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Effects of ototoxic diuretics (loop diuretics) on the endolymphatic sac
C Erwall1, U Friberg, D Bagger-Sjöbäck
1Department of Otolaryngology, University Hospital, Uppsala, Sweden.
Summary
Loop diuretics like ethacrynic acid and furosemide cause immediate changes in the endolymphatic sac, suggesting secretory activity. Chronic exposure alters cell structure, likely secondary to inner ear fluid imbalances.
Area of Science:
- Ototolaryngology
- Cell Biology
- Pharmacology
Background:
- Loop diuretics, ethacrynic acid (EA) and furosemide (FU), are known to affect inner ear structures.
- These diuretics can induce morphological alterations in the stria vascularis and reduce endocochlear potential.
Purpose of the Study:
- To investigate the acute and chronic structural effects of ethacrynic acid and furosemide on the murine endolymphatic sac.
- To determine if observed changes are a direct toxic effect or secondary to altered inner ear homeostasis.
Main Methods:
- Light and transmission electron microscopy were used to examine endolymphatic sac structure.
- Mice were treated with single intravenous injections or daily intraperitoneal injections of EA or FU.
Main Results:
- Acute EA/FU treatment caused immediate changes in light cells, including increased endoplasmic reticulum, prominent Golgi, and granule formation, suggesting secretory activity.
- Chronic subtoxic EA/FU doses led to altered epithelial cytoarchitecture, with light cells being obscured by dark cells.
- A precipitate on the luminal cell membrane suggested secretory activity.
Conclusions:
- Acute and chronic treatment with loop diuretics induces significant structural changes in the endolymphatic sac epithelium.
- These alterations are likely secondary to disruptions in inner ear fluid and ion balance rather than a direct toxic effect on the endolymphatic sac.