title: Cobalt-Induced Ototoxicity in Rat Postnatal Cochlear Organotypic Cultures.
abstract: Cobalt (Co) is a required divalent metal used in the production of metal alloys, batteries, and pigments and is a component of vitamin B12. Excessive uptake of Co is neurotoxic causing temporary or permanent hearing loss; however, its ototoxic effects on the sensory hair cells, neurons, and support cells in the cochlea are poorly understood. Accordingly, we treated postnatal day 3 rat cochlear organotypic cultures with various doses and durations of CoCl2 and quantified the damage to the hair cells, peripheral auditory nerve fibers, and spiral ganglion neurons (SGN). Five-day treatment with 250 μM CoCl2 caused extensive damage to hair cells and neurons which increased with dose and treatment duration. CoCl2 caused greater damage to outer hair cells than inner hair cells; damage was greatest in the base of the cochlea and decreased towards the base. CoCl2 increased expression of superoxide radical in hair cells and SGNs and SGN loss was characterized by nuclear condensation and fragmentation, morphological features of apoptosis. CoCl2 treatment increased the expression of caspase-3 indicative of caspase-mediated programmed cell death. These results identify hair cells and spiral ganglion neurons as the main targets of Co ototoxicity in vitro and implicate the superoxide radical as a trigger of caspase-mediated ototoxicity.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guang Zhou, 510630, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Dalian
authors.initials: D
authors.lastname: Ding
authors.forename: Richard
authors.initials: R
authors.lastname: Salvi
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Roth
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D003035:Cobalt / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D009475:Neurons, Afferent / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009924:Organ Culture Techniques; D010784:Photomicrography; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000633:toxicity; D013997:Time Factors
chemical_list: D013481:Superoxides; D003035:Cobalt; C505410:Casp3 protein, rat; D053148:Caspase 3