Korean J Otorhinolaryngol-Head Neck Surg.  2012 Jan;55(1):1-7. 10.3342/kjorl-hns.2012.55.1.1.

Update of Research on Aminoglycoside Ototoxicity

• Byun JY

• KMID: 2277304
• DOI: http://doi.org/10.3342/kjorl-hns.2012.55.1.1

Abstract

It has long been known that the major irreversible toxicity of aminoglycosides is ototoxicity. Among them, streptomycin and gentamicin are primarily vestibulotoxic, whereas amikacin, neomycin, dihydrosterptomycin, and kanamicin are primarily cochleotoxic. Cochlear damage can produce permanent hearing loss, and damage to the vestibular apparatus results in dizziness, ataxia, and/or nystagmus. Therefore the cellular mechanisms of aminoglycoside ototoxicity continue to be an active topic of research. Aminoglycosides appear to generate free radicals within the inner ear and activation of the c-Jun N-terminal kinase. These changes lead to the release of cytochrome-c from mitochondria, activation of caspases and nucleases and appearance of pyknotic nuclei in hair cells with subsequent permanent damage to sensory cells and neurons, resulting in permanent hearing loss. Also two mutations in the mitochondrial 12S ribosomal RNA gene have been previously reported to predispose carriers to aminoglycoside induced ototoxicity. Over the years, understanding of the antimicrobial as well as ototoxic mechanisms of aminoglycosides has increased. Nevertheless, proven clinical methods for the prevention of ototoxic injury are not yet available. I reviewed these mechanisms in regard to established and potential future targets.

Keyword

Aminoglycoside; Hair cell; Ototoxicity; Mechanism

MeSH Terms

Amikacin
Aminoglycosides
Ataxia
Caspases
Dizziness
Ear, Inner
Free Radicals
Genes, rRNA
Gentamicins
Hair
Hearing Loss
JNK Mitogen-Activated Protein Kinases
Mitochondria
Neomycin
Neurons
Streptomycin
Vestibule, Labyrinth
Amikacin
Aminoglycosides
Caspases
Free Radicals
Gentamicins
JNK Mitogen-Activated Protein Kinases
Neomycin
Streptomycin