ABSTRACT
OBJECTIVE: To assess the ototoxicity of commercially available Gentacidin and TobraDex ear drops with and without liver extract activation using isolated cochlear outer hair cells (OHCs). MATERIAL AND METHODS: OHCs from adult chinchilla cochleae were exposed to standard bathing solution (SBS), liver extract alone and Gentacidin and TobraDex ear drops with and without liver extract. All experiments were performed at an osmolality of 305 +/-5 mOsm, at room temperature and for up to 60 min. OHC images were recorded using an inverted microscope and analyzed electronically. Time to cell death and changes in cell length were measured. RESULTS: The time to cell death and the percent change in cell length were significantly shorter in the Gentacidin+liver extract group than in the Gentacidin alone group (p < 0.05). The TobraDex+liver extract group showed a significantly decreased time to cell death compared to the SBS control group (p < 0.05). There were no significant differences in cell length or time to cell death between the TobraDex+liver extract group and the TobraDex alone group (p > 0.05). CONCLUSION: This study suggests that the cytotoxicity of aminoglycoside ear drops to isolated OHCs in vitro requires
Subject(s)
Aminoglycosides/toxicity , Anti-Bacterial Agents/toxicity , Gentamicins/toxicity , Hair Cells, Auditory, Outer/drug effects , Liver Extracts/pharmacology , Tobramycin/toxicity , Animals , Cell Death/drug effects , Cell Size/drug effects , Chinchilla , In Vitro TechniquesABSTRACT
OBJECTIVES: Otic drops are commonly used not only for otitis externa but also for otorrhea in the presence of tympanic membrane perforation or tympanostomy tube. Many studies demonstrated the ototoxicity of aminoglycoside. In our previous study, we observed that gentamicin (GM), when activated with liver extract, demonstrated significant cytotoxicity. The purpose of this study was to assess the protective effect of corticosteroid against the cytotoxicity of GM and tobramycin drops using isolated cochlear outer hair cells (OHCs) in vitro with liver extract. METHODS: OHCs from adult chinchilla cochleae were exposed to standard bathing solution, liver extract alone, and aminoglycoside otic drops with and without corticosteroid and liver extract. All experiments were performed at an osmolality of 305 +/- 5 mOsm, at room temperature, and for up to 60 minutes. The images of OHCs were recorded using an inverted microscope and analyzed on the Image Pro-Plus 3.0 program. Time to cell death and change of cell length were measured and analyzed. RESULTS: The time to cell death and percent change in cell length observed was significantly longer in the GM + liver extract + dexamethasone group than the GM + liver extract group (P <.05). The Tobradex + liver extract group showed an insignificant increase in percent change of cell length (P >.05) and significantly increased time to cell death than the tobramycin + liver extract group (P <.05). CONCLUSION: This study demonstrated that dexamethasone significantly reduced aminoglycoside cytotoxicity.
Subject(s)
Aminoglycosides/adverse effects , Anti-Inflammatory Agents/therapeutic use , Cerebrospinal Fluid Otorrhea/drug therapy , Dexamethasone/therapeutic use , Hair Cells, Auditory, Outer/drug effects , Tobramycin/adverse effects , Tympanic Membrane Perforation/drug therapy , Aminoglycosides/metabolism , Animals , Anti-Inflammatory Agents/pharmacology , Cell Death/drug effects , Chinchilla , Dexamethasone/pharmacology , Drug Therapy, Combination , Tobramycin/metabolismABSTRACT
OBJECTIVE: The purpose of this study was to determine the role of nitric oxide (NO) in the pathogenesis of mucoid otitis media (OM) in lipopolysaccharide (LPS)-induced OM. METHODS: OM was induced in chinchillas by injecting S-nitroso-N-acetylpenicillamine (SNAP), LPS, and LPS + SNAP into the superior bullae. Auditory brainstem response thresholds were measured every 24 hours. Samples of middle ear fluid were collected and analyzed for mucin by the periodic acid-Schiff method. At the end of each experiment, temporal bones were harvested for histopathologic study. RESULTS: Mucin concentration was greatest in the LPS + the SNAP group and least in the SNAP-alone group. Auditory brainstem response threshold was highest in the LPS group and lowest in the SNAP group, although not significantly. Histopathology showed the greatest mucosal thickening and inflammation in the LPS + SNAP group. CONCLUSION: The addition of NO in LPS-induced OM increased the mucin concentration in middle ear fluid and increased mucosal thickness and inflammation in middle ear mucosa. SIGNIFICANCE: In the OM disease process, NO may contribute to the pathogenesis of mucoid OM.