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아미노글리코사이드 이독성 연구의 최신경향

Update of Research on Aminoglycoside Ototoxicity

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대한이비인후과학회 (Korean Society of Otorhinolaryngology-Head and Neck Surgery)|2012.01|대한이비인후과학회지 두경부외과학 (Korean Journal of Otorhinolaryngology-Head and Neck Surgery)|제55권 제1호|pp. 1-7

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키워드

MechanismAminoglycosideOtotoxicityHair cell
주제분류이비인후과학

초록

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. Korean J Otorhinolaryngol-Head Neck Surg 2012;55:1-7

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. Korean J Otorhinolaryngol-Head Neck Surg 2012;55:1-7

참고문헌 (54)

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