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 in...

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Bibliographic Details
Published in:European archives of oto-rhino-laryngology 1994-04, Vol.251 (2), p.84-90
Main Authors: ZENNER, H. P, KEINER, S, ZIMMERMANN, U
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Calcium - metabolism
Calcium Channels - drug effects
Cell Survival - drug effects
Cytoplasm - metabolism
Drug toxicity and drugs side effects treatment
Fura-2
Gentamicins - antagonists & inhibitors
Gentamicins - metabolism
Gentamicins - toxicity
Glutathione - analogs & derivatives
Glutathione - pharmacology
Glutathione Disulfide
Guinea Pigs
Hair Cells, Auditory, Outer - cytology
Hair Cells, Auditory, Outer - drug effects
Hair Cells, Auditory, Outer - metabolism
Medical sciences
Membrane Potentials - drug effects
Microelectrodes
Pharmacology. Drug treatments
Potassium - pharmacology
Signal Transduction - drug effects
Sulfhydryl Compounds - pharmacology
Time Factors
Toxicity: respiratory system, ent, stomatology
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Summary: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.
ISSN:0937-4477
1434-4726
DOI:10.1007/BF00179898