Blood-perilymph barrier and ototoxicity: An in vivo study in the rat

Cisplatin and gentamicin are two ototoxicants that are supposed to be trans ported by the paracellar route, i.e. via cellular junctions, to the perilym phatic compartment. This study was initiated to test the hypothesis that su sceptive variation of individuals to ototoxic drugs may be explained by var iability in transport properties. The transport of radioactive mannitol thr ough the blood-perilymph barrier was correlated in vivo with the acute effe ct of cisplatin and gentamicin on auditory function. Transport of radioacti ve mannitol across the blood-perilymph barrier was monitored by sampling of scala vestibuli perilymph at 60 and 120 min after an intravenous infusion of the tracer to nephrectomized Long Evans rats. Counting of hair cell loss was performed in the animals receiving 16 mg/kg body weight cisplatin. The transport of radioactive mannitol across the blood-perilymph barrier did n ut correlate with the ototoxic effect of cisplatin, evaluated as changes in the auditory-evoked brainstem response thresholds or loss of outer hair ce lls. The results provide evidence that the barrier function is not involved in the interindividual variability of the ototoxic effect of cisplatin. Fu rthermore, it can be postulated that neither cisplatin nor gentamicin induc e a disruption of endothelial cell junction stability in the inner ear.