Blood-perilymph barrier and ototoxicity: an in vivo study in the rat.
Cisplatin and gentamicin are two ototoxicants that are supposed to be transported by the paracellar route, i.e. via cellular junctions, to the perilymphatic compartment. This study was initiated to test the hypothesis that susceptive variation of individuals to ototoxic drugs may be explained by variability in transport properties. The transport of radioactive mannitol through the blood-perilymph barrier was correlated in vivo with the acute effect of cisplatin and gentamicin on auditory function. Transport of radioactive 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 not correlate with the ototoxic effect of cisplatin, evaluated as changes in the auditory-evoked brainstem response thresholds or loss of outer hair cells. The results provide evidence that the barrier function is not involved in the interindividual variability of the ototoxic effect of cisplatin. Furthermore, it can be postulated that neither cisplatin nor gentamicin induce a disruption of endothelial cell junction stability in the inner ear.
Laurell
G
G
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden. goran.laurell@ks.se
Viberg
A
A
Teixeira
M
M
Sterkers
O
O
Ferrary
E
E
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D001769:Blood; D002199:Capillary Permeability; D002945:Cisplatin / Q000009:adverse effects / Q000493:pharmacokinetics*; D004427:Ear Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000503:physiopathology; D004594:Electrophysiology; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D005839:Gentamicins / Q000009:adverse effects / Q000493:pharmacokinetics*; D006198:Hair Cells, Auditory / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008353:Mannitol; D010498:Perilymph; D011877:Radionuclide Imaging; D051381:Rats; D020318:Rats, Long-Evans
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D005839:Gentamicins; D008353:Mannitol; D002945:Cisplatin