title: Reactive oxygen species in apoptosis induced by cisplatin: review of physiopathological mechanisms in animal models.
abstract: Cisplatin is a highly effective chemotherapeutic agent but displays significant ototoxic side effects. The most prominent change seen in the cochlea after cisplatin administration consists of loss of outer hair cells. Several mechanisms are believed to mediate cisplatin-induced apoptosis: binding of cisplatin to guanine bases on DNA and the formation of inter- and intra-strand chain cross-linking, generation of reactive oxygen species (ROS) with increased lipid peroxidation and Ca(2+) influx and, finally, inflammation mediated by cisplatin. The aim of the present review is to analyze the role of ROS in the mechanisms causing cisplatin-mediated apoptosis in the inner ear and the contribution of the different pathways involved, emphasizing the main strategies to blockade events leading to apoptosis of cochlear cells.
authors.affiliation: Department of Otorhinolaryngology, Otology Research Group, University Hospital of Puerta de Hierro-Majadahonda, Manuel de Falla 1, Majadahonda, 28222 Madrid, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Casares
authors.forename: Rafael
authors.initials: R
authors.lastname: Ramírez-Camacho
authors.forename: Almudena
authors.initials: A
authors.lastname: Trinidad
authors.forename: Amaya
authors.initials: A
authors.lastname: Roldán
authors.forename: Eduardo
authors.initials: E
authors.lastname: Jorge
authors.forename: José Ramón
authors.initials: JR
authors.lastname: García-Berrocal
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects*; D002945:Cisplatin / Q000009:adverse effects*; D003051:Cochlea / Q000187:drug effects; D007758:Ear, Inner / Q000187:drug effects*; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects; D007249:Inflammation / Q000209:etiology; D023421:Models, Animal; D017382:Reactive Oxygen Species / Q000009:adverse effects*
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D002945:Cisplatin