title: Ototoxicity: mechanisms of cochlear impairment and its prevention.
abstract: Aminoglycosides, cisplatin, and non-steroidal anti-inflammatory drugs (NSAIDs) are widely used pharmacological agents. There is a possibility, however, that the use of these agents may induce transient or permanent hearing loss and tinnitus as side effects. Recent animal studies have clarified mechanisms leading to the ototoxicity induced by these agents, at least in part. The permanent hearing loss caused by aminoglycosides and cisplatin is suggested to be predominantly associated with the apoptotic death of outer hair cells. Both drugs generate reactive oxygen species (ROS) in the inner ear. ROS can activate cell-death pathways such as the c-Jun Nterminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways, which in turn, induce hair cell apoptosis. On the other hand, the abuse of NSAIDs may transiently cause tinnitus and mild to moderate hearing loss. NSAIDs impair the active process of the outer hair cells and affect peripheral and central auditory neurons. Conversely, recent reports clarified that NSAIDs are potential therapeutic agents against cochlear injuries. In this review, recent findings from animal studies regarding the ototoxicity induced by aminoglycosides, cisplatin, and NSAIDs are summarized. Their ototoxic mechanisms are focused on.
authors.affiliation: Department of Otolaryngology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan. ktabuchi@md.tsukuba.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Tabuchi
authors.forename: B
authors.initials: B
authors.lastname: Nishimura
authors.forename: M
authors.initials: M
authors.lastname: Nakamagoe
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: M
authors.initials: M
authors.lastname: Nakayama
authors.forename: A
authors.initials: A
authors.lastname: Hara
mesh_terms: D000617:Aminoglycosides / Q000009:adverse effects / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000494:pharmacology*; D002945:Cisplatin / Q000009:adverse effects / Q000494:pharmacology; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism; D034381:Hearing Loss / Q000209:etiology* / Q000517:prevention & control*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D000893:Anti-Inflammatory Agents; D017382:Reactive Oxygen Species; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002945:Cisplatin