Caspase-3 activation in the guinea pig cochlea exposed to salicylate.
In the current study, we explored whether chronic salicylate exposure could induce apoptosis in outer hair cells (OHCs) and spiral ganglion neurons (SGNs) of the cochlea. Guinea pig received sodium salicylate (400 mg/kg/d) or saline vehicle for 10 consecutive days. Programmed cell death (PCD) executioner was evaluated with immunohistochemistry detection of activated caspase-3. Apoptosis was examined with a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. Repeated salicylate administration activated caspase-3 and caused apoptosis in OHCs and SGNs (p<0.01 vs. saline control for both measures and in both cell types). Cell counting showed a significant loss in OHCs (p<0.01 vs. saline control), but not in inner hair cells (IHCs). Transmission electron microscopy (TEM) revealed chromatin condensation and nucleus margination in salicylate-treated cochlea. Scanning electron microscopy (SEM) demonstrated stereociliary bundles breakdown and fusion at the apical of OHCs, villous matter was discovered to attach on the surface of SGNs. These findings suggest that long-term administration of high-dose salicylate can activate caspase-3 pathway to induce OHC and SGN apoptosis.
Feng
Hao
H
Department of Otorhinolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China.
Yin
Shi-Hua
SH
Tang
An-Zhou
AZ
Cai
Hong-Wu
HW
Chen
Ping
P
Tan
Song-Hua
SH
Xie
Li-Hong
LH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism*; D002452:Cell Count; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002491:Central Nervous System Agents / Q000633:toxicity*; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D012980:Sodium Salicylate / Q000633:toxicity*; D013136:Spiral Ganglion / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D002491:Central Nervous System Agents; D002843:Chromatin; D053148:Caspase 3; D012980:Sodium Salicylate