Prevention of aminoglycoside-induced sensorineural hearing loss.
BACKGROUND
Aminoglycoside antibiotics are some of the most commonly used agents for treating gram-negative bacterial infections. They are extremely efficacious but can result in ototoxicity. It has been postulated that the mechanism inducing damage is the formation of oxygen free radicals. Many compounds have been employed in an attempt to reduce aminoglycoside-induced hearing loss. We endeavour to do likewise using sodium thiosulphate. This free radical scavenging agent has a proven ability to minimize cochlear damage owing to the chemotherapeutic agent cisplatin.


OBJECTIVE
This study had two distinct objectives. The first was to determine if sodium thiosulphate can reduce hearing loss in C57 mice concurrently subjected to gentamicin. The second goal was to assess the value of this animal model.


METHODS
This study was accomplished by creating four treatment arms. The animals were provided with daily intraperitoneal injections of gentamicin (120 mg/kg), sodium thiosulphate (1600 mg/kg), gentamicin plus sodium thiosulphate, or normal saline. Auditory brainstem response threshold changes were calculated comparing differences between baseline values and those observed at day 35.


RESULTS
The results indicate a trend suggesting that sodium thiosulphate may afford some degree of otologic protection when provided in conjunction with gentamicin. However, a statistical significance could not be established. Our mice appear to be more resistant to gentamicin-induced ototoxicity than found in previously reported animal models.


CONCLUSIONS
We were unable to demonstrate that sodium thiosulphate can attenuate gentamicin-induced ototoxicity. Furthermore, we observe that the susceptibility to hearing loss varies considerably between individual C57 mice. Consequently, we hold some degree of reservation with the use of this model to assess the benefit of prospective rescue agents.
Hochman
Jordan
J
Department of Otolaryngology, University of Manitoba, Winnipeg, Manitoba.
Blakley
Brian W
BW
Wellman
Mark
M
Blakley
Laura
L
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D000975:Antioxidants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004351:Drug Resistance; D016057:Evoked Potentials, Auditory, Brain Stem; D005839:Gentamicins / Q000009:adverse effects*; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D013885:Thiosulfates / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D000975:Antioxidants; D005839:Gentamicins; D013885:Thiosulfates; C017717:sodium thiosulfate