Article
Analysis of gentamicin uptake in the acutely isolated rat inner ear
Search Medline for
Authors
Published: | July 6, 2010 |
---|
Outline
Text
The mechanisms of the beneficial effects of low dose intratympanal gentamcin in Meničre’s disease are still insufficiently understood.
Here we investigate which cells of the inner ear accumulate gentamicin and might thus be the target of this therapy.
Acutely isolated rat cochleae were incubated in DMEM supplemented with texas-red conjugated gentamicin for 10 minutes. The contralateral ear served as control group. Based on the model calculations of Salt et al. [1] we chose concentrations of 500 and 2500 µg/ml. After incubation, fixation and further histological processing frozen sections were used for the analysis.
At 500 µg/ml gentamicin non cellular structures such as basilar membrane, lining of perilymphatic spaces and the osseous spiral lamina showed a clear accumulation of gentamicin. Visual inspection of the sections indicated that an accumulation of gentamicin in cellular structures was limited to some interdental cells of the spiral limbus and a few inner hair cells. In outer hair cells no gentamicin accumulation was visible. At 2500 µg/ml the uptake of gentamicin in the cochlea appeared more widespread, especially inner as well as outer hair cells showed a clear accumulation of gentamicin.
In the vestibular epithelia no specific accumulation was seen at of 500 µg/ml. At 2500 µg/ml some uptake of gentamicin occurred but appeared less compared the cochlea.
These results suggest that gentamicin exposure leads to more pronounced accumulation in the cochlea than in vestibular epithelia. Based on the specific accumulation of gentamicin in interdental cells and inner hair cells at a low dose we propose the hypothesis that gentamicin may interact with the K±flow from the inner hair cells back to scala media (Spicer and Schulte 1998).
References
- 1.
- Salt AN, Gill RM, Plontke SK. Dependence of hearing changes on the dose of intratympanically applied gentamicin: a meta-analysis using mathematical simulations of clinical drug delivery protocols. Laryngoscope. 2008;118(10):1793-800. DOI: 10.1097/MLG.0b013e31817d01cd