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A systemic gentamicin pathway across the stria vascularis.
1Oregon Hearing Research Center, Oregon Health Sciences University, Portland, OR 97239, USA.
Hearing Research
|December 18, 2007
Summary
Systemic aminoglycoside entry into the cochlea is unclear. Gentamicin competitively inhibits fluorescent gentamicin uptake in hair and marginal cells, suggesting a barrier to cochlear entry.
Area of Science:
- Ototoxicity and inner ear drug delivery
- Pharmacokinetics and molecular mechanisms
Background:
- Systemic aminoglycoside cochlear entry mechanisms are not well understood.
- Aminoglycosides are crucial antibiotics but can cause hearing loss.
Purpose of the Study:
- To investigate the mechanisms of systemically administered aminoglycosides entering the cochlea.
- To determine if gentamicin uptake is competitively inhibited in different cochlear compartments.
Main Methods:
- Co-administration of gentamicin and fluorescent gentamicin (GTTR) in mice at varying molar ratios and doses.
- Confocal microscopy examination of cochleae three hours post-administration.
- Analysis of GTTR fluorescence intensity in hair cells, marginal cells, and strial tissues.
Main Results:
- Increasing gentamicin doses with a constant gentamicin:GTTR ratio increased GTTR fluorescence.
- Decreasing GTTR concentration with a fixed gentamicin dose reduced fluorescence in hair cells and stria.
- Gentamicin competitively inhibited GTTR uptake in hair and marginal cells, but not in strial capillaries.
Conclusions:
- Gentamicin uptake in cochlear hair and marginal cells is competitively inhibited.
- A regulatable barrier likely exists for gentamicin entry into the endolymph.
- This barrier is located between marginal cells, the intra-strial space, and intermediate cells.
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