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Morphological evidence of ototoxicity of the iron chelator deferoxamine
B Ryals1, E Westbrook, J Schacht
1Department of Communication Sciences and Disorders, James Madison University, Harrisonburg, VA 22807, USA. ryalsbm@jmu.edu
Abstract:
Recent reports of the role of iron-catalyzed free radical formation in gentamicin ototoxicity and the successful attenuation of gentamicin ototoxicity by iron chelators led us to re-examine experimental material from a previously unpublished study of deferoxamine. Deferoxamine was injected i.m. into adult Japanese quail at either 300 or 750 mg/kg body weight for 30 days. Examination of sections from the basilar papilla at the light microscope level indicated that supporting cells were damaged after the lower drug dose, and that both supporting cells and hair cells were damaged after the higher drug dose. High, prolonged exposure to deferoxamine produced pathological changes similar to those seen in the basilar papilla after much lower, shorter doses of gentamicin. These results demonstrate that deferoxamine damages the quail inner ear and are consistent with the idea that the ototoxic actions of gentamicin may be mediated by iron chelation.
Insights
Deferoxamine, an iron chelator, caused damage to the inner ear in Japanese quail, similar to gentamicin ototoxicity. This suggests iron chelation may mediate gentamicin-induced hearing damage.
Area of Science:
- Ototoxicity research
- Inner ear pathology
- Pharmacology
Background:
- Gentamicin ototoxicity is linked to iron-catalyzed free radical formation.
- Iron chelators have shown potential in mitigating gentamicin-induced hearing damage.
- Previous unpublished data on deferoxamine's effects warranted re-examination.
Purpose of the Study:
- To investigate the ototoxic effects of deferoxamine in adult Japanese quail.
- To explore the role of iron chelation in gentamicin ototoxicity.
Main Methods:
- Deferoxamine was administered intramuscularly to Japanese quail at 300 or 750 mg/kg for 30 days.
- Light microscopy was used to examine tissue sections from the basilar papilla.
- Pathological changes in supporting cells and hair cells were assessed.
Main Results:
- Lower deferoxamine dose (300 mg/kg) damaged supporting cells in the basilar papilla.
- Higher deferoxamine dose (750 mg/kg) damaged both supporting cells and hair cells.
- Pathological changes resembled those induced by gentamicin.
Conclusions:
- Deferoxamine demonstrably damages the inner ear of Japanese quail.
- These findings support the hypothesis that iron chelation is involved in gentamicin ototoxicity.
- Iron chelation may be a key mechanism underlying gentamicin-induced hearing loss.