[Protection from noise-induced hearing loss by a nitric oxide synthase inhibitor and neurotrophin 3 in the guinea pig cochlea].
OBJECTIVE
To observe the protective effect of nitric oxide synthase inhibitor-N(G)-nitro-L-arginine methyl ester (L-NAME) with or without neurotrophin 3 (NT3) on hearing in acoustic trauma.


METHODS
Eighty pigmented male guinea pigs were randomly divided into two groups: sham-exposed group (n=20) and noise-exposed group. The latter was divided into three subgroups: saline group (n=20), L-NAME group (n=20) and L-NAME + NT3 group (n=20). Two days consecutively and 30 min before noise exposure (4 kHz octave band noise at 115 dB SPL for 5 h), subjects in L-NAME and L-NAME + NT3 groups received an intraperitoneal injection of 10 mg/kg; animals in saline group received the same dosage of physiological saline at the same time. Four days before noise exposure, NT3 in artificial perilymph was delivered to the right scala tympani via a mini-osmotic pump in noise + L-NAME + NT3 group. Auditory brainstem responses (ABR) were measured before and 10 days following noise exposure. The cochlear tissue was assayed for nitric oxide (NO) level 3 days after noise exposure. Protection was assessed physiologically by the change in ABR threshold shift, and histologically by outer hair cell (OHC) survival.


RESULTS
The hearing thresholds and the number of OHC were relatively stable in sham-exposed group. The obvious threshold shift and OHC loss were observed in the noise-exposed groups. The hearing thresholds, NO level of cochlear tissue and OHC loss in the noise + saline group were significantly higher than those in the noise + L-NAME group (P < 0.01) and noise + L-NAME + NT3 group (P < 0.01). NT3 provided an additive functional (P < 0.01), but not morphological protection with L-NAME (P = 0.095).


CONCLUSIONS
Compared to L-NAME alone, a combination of L-NAME and NT-3 can provide an additional protection against acoustic trauma in the guinea pig cochlear.
Diao
Ming-fang
MF
Center of Otorhinolaryngology of Chinese People's Liberation Army, Navy General Hospital, Beijing 100037, China.
Gao
Wen-yuan
WY
Sun
Jian-jun
JJ
Liu
Ya
Y
Chen
Dong-lan
DL
Jiang
Wei
W
Zhao
Jing
J
Chen
Xi
X
D000818:Animals; D003051:Cochlea / Q000187:drug effects* / Q000293:injuries; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects; D006317:Hearing Loss, Noise-Induced / Q000517:prevention & control; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D020933:Neurotrophin 3 / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D020933:Neurotrophin 3; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester