title: Neurotoxicity of trimethyltin in rat cochlear organotypic cultures.
abstract: Trimethyltin (TMT), which has a variety of applications in industry and agricultural, is a neurotoxin that is known to affect the auditory system as well as central nervous system of humans and experimental animals. However, the mechanisms underlying TMT-induced auditory dysfunction are poorly understood. To gain insights into the neurotoxic effect of TMT on the peripheral auditory system, we treated cochlear organotypic cultures with concentrations of TMT ranging from 5 to 100 μM for 24 h. Interestingly, TMT preferentially damaged auditory nerve fibers and spiral ganglion neurons in a dose-dependent manner, but had no noticeable effects on the sensory hair cells at the doses employed. TMT-induced damage to auditory neurons was associated with significant soma shrinkage, nuclear condensation, and activation of caspase-3, biomarkers indicative of apoptotic cell death. Our findings show that TMT is exclusively neurotoxicity in rat cochlear organotypic culture and that TMT-induced auditory neuron death occurs through a caspase-mediated apoptotic pathway.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
authors.forename: Jintao
authors.initials: J
authors.lastname: Yu
authors.forename: Dalian
authors.initials: D
authors.lastname: Ding
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
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; D053148:Caspase 3 / Q000378:metabolism; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism; D003056:Cochlear Nerve / Q000187:drug effects*; D006198:Hair Cells, Auditory / Q000187:drug effects; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D014298:Trimethyltin Compounds / Q000633:toxicity*
chemical_list: D014298:Trimethyltin Compounds; C046488:trimethyltin; D053148:Caspase 3