Reducing Aminoglycoside Ototoxicity

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Deng, George
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Objective: The objective of this project was to determine whether sodium thiosulphate (STS) could be used clinically to reduce hearing loss caused by gentamicin, an aminoglycoside. First, we established the appropriate dose of gentamicin to induce a mild to moderate sensorineural hearing loss and the most appropriate time to test the hearing loss. Second, we used this model to assess the protective effects of STS and α-tocopherol on gentamicin induced ototoxicity. Methods: C57 male mice (4 – 5 weeks old, 150 – 200g). Phase 1: Thirty mice received gentamicin in increasing doses from 160-220 mg/kg and underwent auditory brainstem response (ABR) testing to assess hearing changes over 3 months. This dose-response relationship was used to optimize Phase2. Phase 2: Six groups of 64 mice were studied. Group1: gentamicin 220 mg/kg i.p. with isotonic (25%) STS 1600 mg/kg. Group2: gentamicin 220 mg/kg i.p. with α-tocopherol 400 mg/kg. Group3: STS 1600 mg/kg i.p. Group4: α-tocopherol 400 mg/kg i.p. Group5: saline i.p. Group 6: gentamicin 220 mg/kg i.p. ABRs were recorded at baseline and at 30 days. Results: Phase 1: The optimal mouse model for this type of research should employ a dose of 220 mg/kg and study animals at one month. Phase 2: Threshold changes for the treatment group that received STS with gentamicin were not statistically significantly different from gentamicin without STS. Gentamicin induced threshold shifts of about 15 dB at one month and great variability was found in the response. Conclusion: STS does not offer protection against gentamicin induced hearing loss.