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시스플라틴 이독성 난청: 분자 메커니즘에 대한 최신 지견

Cisplatin-Induced Ototoxicity: Updates on Potential Molecular Mechanism

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대한이비인후과학회 (Korean Society of Otorhinolaryngology-Head and Neck Surgery)|2022.10|대한이비인후과학회지 두경부외과학 (Korean Journal of Otorhinolaryngology-Head and Neck Surgery)|제65권 제10호|pp. 569-579|DOI https://doi.org/10.3342/kjorl-hns.2022.00507

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키워드

MechanismCisplatinOtotoxicity
주제분류이비인후과학

초록

Cis-diamminedichloroplatinum(II) (cisplatin), platinum compound, is an anti-cancer agentcurrently used for the treatment of a number of human solid cancers. It irreversibly reacts withDNA to form an interconnection between guanine-group helices, resulting in cell death. Furthermore,it is also associated with numerous adverse effects such as nephrotoxicity, neurotoxicity,and ototoxicity. Hearing loss due to cisplatin ototoxicity is usually permanent and bilateral. Many studies have been conducted on the ototoxicity of cisplatin, however, its pathologyand treatment have not been fully elucidated. Studies have reported that cisplatin inhibits theaction of adenylate cyclase in the stria vascularis, and hearing loss occurs due to a decrease inthe receptor current of the outer hair cells. In addition, it has been reported that morphologicalchanges in the inner ear include changes in outer hair cells and abnormal findings in the supportingcells of the organ of Corti and Reissner’s membrane. Oxidative stress is known to bethe main cause of ototoxicity. In addition, it has recently been suggested that inflammationmay trigger inner ear cell death through autophagy, necrosis, and endogenous apoptosis. Inthis review, we intend to provide a basis for the prevention strategy of cisplatin-induced ototoxicityby revealing its molecular targets and intracellular pathways.

Abstract

Cis-diamminedichloroplatinum(II) (cisplatin), platinum compound, is an anti-cancer agentcurrently used for the treatment of a number of human solid cancers. It irreversibly reacts withDNA to form an interconnection between guanine-group helices, resulting in cell death. Furthermore,it is also associated with numerous adverse effects such as nephrotoxicity, neurotoxicity,and ototoxicity. Hearing loss due to cisplatin ototoxicity is usually permanent and bilateral. Many studies have been conducted on the ototoxicity of cisplatin, however, its pathologyand treatment have not been fully elucidated. Studies have reported that cisplatin inhibits theaction of adenylate cyclase in the stria vascularis, and hearing loss occurs due to a decrease inthe receptor current of the outer hair cells. In addition, it has been reported that morphologicalchanges in the inner ear include changes in outer hair cells and abnormal findings in the supportingcells of the organ of Corti and Reissner’s membrane. Oxidative stress is known to bethe main cause of ototoxicity. In addition, it has recently been suggested that inflammationmay trigger inner ear cell death through autophagy, necrosis, and endogenous apoptosis. Inthis review, we intend to provide a basis for the prevention strategy of cisplatin-induced ototoxicityby revealing its molecular targets and intracellular pathways.

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