR) was tested during earth vertical axis (EVA) sinusoidal harmonic acceleration rotation at 4 frequencies (0.04, 0.08, 0.16 and 0.32 Hz, 60 deg/sec of peak velocity). In one gentamicin treated animal, hVOR was tested during step velocity off-vertical axis rotation (OVAR) to clockwise and counterclockwise direction (30° forward tilt from EVA with constant velocity of 100 deg/sec). Every test was repeated before treatment and at 2 days, 5 days and 7 days after treatment. Results: The hVOR gain was significantly lowered after gentamicin treatment at all tested frequencies (p<0.05), while the gain does not change over time in control animals. Loss of bias component was evident and some decrease of modulation component was observed in counter-clockwise (lesion side) rotation after gentamicin treatment. Conclusion: This study provides characteristics of hVOR during EVA rotation and OVAR in unilateral vestibular deficit animal model by intrabullar gentamicin application.
Case Report
Asymmetric Audiovestibular Dysfunction in Patients With Systemic Aminoglycoside Treatment
Jae Hong Park, Yoon Chan Rah, Ji Soo Kim, Ja Won Koo
Res Vestib Sci. 2013;12(2):62-66.
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AbstractAbstract PDF
Since the characteristics of aminoglycoside ototoxicity is typically bilaterally symmetric progression of cochlea-vestibular dysfunction, a unilateral involvement has rarely been reported. However, ototoxicity can be asymmetric or focal after systemic aminoglycoside treatment. The authors report 2 cases of asymmetric or focal audiovestibular deficits in patients treated with systemic aminoglycoside. In such cases, further investigations are also necessary to rule out other possible causes of unilateral sensorineural hearing loss such as cerebellopontine angle tumors.
Original Articles
Expression of Caveolin-1 in the Differentiated Vestibular Cell Line (UB/UE-1) after Gentamicin Toxicity
Byung Han Cho, Kyu Sung Kim, Min Wook Kim, Min Sun Kim, Byung Rim Park
J Korean Bal Soc. 2005;4(2):243-249.
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AbstractAbstract PDF
Background
and Objectives: The caveolin is known as a mediator of cell death or survival of injured cell and inhibitor of various signaling pathways. We examined expression of caveolin-1 involved by protein kinase A(PKA) signaling pathway in the differentiated mouse vestibular cell line(UB/UE-1) after gentamicin toxicity. Materials and Method: We observed caveolae in the vestibular hair cell of healthy guinea pig through electron microscope. UB/UE-1 cells were cultured at 95% CO2, 5% O2, 33℃ for 2days and at 95% CO2, 5% O2, 39℃ for 24 hours for differentiation. Cells were treated with 1 mM of gentamicin, 0.02 mM H89 (PKA inhibitor), and then incubated for 24 hours. Caveolin-1 expression was examined by western blot and PKA activity by PepTagⓇ assay.
Results
Caveolae were observed in the vestibular hair cell of healthy guinea pig by electron microscope. Caveolin-1 was expressed spontaneously in differentiated UB/UE-1 cells and increased after gentamicin treatment. PKA is overactivated by gentamicin treatment. The gentamicin induced caveolin-1 expression and PKA overactivation was inhibited by H89.
Conclusion
Our results indicate that gentamicin induced caveolin-1 expression is mediated by PKA signaling pathway. We conclude that the caveolae/caveolin through a PKA signaling pathway is the important mechanism of gentamicin induced ototoxicity.
Effect of Low Power Laser Irradiation on Gentamicin-Damaged Vestibular System in Guinea Pigs
Chung Ku Rhee, Myoung Chan Kim, Eun Seok Lim, Young Saeng Kim
J Korean Bal Soc. 2005;4(2):225-229.
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  • 3 Download
AbstractAbstract PDF
Background
and Objectives:The purpose of this study was to investigate the characteristics of gentamicin-induced vestibulotoxicity of otolith organs and preventive effect of low power laser to vestibulotoxicity by assessing the result of earth vertical and the off vertical axis rotation tests. Materials and Method: Twenty guinea pigs were grouped into two groups, laser and no laser group. Vestibulotoxicity was induced by intratympanic injection of gentamicin. Prevention of the vestibulotoxicity was studied by irradiation of low power laser. Off vertical axis rotation tilted 30 degree relative to the earth vertical axis was applied to evaluate the otolithic function.
Results
Gentamicin induced vestibulotoxicity was confirmed by gain decreasing in slow harmonic acceleration test and modulation decreasing in the off vertical axis rotation test. Prevention effect of low power laser to gentamicin induced vestibulotoxicity was confirmed by modulation maintaining in the off vertical axis rotation test and gain maintaining in the earth vertical axis rotation.

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