gms | German Medical Science

Objective: The therapeutic application of gentamicin generally induces numerous different, partly contrary, biochemical processes. Besides apoptosis and resulting cell death, there is some evidence for the induction of cell protecting mechanisms in which proteine kinase B (Akt) is involved. The aim of this study was to identify details about these gentamicin-induced processes in an animal model by evaluation of the spatial and temporal distribution patterns of Akt and its activated form (p-Akt).

Material and methods: Gentamicin (0.1 ml corresponding to 4 mg/ear/animal) was injected intratympanically into male guinea pigs (n=24). Auditory brainstem responses were recorded prior to and 1, 2 and 7 days after application. The cochlea was removed from its capsule, fixated and embedded in paraffin. Akt and p-Akt were localized by specific antibodies in semi-thin sections. Their staining intensities were quantified in seven cell types at the three time points using computer programs.

Results: The application of gentamicin resulted in an up-regulation of Akt-expression in the organ of Corti and the spiral ganglion cells. In other regions such as the stria vascularis, spiral ligament and interdental cells no alterations were found in the Akt-expression patterns. The expression of the phosphorylated form, p-Akt, was found to be increased only in two cell types in the organ of Corti, in Deiters’ cells and in pillar cells. Comparing both expression patterns, an increase in the Akt/p-Akt ratio was identified in inner and outer hair cells and in spiral ganglion cells.

Conclusion: The findings demonstrate a substantial up-regulation of Akt in the inner ear and only a limited increase in its activity. Based on this finding, cell-specific differences are discussed in view of the toxic effects of gentamicin.