Gentamicin uptake by cochlear hair cells precedes hearing impairment during chronic treatment

Immunodetection of gentamicin (GM) was carried out on surface preparations of the whole organ of Corti from cochleas of guinea pigs treated daily with GM at a dose of 60 mg/kg/day and sacrificed at the end of different treatment periods. Cochlear function was determined just before sacrifice, 24 h after the last injection. Threshold elevations, mainly at high frequencies, were noted only after 10-14 days of treatment. However, the presence of GM was observed much earlier, as early as after the second injection, and specifically in the sensory hair cells. GM labelling was essentially observed in the outer hair cells (OHC) and increased from the apex to the base of the cochlea and from the third to the first row of OHC. GM labelling of inner hair cells was less pronounced and was observed only after the 8th day of treatment. These observations demonstrate that GM specifically enters and accumulates in the sensory hair cells and that the uptake precedes the development of functional and cellular damage which may result from a long-term intracellular cytotoxic action of the molecule.