SPECIFIC GLUTATHIONE-SH INHIBITION OF TOXIC EFFECTS OF METABOLIZED GENTAMICIN ON ISOLATED GUINEA-PIG HAIR-CELLS

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 unstimulate d OHC and inhibit increases in intracellular Ca2+ concentrations durin g K+-induced depolarization. Glutathione-SH (GSH), a detoxificating ag ent, did not interfere with G and mG effects on intracellular Ca2+ con centration. In non-stimulated OHC, mG but not G induced pathological O HC 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 probabl y inhibits mG-induced pathological opening of transduction channels. T hese results suggest that GSH selectively inhibits mG-specific toxic e ffects on the guinea pig OHC, possibly by enzymatic detoxification.