Morphological evidence of ototoxicity of the iron chelator deferoxamine.
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attenuation of gentamicin ototoxicity by iron chelators led us to re-examine experimental material from a previously unpublished study of deferoxamine.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.
Ryals
B
B
Department of Communication Sciences and Disorders, James Madison University, Harrisonburg, VA 22807, USA. ryalsbm@jmu.edu
Westbrook
E
E
Schacht
J
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D001489:Basilar Membrane / Q000187:drug effects / Q000473:pathology; D003370:Coturnix; D003676:Deferoxamine / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007758:Ear, Inner / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D005609:Free Radicals / Q000378:metabolism; D005839:Gentamicins / Q000633:toxicity; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male
D000900:Anti-Bacterial Agents; D005609:Free Radicals; D005839:Gentamicins; D007502:Iron Chelating Agents; D003676:Deferoxamine