Self-protection against aminoglycoside ototoxicity in guinea pigs.
BACKGROUND
Amikacin is a semisynthetic aminoglycoside. It acts against most of the microbial species. Amikacin limitation of the therapeutic application is the ototoxicity which promotes permanent lesions in the cochlear system. Aminoglycoside antibiotics have ototoxic potential. The target cells are preferentially the outer hair cells in the cochlear basal turns. Amynoglicoside antibiotics can quelate iron forming a complex with oxidate properties and promotes the formation of free radicals. Responsible for production of lesions in the hair cells.


OBJECTIVE
The objective of the present investigation was to determine whether the use of the aminoglycoside amikacin at small doses may lead to the occurrence of some types of resistance to or protection against ototoxicity of the drug by analyzing lesions to the organ of Corti by scanning electron microscopy.


METHODS
The study was conducted on 31 guinea pigs that were divided into 4 groups, amikacin was administered intramuscularly. The groups consisted of: group A = control group: 5 animals (10 cochleae); group B = 5 animals (10 cochleae), amikacin 20 mg/kg/day for 30 days; group C = 7 animals (13 cochleae), amikacin 400 mg/kg/day for 12 days; group d = 14 animals (26 cochleae) amikacin 20 mg/kg/day for 30 days, followed by 400 mg/kg/day for 12 days. Histological studies were performed by scanning electron microscopy. Three cochleae were excluded.


RESULTS
In groups A and B, the cells were normal in all cochleae, in group C there were extensive lesions of the 2 more basal turns, and in group D there was a significant reduction of lesions in the 2 more basal turns compared with group C, which had received the ototoxic dose of amikacin alone.


CONCLUSIONS
We conclude that the non-ototoxic dose of amikacin administered before the ototoxic dose of the same antibiotic had a statistically significant protective effect on the 2 more basal turns of the guinea pig cochlea.
Oliveira
J A A de
JA
Servicio de Otorhinolaryngology, University Hospital, Faculty of Medicine of Ribeirão Preto, São Paulo, Brazil.
Canedo
D M
DM
Rossato
M
M
Andrade
M H de
MH
D000583:Amikacin / Q000008:administration & dosage* / Q000633:toxicity*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000633:toxicity*; D004351:Drug Resistance; D004427:Ear Diseases / Q000139:chemically induced*; D006168:Guinea Pigs; D008297:Male; D008855:Microscopy, Electron, Scanning; D009925:Organ of Corti / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure
D000900:Anti-Bacterial Agents; D000583:Amikacin