title: Combined administration of kanamycin and furosemide does not result in loss of vestibular function in Guinea pigs.
abstract: Aminoglycoside antibiotics are known to damage the vestibular and auditory sensory epithelia. Although loop diuretics enhance the cochleotoxic effect of aminoglycosides, it is not known whether concomitant administration of an aminoglycoside and a loop diuretic affects the vestibular system. The aim of our study was to investigate the effect of co-administration of kanamycin and furosemide upon the otolith organs and to compare it to the known vestibulotoxic effect of gentamicin. Five guinea pigs were injected with a single dose of both kanamycin (400 mg/kg, s.c.) and furosemide (100 mg/kg, i.v.), 5 animals received gentamicin (100 mg/kg, i.p.) for 10 days, and 5 untreated animals served as controls. After 7 days, vestibular function was assessed by measuring vestibular short-latency evoked potentials (VsEPs) to linear acceleration stimuli and cochlear function by auditory brainstem responses (ABRs) to clicks. Hair cell densities were determined in phalloidin-stained whole mounts of the utricles and saccules, and in midmodiolar sections of resin-embedded cochleae. Co-administration of kanamycin and furosemide had no significant effect on VsEPs and hair cell densities in the utricles and saccules were not reduced. ABR thresholds were increased to a great extent (by ∼60 dB), and histologically a severe loss of cochlear hair cells was observed. The effect of gentamicin, both on vestibular and cochlear function, was just the opposite. VsEP thresholds to horizontal stimulation were elevated and suprathreshold amplitudes showed a decrease, whereas cochlear function was not reduced. With this protocol, we have a tool to selectively induce cochlear or vestibular damage, which may be of interest to researchers and clinicians alike.
authors.affiliation: Department of Otorhinolaryngology and Head and Neck Surgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Bremer
authors.forename: John C M J
authors.initials: JC
authors.lastname: de Groot
authors.forename: Huib
authors.initials: H
authors.lastname: Versnel
authors.forename: Sjaak F L
authors.initials: SF
authors.lastname: Klis
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D003051:Cochlea / Q000187:drug effects; D004232:Diuretics / Q000008:administration & dosage*; D005260:Female; D005665:Furosemide / Q000008:administration & dosage*; D005839:Gentamicins / Q000008:administration & dosage; D006168:Guinea Pigs; D018069:Hair Cells, Vestibular / Q000187:drug effects*; D007612:Kanamycin / Q000008:administration & dosage*; D010037:Otolithic Membrane / Q000187:drug effects*; D058585:Vestibular Evoked Myogenic Potentials / Q000187:drug effects; D014724:Vestibular Function Tests
chemical_list: D000900:Anti-Bacterial Agents; D004232:Diuretics; D005839:Gentamicins; D007612:Kanamycin; D005665:Furosemide