[Protection of cochlear function from aminoglycosides ototoxicity by manganese superoxide dismutase gene in aging rat].
OBJECTIVE
determine the feasibility of manganese superoxide dismutase (MnSOD) gene therapy for protecting the cochlear function against aminoglycoside-induced oxidative stress in aging rats.


METHODS
The aging model of SD rats were obtained with 8 weeks daily of D-gal (150 mg/kg per day) hypodermic injection. In the 9th week, amikacin (500 mg/kg per day) were injected intramuscularly into some aging SD rats. The viral particles of recombinant adeno-associated viral vector II/MnSOD (6 microl, 5 x 10(11) vector genomes/ml) were injected into the perilymph through the round window membrane (RWM). The feasibility of MnSOD gene therapy against aminoglycoside-induced oxidative stress in aging rats was evaluated with the methods of caspase-3 protein analysis, apoptosis detection with immunohistochemical, the detection of MnSOD concentration, stretched preparation of basilar membrane and evaluation of hearing threshold with ABR-click.


RESULTS
Compared with the control group, the concentration of MnSOD of cochlear tissue was increased (P < 0.05), and the active fragment expression of caspase-3, the numbers of apoptosis bodies and the hearing threshold were decreased (P < 0.05).


CONCLUSIONS
MnSOD could play a partly role to treat cochlear aminoglycoside-induced oxidative damage in aging rats.
Yang
Yang
Y
Department of Otorhinolaryngology Head and Neck Surgery, Union Hospital of Tongji medical college, Huazhong University of Science and Technology, Wuhan 430022, China.
Kong
Wei-jia
WJ
Hu
Yu-juan
YJ
Li
Jun
J
Zhong
Yi
Y
Zhao
Xue-yan
XY
Hao
Ya-nan
YN
Peng
Wei
W
D000617:Aminoglycosides / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D003051:Cochlea / Q000378:metabolism / Q000473:pathology*; D000229:Dependovirus / Q000235:genetics; D007758:Ear, Inner / Q000166:cytology / Q000378:metabolism; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000235:genetics*; D014162:Transfection
D000617:Aminoglycosides; D013482:Superoxide Dismutase; C505410:Casp3 protein, rat; D053148:Caspase 3