Aminoglycoside ototoxicity in three murine strains and effects on NKCC1 of stria vascularis.
BACKGROUND
After establishing a murine model of aminoglycoside antibiotic (AmAn) induced ototoxicity, the sensitivity of AmAn induced ototoxicity in three murine strains and the effect of kanamycin on the expression of Na-K-2Cl cotransporter-1 (NKCC1) in stria vascularis were investigated.


METHODS
C57BL/6J, CBA/CaJ, NKCC1(+/-) mice (24 of each strain) were randomly divided into four experimental groups: A: kanamycin alone; B: kanamycin plus 2, 3-dihydroxybenzoate; C: 2, 3-dihydroxybenzoate alone; and D: control group. Mice were injected with kanamycin or/and 2, 3-dihydroxybenzoate twice daily for 14 days. Auditory brainstem response (ABR) was measured and morphology of cochlea delineated with succinate dehydrogenase staining. Expression of NKCC1 in stria vascularis was detected immunohistochemically.


RESULTS
All three strains in groups A and B developed significant ABR threshold shifts (P < 0.01), which were accompanied by outer hair cell loss. NKCC1 expression in stria vascularis was the weakest in group A (A cf D, P < 0.01) and the strongest in groups C and D (P < 0.05). CBA/CaJ mice had the highest sensitivity to AmAn.


CONCLUSIONS
Administration of kanamycin established AmAn induced ototoxicity. Kanamycin inhibited the expression of NKCC1 in stria vascularis. 2, 3-dihydroxybenzoate attenuated AmAn induced ototoxicity-possibly by enhancing the expression of NKCC1. Age related hearing loss did not show additional sensitivity to AmAn induced ototoxicity in murine model.
Chu
Han-qi
HQ
Department of Otolaryngology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. qi7chu@163.com
Xiong
Hao
H
Zhou
Xiao-qin
XQ
Han
Fang
F
Wu
Zhen-gong
ZG
Zhang
Ping
P
Huang
Xiao-wen
XW
Cui
Yong-hua
YH
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001309:Auditory Threshold / Q000187:drug effects; D018069:Hair Cells, Vestibular / Q000187:drug effects; D007612:Kanamycin / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D028021:Sodium-Potassium-Chloride Symporters / Q000032:analysis / Q000187:drug effects*; D064506:Solute Carrier Family 12, Member 2; D013316:Stria Vascularis / Q000737:chemistry / Q000187:drug effects*
D000900:Anti-Bacterial Agents; C578878:Slc12a2 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D007612:Kanamycin