Ototoxicity and otoprotection in the inner ear of guinea pigs using gentamicin and amikacin: ultrastructural and functional aspects.
Ototoxicity is still a challenge to medicine. The discovery of self-protecting endogenous mechanisms of the outer hair cells associated with their functional and ultra-structural assessment methods has opened new horizons in the understanding and controlling of these mechanisms.


OBJECTIVE
this paper aimed at establishing whether or not underdoses of gentamicin could protect the inner ear against the harmful effects of amikacin, based on these protection mechanisms and determine if the otoacoustic emission amplitudes could be associated with the level of hair cell integrity.


METHODS
Experimental study. We used 31 guinea pigs. They were injected with saline solution, gentamicin and amikacin, alone and in combinations -intramuscular injections - during 12, 30 and 42 days. The otoacoustic emissions were recorded in the beginning and at the end of the experiment, comparing it with the cochlear integrity study carried out by electron microscopy.


RESULTS
gentamicin underdoses did not protect the inner ear against amikacin toxicity; the reduction in otoacoustic emissions was strongly associated with an increase in hair cell lesions.


CONCLUSIONS
these findings help understand inner ear otoprotection and ototoxicity. Establishing the correlation between the emissions amplitude an cell integrity plays an important role in the follow up of hair cell damage, with possible monitoring of ototoxicity caused by drugs in humans.
de Aquino
Thomaz José Marra
TJM
PhD at USP / FMRP, Department of Ophthalmology, Otorhinolaryngology, Head and Neck Surgery at Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. Electronic address: tjaquino@usp.br.
de Oliveira
José Antônio Apparecido
JAA
Associate Professor at Universidade de São Paulo, Full Professor in the Department of Ophthalmology, Otorhinolaryngology, Head and Neck Surgery at Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo.
Rossato
Maria
M
Audiology Technician, Department of Ophthalmology, Otorhinolaryngology, Head and Neck Surgery at Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo.; Department of Ophthalmology, Otorhinolaryngology, Head and Neck Surgery at Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo.
D000583:Amikacin / Q000009:adverse effects*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D007758:Ear, Inner / Q000187:drug effects* / Q000648:ultrastructure; D005839:Gentamicins / Q000008:administration & dosage / Q000627:therapeutic use*; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008855:Microscopy, Electron, Scanning; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D000583:Amikacin