Ototoxicity in vitro: effects of neomycin, gentamicin, dihydrostreptomycin, amikacin, spectinomycin, neamine, spermine and poly-L-lysine.
The effects that the aminoglycoside-aminocyclitol antibiotics amikacin, dihydrostreptomycin, gentamicin, neomycin, and spectinomycin, the neomycin fragment neamine, and the polybasic compounds spermine and poly-L-lysine, have on outer hair cells in cochlear cultures prepared from the early post-natal mouse have been assessed using both scanning and transmission electron microscopy (SEM and TEM). The antibiotics were used at concentrations ranging from 0.25-1.0 mM, spermine from 10 microM to 3.0 mM, and poly-L-lysine from 0.05-2 microM. Qualitative assessment of apical surface damage allows the antibiotics to be ranked in the following order: neomycin > gentamicin > dihydrostreptomycin > amikacin > neamine > spectinomycin. At a concentration of 1 mM spectinomycin is essentially non-toxic and the effects of neamine are marginal. Poly-L-lysine and spermine also cause surface damage, with poly-L-lysine being substantially more toxic than any of the antibiotics, and spermine ranking, on the basis of SEM observations, between dihydrostreptomycin and amikacin. TEM indicates that although all toxic compounds cause damage to the apical surface of the hair cell, only neomycin, poly-L-lysine and spermine induce the formation of whorls of tightly packed membrane resembling myelin within the apical surface lesions to any great extent. Apical-surface changes induced by dihydrostreptomycin and amikacin are simply large distensions of the cell filled with cytoplasmic organelles of normal appearance. Although the effects of the aminoglycoside antibiotics are largely limited to the apical surface of the cell, poly-L-lysine induces complete necrosis of the cell, and spermine causes a dramatic increase in cytoplasmic electron density and condensation of the nuclear chromatin.
Kotecha
B
B
School of Biological Sciences, University of Sussex, Falmer, Brighton, UK.
Richardson
G P
GP
D000583:Amikacin / Q000633:toxicity; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D046508:Culture Techniques; D003593:Cytoplasm / Q000648:ultrastructure; D004096:Dihydrostreptomycin Sulfate / Q000633:toxicity; D005839:Gentamicins / Q000633:toxicity; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000648:ultrastructure; D051379:Mice; D017348:Microscopy, Electron, Scanning Transmission; D009355:Neomycin / Q000633:toxicity; D009925:Organ of Corti / Q000187:drug effects* / Q000648:ultrastructure; D011107:Polylysine / Q000633:toxicity; D000198:Spectinomycin / Q000633:toxicity; D013096:Spermine / Q000633:toxicity; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D011107:Polylysine; D013096:Spermine; D000583:Amikacin; D000198:Spectinomycin; D009355:Neomycin; D004096:Dihydrostreptomycin Sulfate