Gentamicin ototoxicity dissociated from glucose uptake and utilization.
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.
D000818:Animals; D004423:Ear / Q000187:drug effects* / Q000378:metabolism; D005839:Gentamicins / Q000633:toxicity*; D005947:Glucose / Q000378:metabolism*; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives*; D005958:Glucosephosphates / Q000378:metabolism; D006168:Guinea Pigs; D008297:Male
D005839:Gentamicins; D005958:Glucosephosphates; C015785:2-deoxyglucose-6-phosphate; D019298:Glucose-6-Phosphate; D005947:Glucose