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Are aminoglycoside antibiotics excitotoxic?
1Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor 48109-0506, USA.
Neuroreport
|January 6, 1999
Summary
Gentamicin causes hearing loss, but maleic acid, tartaric acid, and DMSO offer protection. This suggests antioxidants may prevent aminoglycoside-induced ototoxicity.
Area of Science:
- Ototoxicity research
- Pharmacology
- Neuroscience
Background:
- Aminoglycosides, like gentamicin, are known to cause ototoxicity, leading to hearing loss.
- The exact mechanism of gentamicin-induced hearing damage is still under investigation, with free-radical involvement being a leading hypothesis.
Purpose of the Study:
- To investigate the protective effects of maleic acid, tartaric acid, and dimethyl sulfoxide (DMSO) against gentamicin-induced hearing loss in guinea pigs.
- To explore the potential role of free radicals in aminoglycoside ototoxicity.
Main Methods:
- Guinea pigs were administered gentamicin to induce hearing loss.
- Concomitant administration of maleic acid or tartaric acid dissolved in DMSO was given to assess protective effects.
- Auditory threshold shifts were measured to quantify hearing loss.
Main Results:
- Gentamicin induced a significant hearing loss of 61 dB at 18 kHz.
- Co-administration of maleic acid or tartaric acid in DMSO reduced the hearing threshold shift to below 40 dB.
- The protective compounds act as metal chelators and free-radical scavengers.
Conclusions:
- The findings support a free-radical mechanism in gentamicin ototoxicity.
- Caution is advised regarding the use of maleic acid, tartaric acid, and DMSO as vehicles in ototoxicity studies.
- Simple antioxidants may serve as an effective and economical prophylaxis against aminoglycoside-induced hearing loss.