Uptake of amikacin by hair cells of the guinea pig cochlea and vestibule and ototoxicity: comparison with gentamicin.
The distribution of amikacin (AK), an exclusive cochleo-toxic aminoglycosidic antibiotic (AA), and of gentamicin (GM), which is both cochleo- and vestibulo-toxic, has been studied in cochlear and vestibular hair cells. Guinea pigs were treated during six days with one daily injection of AK (450 mg/kg/day) or GM (60 mg/kg/day). AAs were detected, using immunocytochemical technique with scanning laser confocal microscopy, in isolated cells from guinea pigs sacrificed from 2 to 30 days after the end of the treatments. Results demonstrate a rapid uptake (as soon as after 2-day treatment) of both AAs by cochlear and vestibular hair cells and a very slow clearance. Particularly GM and AK are detected in type I and type II hair cells of the utricles and cristae ampullaris. The presence of these two molecules with different toxic potentialities towards cochlear and vestibular hair cells indicates that the selective ototoxicity of aminoglycosides cannot be explained simply on the basis of particular uptake and accumulation in the different sensory hair cells.
Aran
J M
JM
Laboratoire d'Audiologie Expérimentale, Inserm U 229, Hôpital Pellegrin, Bordeaux, France.
Chappert
C
C
Dulon
D
D
Erre
J P
JP
Aurousseau
C
C
D000583:Amikacin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D003051:Cochlea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018069:Hair Cells, Vestibular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D012444:Saccule and Utricle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D005839:Gentamicins; D000583:Amikacin