Are vestibular hair cells excited to death by aminoglycoside antibiotics?
Aminoglycoside antibiotics are commonly prescribed throughout the world for the treatment of serious gram-negative bacterial infections. However, their use is limited by nephrotoxicity and ototoxicity. Although the traditional explanation for their ototoxicity in cochlear and vestibular hair cells has been the inhibition of mitochondrial protein synthesis, evidence is accumulating to suggest that many aminoglycosides cause excitotoxicity in hair cells as a result of their agonist action at the polyamine site on the N- methyl-D-aspartate (NMDA) receptor. The aim of this minireview is to summarise and critically evaluate this evidence and to consider the therapeutic implications of this hypothesis.
Smith
P F
PF
Department of Pharmacology, School of Medical Sciences, University of Otago Medical School, Dunedin, New Zealand. paul.smith@stonebow.otago.ac.nz
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D016923:Cell Death; D018069:Hair Cells, Vestibular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015837:Vestibular Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D016194:Receptors, N-Methyl-D-Aspartate