title: Salicylate initiates apoptosis in the spiral ganglion neuron of guinea pig cochlea by activating caspase-3.
abstract: Salicylate-induced ototoxicity leading to sensorineural hearing loss (SNHL) and tinnitus is well documented. However, the exact mechanisms are poorly defined. Caspase-3 is a member of the class of effector caspases and has been activated in nearly every model of apoptosis. To examine its role in salicylate-induced injury, we subjected guinea pigs to treatment with a specific inhibitor zDEVD-FMK via the round window niche (RWN) followed by a systemic injection of salicylate at a dose of 200 mg · kg(-1) · d(-1) i.p. for 10 consecutive days. For those animals administered with salicylate, immunohistochemical studies revealed that caspase-3 was activated in the spiral ganglion neurons (SGNs) and method of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) to identify neuronal apoptosis showed that fragmented nuclei were distributed in Rosenthal's canal. Topical administration of the zDEVD-FMK at a concentration of 500 mM blocked caspase-3 activation and had an effect in reducing the number of TUNEL-positive auditory neurons. In contrast, the inhibitor at a concentration of 125 or 250 mM caused no variation in the expression of activated caspase-3, or in the ratio of TUNEL-positive neurons. These results indicate that caspase-3 is a crucial mediator of apoptosis induced by salicylate in the primary auditory neuron in vivo, and suggest that the specific inhibitor at a relatively high concentration may be therapeutically beneficial in salicylate-induced apoptosis.
authors: Department of Otorhinolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, 22# Shuangyong Road, 530021 Nanning, Guangxi, People's Republic of China.
authors: Hao
authors: H
authors: Feng
authors: Shi-Hua
authors: SH
authors: Yin
authors: An-Zhou
authors: AZ
authors: Tang
authors: Song-Hua
authors: SH
authors: Tan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D003051:Cochlea / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D006168:Guinea Pigs; D020156:Salicylic Acid / Q000494:pharmacology*
chemical_list: D053148:Caspase 3; D020156:Salicylic Acid