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 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.
Department of Otolaryngology, University of Tübingen, Germany.
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Zenner
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Keiner
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Zimmermann
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism; D016257:Fura-2; D005839:Gentamicins / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000633:toxicity; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology*; D019803:Glutathione Disulfide; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D011188:Potassium / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D013997:Time Factors
D015220:Calcium Channels; D005839:Gentamicins; D013438:Sulfhydryl Compounds; D005978:Glutathione; D011188:Potassium; D002118:Calcium; D016257:Fura-2; D019803:Glutathione Disulfide