Aminoglycoside ototoxicity in three murine strains and effects on NKCC1 of stria vascularis
- Author:
- No author available
- Journal Title:
- CHINESE MEDICAL JOURNAL
- Issue:
- 12
- DOI:
- No doi available
- Key Word:
- kanamycin;2,3-dihydroxybenzoate;ototoxicity;reactive oxygen species;hearing loss
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-2C1 cotransporter-1 (NKCC 1) 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. NKCC 1 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 ototoxicitypossibly by enhancing the expression of NKCC1. Age related hearing loss did not show additional sensitivity to AmAn induced ototoxicity in murine model.
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