Protection of cochlear function from aminoglycosides ototoxicity by manganese superoxide dismutase gene in aging rat

Abstract

determine the feasibility of manganese superoxide dismutase (MnSOD) gene therapy for protecting the cochlear function against aminoglycoside-induced oxidative stress in aging rats. 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. 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). MnSOD could play a partly role to treat cochlear aminoglycoside-induced oxidative damage in aging rats.