Article
Cell-specific distribution patterns after intratympanic application of gentamicin and doxycyclin within the guinea pig cochlea
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Published: | July 23, 2012 |
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Introduction:The main reason for inner ear damage might be based on an increase in reactive oxygen and/or nitrogen species. The aim of the present study was to identify those regions within the cochlea where the NO-producing agent gentamicin and the NO-repressing substance doxycyclin become located after intratympanic application.
Methods: Gentamicin or doxycyclin were injected on both sides into the middle ear of male guinea pigs (n = 24 and n = 3, respectively). The cochleae were removed 1, 2 and 7 days after gentamicin injection or 1, 6 and 24 h after doxycyclin application, transferred into fixative and embedded in paraffin. The distribution patterns of gentamicin and doxycyclin were determined by specific antibodies on semi-thin sections. The cellular staining intensities were quantified for seven cochlear regions after the various time points of incubation by computer-assisted programs.
Results: Gentamicin was identified in wide regions of the cochlea in all experimental groups but with cell-specific differences. An intense accumulation was observed within the spiral ligament, in the limbus-area and in hair cells, with the tendency of a decrease from the first to the third cochlea turn. The role of the modiolus and of the lateral wall is discussed in respect to possible routes of infiltration. Doxycyclin was preferentially located in the stria vascularis and in hair cells.
Conclusion: The accumulation of gentamicin identified in those cochlea regions which are responsible for potassium recycling might result in a local NO-increase leading finally to cochlear damage. The specific accumulation of doxycyclin in the stria vascularis and hair cells might prevent an NO up-regulation in stress situations in these areas and offers a promising approach for human medication in future.