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Effects of neomycin on polyphosphoinositides in inner ear tissues and monomolecular films
Abstract:
The effect of neomycin on polyphosphoinositides was studied in vivo and in vitro. In vivo, the incorporation of 32Pi into phosphatidylinositol phosphate and phosphatidylinositol diphosphate was measured in inner ear tissues. Concentrations of neomycin which decreased the electrophysiological response of the chochlea to sound stimulation also decreased labeling of phosphatidylinositol diphosphate. In vitro experiments with brain tissues and polyphosphoinositide extracts indicated a direct interaction between the lipids and neomycin. Neomycin interacts strongly with monomolecular films of polyphosphoinositides. The interaction appears to be complex and is a function of neomycin concentration in the subphase and surface pressure of the film. Condensation of the polyphosphoinositide film is favored at low neomycin concentrations and low film pressures while expansion of the film is favored at high neomycin concentrations and high film pressures. The interactions of neomycin with other negatively charged films (phosphatidyl inositol and phosphatidyl serine) are much weaker, particularly at low neomycin concentrations. The metabolic and physiological consequences of the neomycin/polyphosphoinositide interaction are discussed in regard to the ototoxicity of the drug.
Insights
Neomycin disrupts inner ear polyphosphoinositides, affecting hearing function. This drug-lipid interaction, studied in vivo and in vitro, may explain neomycin's ototoxicity.
Area of Science:
- Biochemistry
- Neuroscience
- Pharmacology
Background:
- Neomycin is an antibiotic known for ototoxicity.
- Polyphosphoinositides are crucial membrane lipids involved in cellular signaling.
Purpose of the Study:
- To investigate the interaction between neomycin and polyphosphoinositides.
- To elucidate the role of this interaction in neomycin-induced ototoxicity.
Main Methods:
- In vivo studies measured 32P incorporation into phospholipids in inner ear tissues.
- In vitro experiments analyzed neomycin's interaction with polyphosphoinositide films and extracts.
- Electrophysiological responses of the cochlea were assessed.
Main Results:
- Neomycin decreased phosphatidylinositol diphosphate labeling in inner ear tissues, correlating with reduced cochlear response.
- In vitro, neomycin interacted strongly with polyphosphoinositides in a concentration-dependent manner.
- Neomycin's interaction with other negatively charged lipids was significantly weaker.
Conclusions:
- Neomycin directly interacts with polyphosphoinositides, altering their properties.
- This interaction is a potential mechanism underlying neomycin's ototoxic effects.
- Understanding this interaction may inform strategies to mitigate drug-induced hearing loss.