title: Aminoglycoside ototoxicity in three murine strains and effects on NKCC1 of stria vascularis.
abstract: 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.
authors.affiliation: Department of Otolaryngology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. qi7chu@163.com
authors.forename: Han-qi
authors.initials: HQ
authors.lastname: Chu
authors.forename: Hao
authors.initials: H
authors.lastname: Xiong
authors.forename: Xiao-qin
authors.initials: XQ
authors.lastname: Zhou
authors.forename: Fang
authors.initials: F
authors.lastname: Han
authors.forename: Zhen-gong
authors.initials: ZG
authors.lastname: Wu
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Xiao-wen
authors.initials: XW
authors.lastname: Huang
authors.forename: Yong-hua
authors.initials: YH
authors.lastname: Cui
mesh_terms: 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*
chemical_list: D000900:Anti-Bacterial Agents; C578878:Slc12a2 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D007612:Kanamycin