title: Vestibular damage in chronic ototoxicity: a mini-review.
abstract: Ototoxicity is a major cause of the loss of hearing and balance in humans. Ototoxic compounds include pharmaceuticals such as aminoglycoside antibiotics, anti-malarial drugs, loop diuretics and chemotherapeutic platinum agents, and industrial chemicals including several solvents and nitriles. Human and rodent data indicate that the main target of toxicity is hair cells (HCs), which are the mechanosensory cells responsible for sensory transduction in both the auditory and the vestibular system. Nevertheless, the compounds may also affect the auditory and vestibular ganglion neurons. Exposure to ototoxic compounds has been found to cause HC apoptosis, HC necrosis, and damage to the afferent terminals, of differing severity depending on the ototoxicity model. One major pathway frequently involved in HC apoptosis is the c-jun N-terminal kinase (JNK) signaling pathway activated by reactive oxygen species, but other apoptotic pathways can also play a role in ototoxicity. Moreover, little is known about the effects of chronic low-dose exposure. In rodent vestibular epithelia, extrusion of live HCs from the sensory epithelium may be the predominant form of cell demise during chronic ototoxicity. In addition, greater involvement of the afferent terminals may occur, particularly the calyx units contacting type I vestibular HCs. As glutamate is the neurotransmitter in this synapse, excitotoxic phenomena may participate in afferent and ganglion neuron damage. Better knowledge of the events that take place in chronic ototoxicity is of great interest, as it will increase understanding of the sensory loss associated with chronic exposure and aging.
authors: Department de Ciències Fisiològiques II, Universitat de Barcelona, 08907 Hospitalet de Llobregat, Catalonia, Spain.
authors: Lara
authors: L
authors: Sedó-Cabezón
authors: NEOMA Research Group, Departament de Ciències Mèdiques, Facultat de Medicina, Universitat de Girona, 17071 Girona, Catalonia, Spain.
authors: Pere
authors: P
authors: Boadas-Vaello
authors: Department de Ciències Fisiològiques II, Universitat de Barcelona, 08907 Hospitalet de Llobregat, Catalonia, Spain.
authors: Carla
authors: C
authors: Soler-Martín
authors: Department de Ciències Fisiològiques II, Universitat de Barcelona, 08907 Hospitalet de Llobregat, Catalonia, Spain; Institut d'Investigació Biomèdica de Bellvitge, IDIBELL, 08907 Hospitalet de Llobregat, Catalonia, Spain. Electronic address: jllorens@ub.edu.
authors: Jordi
authors: J
authors: Llorens
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000009:adverse effects*; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D018069:Hair Cells, Vestibular / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D015837:Vestibular Diseases / Q000139:chemically induced / Q000150:complications / Q000473:pathology
chemical_list: D000890:Anti-Infective Agents
keywords: Aminoglycoside antibiotics; Audiovestibular ganglion neurons; Hair cells; Inner ear; Nitriles; Ototoxicity