The role of deferoxamine in the prevention of gentamicin ototoxicity: a histological and audiological study in guinea pigs.
CONCLUSIONS
The addition of deferoxamine to gentamicin seems to confer partial functional and histological protection to the cochlea.


OBJECTIVE
Aminoglycosides are known ototoxic agents. The toxicity occurs via an activation process involving the formation of an iron-gentamicin complex with free radical production. Iron chelation will supposedly limit this toxic effect. This study aimed to determine the possible cochleoprotective role of deferoxamine on the ototoxic effect of gentamicin.


METHODS
Sixty healthy active guinea pigs, weighing 400-600 g, with an average age of 6 months were used. They were divided into three groups. Group 1 received intramuscular gentamicin 8 mg/kg/day, group 2 received gentamicin 8 mg/kg/day and deferoxamine 150 mg/kg twice daily for 19 days and group 3 served as a control. All animals had a baseline measurement of distortion product oto-acoustic emissions. At the end of 33 days they were submitted to another measurement and then the animals were sacrificed and their cochleas were examined histologically by light and transmission electron microscopy.


RESULTS
In group 1 the mean amplitude post-injection ranged from 5.83 dB at 1001 Hz to 22.33 dB at 6348 Hz. In the deferoxamine + gentamicin group the mean amplitude post-injection ranged from 5.10 dB at 1001 Hz, to 24.45 dB at 6348 Hz. This was statistically significant. At 4004, 5042 and 6348 Hz group 2 showed less histological damage than group 1.
Mostafa
Badr Eldin
BE
Department of Otorhinolaryngology, Ain-Shams Faculty of Medicine, Cairo, Egypt. bemostafa@entainshams.com
Tawfik
Somia
S
Hefnawi
Nadia Galal El
NG
Hassan
Mohammed Amir
MA
Ismail
Fouad Abbas
FA
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D003676:Deferoxamine / Q000494:pharmacology*; D005839:Gentamicins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007273:Injections, Intramuscular; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning; D009925:Organ of Corti / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*
D005839:Gentamicins; D007502:Iron Chelating Agents; D003676:Deferoxamine