[Glutathione-SH as protection from cytotoxic side-effects of gentamycin. Studies with isolated outer hair cells].
Hearing loss with irreversible cochlear damage can be the consequence of aminoglycoside treatment. The present investigation found that metabolized gentamicin (mG) but not native gentamicin (G) was cytotoxic for isolated guinea pig outer hair cells (OHC). Glutathione-SH (GSH), a detoxifying agent, completely inhibited the cytotoxic effects of mG. Using FURA-2 fluorescence, both G and mG were found to reduce intracellular Ca2+ concentrations in unstimulated OHC and inhibit increases in Ca2+ concentrations during K(+)-induced depolarization. GSH did not interfere with G and mG effects on intracellular Ca2+ concentrations. In unstimulated OHC, mG but not G induced pathological OHC depolarization, indicating opening of transduction channels to allow influx of K+ ions. GSH inhibited this effect, suggesting that GSH probably inhibits mG-induced pathological opening of transduction channels. In so doing GSH may inhibit ototoxic side-effects of mG.
Keiner
S
S
Universitäts-HNO-Klinik Tübingen.
Zimmermann
U
U
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D000931:Antidotes / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D005839:Gentamicins / Q000493:pharmacokinetics / Q000633:toxicity*; D005978:Glutathione / Q000494:pharmacology*; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000473:pathology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013439:Sulfhydryl Reagents / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000931:Antidotes; D005839:Gentamicins; D013439:Sulfhydryl Reagents; D005978:Glutathione; D011188:Potassium; D002118:Calcium