CYTOTOXIC AND MOLECULAR MECHANISMS IN OTOTOXICITY OF CISPLATIN

Authors : Dilek Ülker ÇAKIR, Zekiye ALTUN, Nur OLGUN

Pages : 43-60

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Publication Date : 2018-05-01

Article Type : Research Paper

Abstract :Ototoxicity is based on inner ear dysfunction creating hearing loss, balance disorder or both symptoms depending on the drug or chemical agent.    Genetic and nongenetic risk factors, in addition to dose and time, play important roles in cisplatin ototoxicity.Although the changes firstly begin from first line of outer hairy cells on the Corti organ in the inner ear and then progress. Though the effect on the spiral ganglion and stria vascularis in addition to the Corti organ are well-defined, the molecular mechanisms that cause hearing loss  are not fully understood. Cellular and molecular mechanisms and particularly apoptotic mechanisms explain cisplatin cytotoxicity leading to cochlea damage. DNA damage induced by cisplatin and ROS production seem to be mainly responsible for cisplatin toxicity. Children treated with cisplatin are at risk of early or late hearing loss which could affect learning, communication, school performance, social communication and general quality of life . For this reason, many protective agents are used with cisplatin without changing its antitumoral efficiency. Studies of compounds to prevent ototoxicity may provide compounds for use in routine clinical practice and prevent one of the major dose-limiting side effects of cisplatin therapy, which will increase treatment efficacy and improve patient quality of life.
Keywords : Ototoxicity, cisplatin, cellular, molecular, apoptotic mechanisms