[Kanamycin induced ototoxicity in three kinds of mouse strains and its effects on the expression of na-K-2Cl co-transporter-1 in stria vascularis].
OBJECTIVE
To establish a mice model of aminoglycoside antibiotics (AmAn) induced ototoxicity. Then to investigate the sensitivity of AmAn induced ototoxicity in three mouse strains and effect of kanamycin on the expression of Na-K-2Cl co-transporter-1 (NKCC1) in stria vascularis.


METHODS
C57BL/ 6J, CBA/CaJ, NKCC1 +/- mice (each of twenty-four) were randomly divided into four experimental groups A, B, C and D (A kanamycin alone, B kanamycin plus 2, 3-dihydroxybenzoate, C 2, 3-dihydroxybenzoate alone, D control group). Mice were injected with kanamycin or/and 2, 3-dihydroxybenzoate for 14 days. Auditory function was measured by auditory brainstem response (ABR) and morphology of cochlea was observed by succinate dehydrogenase staining. Expression of NKCC1 was detected by immunohistochemistry.


RESULTS
Mice in group A developed significant ABR threshold shifts (P < 0.01), which were accompanied by out hair cells loss. Mice in group B significantly attenuated ABR threshold shifts with out hair cells loss (P <0.01). The immunostaining of NKCC1 in stria vascularis was attenuated significantly in group A compared with group D (P < 0.01) while the immunostaining in group B was enhanced than which in group A (P < 0.01). CBA/CaJ mice has the highest sensitivity to AmAn in three mouse strains.


CONCLUSIONS
An mouse model of AmAn induced ototoxicity could be established by administration of kanamycin. Kanamycin could inhibit the expression of NKCC1 in stria vascularis. 2, 3-dihydroxybenzoate could attenuate AmAn induced ototoxicity maybe by enhancing the expression of NKCC1. Mice that had the characteristic of presbycusis didn't show additional sensitivity of AmAn induced ototoxicity.
Xiong
Hao
H
Department of Otolaryngology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China.
Chu
Han-Qi
HQ
Han
Fang
F
Wu
Zhen-Gong
ZG
Zhang
Ping
P
Wang
Chun-Fang
CF
Cui
Yong-Huo
YH
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism*; D003051:Cochlea / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D007612:Kanamycin / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010226:Parabens / Q000633:toxicity*; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D064506:Solute Carrier Family 12, Member 2
D000900:Anti-Bacterial Agents; D010226:Parabens; C578878:Slc12a2 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D007612:Kanamycin