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Gentamicin ototoxicity dissociated from glucose uptake and utilization
Abstract:
The hypothesis was tested that gentamicin causes loss of cochlear microphonic potentials by interfering with glucose transport or metabolism in cochlear structures. Gentamicin (3 or 10 mM), applied by perilymphatic perfusion in the guinea pig, reduced cochlear microphonics in a dose-dependent manner. The presence of 5 mM glucose lowered the initial rate but not the final (60 min) loss of cochlear microphonics. Glucosamine (2-deoxy-2-aminoglucose), a reported inhibitor of glucose transport, had no effect at concentrations as high as 20 mM. Glucose utilization was measured by introducing radiolabeled deoxyglucose into the perfusate and determining its uptake into inner ear tissues. Concentrations of deoxyglucose-6-phosphate in organ of Corti and in stria vascularis increased linearly with time and remained unaffected by the presence of 3 mM gentamicin. Ten mM gentamicin reduced deoxyglucose uptake by 30% in the lateral wall tissues but not in the organ of Corti preparation. The lack of correlation between loss of microphonics and glucose utilization does not support interference with glucose metabolism as a primary mechanism of aminoglycoside ototoxicity.
Insights
Gentamicin (an antibiotic) can harm hearing by affecting cochlear microphonics. However, this study found gentamicin does not primarily harm hearing by interfering with glucose transport or metabolism in the inner ear.
Area of Science:
- Ototoxicity
- Neuroscience
- Pharmacology
Background:
- Aminoglycoside antibiotics, like gentamicin, are known to cause ototoxicity.
- The precise mechanisms underlying gentamicin-induced ototoxicity remain under investigation.
- Glucose metabolism is crucial for cochlear function.
Purpose of the Study:
- To investigate whether gentamicin-induced loss of cochlear microphonic potentials is mediated by interference with glucose transport or metabolism.
- To explore the relationship between gentamicin concentration and its effects on cochlear function and glucose utilization.
Main Methods:
- Guinea pig model with perilymphatic perfusion of gentamicin.
- Measurement of cochlear microphonic potentials.
- Assessment of glucose utilization using radiolabeled deoxyglucose uptake in cochlear tissues.
- Evaluation of glucosamine's effect on cochlear function.
Main Results:
- Gentamicin reduced cochlear microphonics in a dose-dependent manner.
- The presence of glucose did not prevent the final loss of cochlear microphonics.
- Glucosamine did not inhibit cochlear microphonic loss.
- Gentamicin did not affect deoxyglucose uptake in the organ of Corti but reduced it in lateral wall tissues.
Conclusions:
- The findings do not support interference with glucose metabolism as the primary mechanism of gentamicin ototoxicity.
- Gentamicin's ototoxic effects are not directly correlated with impaired glucose utilization in the organ of Corti.
- Further research is needed to elucidate the exact mechanisms of aminoglycoside-induced hearing loss.