Volume 884, Issue 1 p. 60-68

Acute and Chronic Effects of Aminoglycosides on Cochlear Hair Cells

JEAN-MARIE ARAN

Corresponding Author

JEAN-MARIE ARAN

INSERM EMI-99/27 “Biologie Cellulaire et Moléculaire l'Audition,” Université Victor Ségalen Bordeaux 2, Hôpital Pellegrin, Bordeaux, France

a To whom correspondence may be addressed. Phone: 33 556 24 20 47; fax:33 556 96 29 84; e-mail: [email protected]Search for more papers by this author
JEAN-PAUL ERRE

JEAN-PAUL ERRE

INSERM EMI-99/27 “Biologie Cellulaire et Moléculaire l'Audition,” Université Victor Ségalen Bordeaux 2, Hôpital Pellegrin, Bordeaux, France

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DEISE LIMA DA COSTA

DEISE LIMA DA COSTA

INSERM EMI-99/27 “Biologie Cellulaire et Moléculaire l'Audition,” Université Victor Ségalen Bordeaux 2, Hôpital Pellegrin, Bordeaux, France

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IKRAM DEBBARH

IKRAM DEBBARH

INSERM EMI-99/27 “Biologie Cellulaire et Moléculaire l'Audition,” Université Victor Ségalen Bordeaux 2, Hôpital Pellegrin, Bordeaux, France

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DIDIER DULON

DIDIER DULON

INSERM EMI-99/27 “Biologie Cellulaire et Moléculaire l'Audition,” Université Victor Ségalen Bordeaux 2, Hôpital Pellegrin, Bordeaux, France

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First published: 06 February 2006
Citations: 41

Abstract

ABSTRACT: The first detectable effect on the auditory system after a single high-dose injection of an aminoglycosidic antibiotic (AA) like gentamicin (GM) is the reversible blockade of medial efferent function, probably via blockade of calcium channels at the base of the outer hair cells (OHC). The kinetics of this effect are compatible with that of the molecule in perilymph. In the course of chronic treatment with lower doses, however, ototoxicity develops only after several days of treatment. Still GM can be observed inside the OHCs as soon as 24 hours after the first injection, and will be still present in some OHCs as long as 11 months after a chronic, nonototoxic 6-day treatment.

In vitro, the short-term viability of isolated OHCs is not affected by exposure to AAs, but their transduction channels and their response to acetylcholine are reversibly blocked. However, developing organs of Corti in culture are highly and rapidly affected by exposure to AAs. Yet during direct intracochlear perilymphatic perfusion of GM, 2-mM solutions are not ototoxic, and with perfusion with a 20-mM solution ototoxicity develops only after several days of perfusion.

From these various observations one can describe some aspects of the mechanisms of ototoxicity of AAs, from their access to perilymph and endolymph, to penetration in the hair cells, likely via endocytosis at their apical pole, and intracellular cytotoxic events.