Mechanisms of cisplatin-induced ototoxicity and prevention.
Cisplatin is a widely used chemotherapeutic agent to treat malignant disease. Unfortunately, ototoxicity occurs in a large percentage of patients treated with higher dose regimens. In animal studies and in human temporal bone investigations, several areas of the cochlea are damaged, including outer hair cells in the basal turn, spiral ganglion cells and the stria vascularis, resulting in hearing impairment. The mechanisms appear to involve the production of reactive oxygen species (ROS), which can trigger cell death. Approaches to chemoprevention include the administration of antioxidants to protect against ROS at an early stage in the ototoxic pathways and the application of agents that act further downstream in the cell death cascade to prevent apoptosis and hearing loss. This review summarizes recent data that shed new light on the mechanisms of cisplatin ototoxicity and its prevention.
Rybak
Leonard P
LP
Department of Surgery, Division of Otolaryngology, Southern Illinois University, School of Medicine, P.O. Box 19653, Springfield, IL 62794-9653, USA. lrybak@siumed.edu
Whitworth
Craig A
CA
Mukherjea
Debashree
D
Ramkumar
Vickram
V
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D000975:Antioxidants / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004347:Drug Interactions; D034381:Hearing Loss / Q000139:chemically induced; D006801:Humans; D008954:Models, Biological; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects
D000970:Antineoplastic Agents; D000975:Antioxidants; D052247:Nitric Oxide Synthase Type II; D002945:Cisplatin