ATTENUATION OF NEOMYCIN OTOTOXICITY BY IRON CHELATION

Increasing evidence suggests that aminoglycoside ototoxicity is mediat ed by the formation of an aminoglycoside-iron complex and that the cre ation of this complex is a preliminary step in generation of free radi cal species and subsequent hair cell death. In this study we have asse ssed the ability of the iron chelator deferoxamine to attenuate the he aring loss induced by an ototoxic dose of the aminoglycoside neomycin (100 mg/kg per day for 14 days). Experiments were carried out on pigme nted guinea pigs weighing 250 to 300 g. Changes in auditory sensitivit y were characterized by monitoring shifts in compound action potential (CAP) thresholds, recorded through indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. Results show tha t animals receiving neomycin alone suffered a mean threshold shift exc eeding 35 dB at all test frequencies (2.0, 4.0, and 8.0 kHz) 30 days a fter initiation of treatment, In comparison, all animals receiving cot herapy of neomycin and deferoxamine (150 mg/kg twice daily for 14 days ) maintained their CAP threshold, suggesting significant protection fr om neomycin ototoxicity. A statistical comparison of treatment groups showed that in the animals receiving cotherapy with neomycin and defer oxamine, deferoxamine produced a significant protective effect against neomycin-induced ototoxicity (P < 0.001). These results provide furth er evidence of the intrinsic role of iron in aminoglycoside ototoxicit y and suggest that deferoxamine may have a therapeutic role in attenua ting the cytotoxic action of aminoglycoside antibiotics.