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Structural changes in the human stria vascularis induced by aminoglycosides and loop diuretics
Anthony Wright1, Andrew Forge1, Daniel J Jagger1
1UCL Ear Institute, University College London, 332 Gray's Inn Road, London, WC1X 8EE, United Kingdom.
Loop diuretics and aminoglycoside antibiotics cause ultrastructural changes in the human stria vascularis, similar to those seen in animal models. This supports using animals to predict drug-induced ototoxicity in humans.
Area of Science:
- Ototolaryngology
- Pharmacology
- Cell Biology
Background:
- The stria vascularis is crucial for maintaining the cochlear environment.
- Drug-induced ototoxicity is a significant clinical concern, particularly with loop diuretics and aminoglycosides.
- Understanding the human stria vascularis' response to these drugs is vital for predicting and preventing hearing loss.
Purpose of the Study:
- To examine the ultrastructural effects of loop diuretics and aminoglycoside antibiotics on the human stria vascularis.
- To compare human tissue changes with those observed in animal models of ototoxicity.
- To validate the use of animal models for predicting human ototoxicity.
Main Methods:
- Human stria vascularis tissues from normal controls and patients treated with loop diuretics, aminoglycosides, or both were analyzed.
- Scanning and transmission electron microscopy were employed.
- Tissues were preserved via perilymphatic perfusion fixation within one hour of death.
Main Results:
- Normal human stria vascularis ultrastructure is similar to that of experimental animals.
- Loop diuretics induced changes indistinguishable from those in animal models.
- Aminoglycosides caused alterations, potentially influenced by concurrent renal failure.
- Combined treatment showed a spectrum of mild to severe ultrastructural changes.
Conclusions:
- Loop diuretics and aminoglycosides induce characteristic ultrastructural changes in the human stria vascularis.
- Observed human changes closely resemble those in animal models, supporting their predictive value.
- These findings reinforce the utility of animal models in assessing drug-induced ototoxicity for human health.
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