Attenuation of aminoglycoside ototoxicity by glutathione.
Aminoglycoside antibiotics are commonly used for the treatment of serious gram-negative infections despite a high incidence of associated ototoxicity. Attempts to elucidate the mechanisms of toxicity or prevent the adverse effects have previously been unsuccessful. Recently, the damaging effects of aminoglycosides on the inner ear have been shown to be caused by a metabolite of the drug, implying an enzymatic conversion of the parent compound. Glutathione has been suggested to be closely related to the detoxification mechanisms of this metabolite. This study revealed the possible attenuation of aminoglycoside ototoxicity by glutathione. Guinea pigs were given amikacin alone or amikacin with prior intramuscular injection of glutathione. The pretreatment of glutathione significantly reduced the damage of outer hair cells of the organ of Corti. This may indicate that glutathione reduces the aminoglycoside ototoxicity and can be favorably applied in clinical use.
Nishida
I
I
Department of Otolaryngology, WFAC Hiroshima General Hospital, Japan.
Takumida
M
M
D000583:Amikacin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005978:Glutathione / Q000494:pharmacology*; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects*; D007273:Injections, Intramuscular; D009410:Nerve Degeneration / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000583:Amikacin; D005978:Glutathione