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Are aminoglycoside antibiotics excitotoxic?
1Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor 48109-0506, USA.
Abstract:
Guinea pigs received gentamicin to induce a profound hearing loss (61 dB auditory threshold shift at 18 kHz). Concomitant administration of maleic or tartaric acid dissolved in dimethyl sulfoxide (DMSO) significantly reduced the threshold shift to < 40 dB. The results have several important implications. First, they support the hypothesis of a free-radical mechanism of gentamicin toxicity since the protective compounds are metal chelators and scavengers. Second, they caution against these and similar chemicals, commonly found in drug preparations, as vehicles in tests of aminoglycoside toxicity. For example, a recent study by others describing attenuation of aminoglycoside ototoxicity by NMDA antagonists may have been influenced by the presence of maleate, tartrate and DMSO. Third, they suggest simple antioxidants as a potentially efficient and inexpensive clinical prophylaxis of aminoglycoside-induced hearing loss.
Insights
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.