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Effects of perilymphatically perfused gentamicin on microphonic potential, lipid labeling and morphology of cochlear
Abstract:
The perilymphatic space of the guinea pig was perfused in situ with artificial perilymph containing [32P] orthophosphate and 3H-glycerol while cochlear microphonic potentials (CM) were monitored. The perfusion of 10 mM gentamicin suppressed CM by 62% within 30 min. 32P-incorporation into phosphatidylinositol bisphosphate in the organ of Corti was decreased but distribution of 3H-glycerol in neutral lipids and phospholipids was not affected by gentamicin. The morphological evaluation included all structures lining the scala media, the spiral ligament, the basal membrane and the vestibular organs. Hair cells sometimes contained small intracellular 'precipitation' lines but, in general, ultrastructure of all tissues was essentially normal and no overt histopathological changes were evident. The observed biochemical changes should, therefore, represent early and primary actions of the drug. This confirms the hypothesis that an interaction with the acidic phospholipid, phosphatidylinositol bisphosphate, is an important step in the ototoxic mechanism of amino-glycoside antibiotics.
Insights
Gentamicin, an antibiotic, disrupts inner ear function by affecting phosphatidylinositol bisphosphate in the organ of Corti. This biochemical change, observed in guinea pigs, is a key step in aminoglycoside-induced ototoxicity.
Area of Science:
- Ototoxicity research
- Biochemistry of hearing
- Pharmacology of antibiotics
Background:
- Aminoglycoside antibiotics are widely used but can cause ototoxicity.
- The precise molecular mechanisms underlying aminoglycoside ototoxicity remain incompletely understood.
- Previous hypotheses suggested interactions with cellular lipids.
Purpose of the Study:
- To investigate the early biochemical effects of gentamicin on the cochlea.
- To examine the impact of gentamicin on lipid metabolism in the organ of Corti.
- To test the hypothesis that phosphatidylinositol bisphosphate is involved in gentamicin ototoxicity.
Main Methods:
- In situ perfusion of guinea pig perilymphatic space with radiolabeled compounds ([32P] orthophosphate, 3H-glycerol).
- Monitoring of cochlear microphonic potentials (CM) during perfusion.
- Biochemical analysis of lipid incorporation and morphological evaluation of cochlear tissues.
Main Results:
- Gentamicin perfusion significantly suppressed CM by 62%.
- 32P incorporation into phosphatidylinositol bisphosphate decreased, while 3H-glycerol distribution remained unaffected.
- No significant ultrastructural histopathological changes were observed in cochlear tissues.
Conclusions:
- Biochemical changes, specifically decreased 32P incorporation into phosphatidylinositol bisphosphate, represent early actions of gentamicin.
- These findings support the hypothesis that interaction with phosphatidylinositol bisphosphate is a crucial step in aminoglycoside-induced ototoxicity.