An energy-dependent step in aminoglycoside ototoxicity: prevention of gentamicin ototoxicity during reduced endolymphatic potential.
Guinea pigs received a bolus of gentamicin (10 mM for 5 min) by perilymphatic perfusion which normally led to an irreversible loss of the cochlear microphonic potential (CM). Various experimental conditions that reduced the endolymphatic potential (EP) were then superimposed on the gentamicin application. Reversible reductions in EP (and, concomitantly, in CM) were induced by asphyxia (3 min), intravenous furosemide (50 mg/kg), and perilymphatic perfusion of aminooxyacetic acid (10 mM). When the administration of gentamicin was initiated at the time of maximal EP reduction the usual irreversible gentamicin-induced decline of CM was prevented. The results indicate that a metabolic process is essential in the expression of gentamicin toxicity. The data are consistent with the inhibition of an energy-dependent transport of the aminoglycoside. Alternatively, the data are also compatible with the hypothesis that entry of gentamicin into hair cells is prevented by a reduction in their transmembrane electrical potential.
D000617:Aminoglycosides / Q000009:adverse effects*; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D003055:Cochlear Microphonic Potentials / Q000187:drug effects*; D004427:Ear Diseases / Q000139:chemically induced* / Q000517:prevention & control; D004710:Endolymph / Q000502:physiology*; D004734:Energy Metabolism; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D005665:Furosemide / Q000494:pharmacology; D005839:Gentamicins / Q000009:adverse effects*; D006168:Guinea Pigs; D000860:Hypoxia / Q000503:physiopathology; D007275:Injections, Intravenous; D007761:Labyrinthine Fluids / Q000502:physiology*; D008297:Male; D009994:Osmolar Concentration
D000617:Aminoglycosides; D005839:Gentamicins; D000625:Aminooxyacetic Acid; D005665:Furosemide