Ototoxic mechanisms: A Working Hypothesis

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Abstract
The effect of the ototoxic aminoglycosidic antibiotics, including neomycin, gentamicin and other members of the streptomycin family, on the internal ear is well known. In the cochlea, it has been generally interpreted as a direct toxic action on the sensory cells of the spiral organ. Measurements of antibiotic levels in the internal ear fluids have indicated a gradual build-up of concentrations that persist for some time after the plasma level has fallen to zero. The existence of a 'blood-ear' (hemato-laby-rinthine) barrier is suggested, corresponding to but less effective than the blood-brain barrier. The barrier must depend, inter alia, upon the integrity of the spiral ligament and the stria vascularis and their microvaculature. Evidence is presented to show that the aminoglycosides damage these 'secretory' tissues as well as those of the spiral prominence and outer sulcus, which are believed to be reabsorptive in function. The ototoxic process is thought to correspond to the nephrotoxic action, which occurs mainly in the renal tubules. Injury to the sensory cells is regarded as secondary to the disruption of the micro-homeostatic mechanism of the cochlea which maintain the appropriate concentrations of sodium and potassium ions in the endolymph and perilymph. The aminoglycosidic antibiotics are presumably bound to the proteins of the tissues affected, but understanding of the nature of the metabolic reactions inhibited remains for future cytochemical research.