Abstract
The present investigation has shown that only metabolized gentamicin (mG) but not native gentamicin (G) is cytotoxic for isolated guinea pig outer hair cells (OHC). Using FURA-2 fluorescence, both G and mG were found to reduce intracellular free Ca2+ concentrations in unstimulated OHC and inhibit increases in intracellular Ca2+ concentrations during K+-induced depolarization. Glutathione-SH (GSH), a detoxificating agent, did not interfere with G and mG effects on intracellular Ca2+ concentration. In non-stimulated OHC, mG but not G induced pathological OHC depolarization, indicating the opening of transduction channels to allow influx of K+ ions. GSH completely inhibited the lytic effect of mG. Electrophysiological investigations also revealed that GSH probably inhibits mG-induced pathological opening of transduction channels. These results suggest that GSH selectively inhibits mG-specific toxic effects on the guinea pig OHC, possibly by enzymatic detoxification.
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Zenner, H.P., Keiner, S. & Zimmermann, U. Specific glutathione-SH inhibition of toxic effects of metabolized gentamicin on isolated guinea pig hair cells. Eur Arch Otorhinolaryngol 251, 84–90 (1994). https://doi.org/10.1007/BF00179898
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DOI: https://doi.org/10.1007/BF00179898