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Journal of Zhejiang University SCIENCE B 2011 Vol.12 No.10 P.853-861


Ototoxic destruction by co-administration of kanamycin and ethacrynic acid in rats

Author(s):  Hong Liu, Da-lian Ding, Hai-yan Jiang, Xue-wen Wu, Richard Salvi, Hong Sun

Affiliation(s):  Center for Hearing and Deafness, University at Buffalo, State University of New York, New York 14214, USA, Department of Otolaryngology, the Third Xiangya Hospital of Central South University, Changsha 410013, China, Department of Otolaryngology, Xiangya Hospital of Central South University, Changsha 410008, China

Corresponding email(s):   dding@buffalo.edu

Key Words:  Ototoxicity, Ethacrynic acid, Kanamycin, Rat, Blood-cochlea barrier

Hong Liu, Da-lian Ding, Hai-yan Jiang, Xue-wen Wu, Richard Salvi, Hong Sun. Ototoxic destruction by co-administration of kanamycin and ethacrynic acid in rats[J]. Journal of Zhejiang University Science B, 2011, 12(10): 853-861.

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author="Hong Liu, Da-lian Ding, Hai-yan Jiang, Xue-wen Wu, Richard Salvi, Hong Sun",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

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%T Ototoxic destruction by co-administration of kanamycin and ethacrynic acid in rats
%A Hong Liu
%A Da-lian Ding
%A Hai-yan Jiang
%A Xue-wen Wu
%A Richard Salvi
%A Hong Sun
%J Journal of Zhejiang University SCIENCE B
%V 12
%N 10
%P 853-861
%@ 1673-1581
%D 2011
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1100040

T1 - Ototoxic destruction by co-administration of kanamycin and ethacrynic acid in rats
A1 - Hong Liu
A1 - Da-lian Ding
A1 - Hai-yan Jiang
A1 - Xue-wen Wu
A1 - Richard Salvi
A1 - Hong Sun
J0 - Journal of Zhejiang University Science B
VL - 12
IS - 10
SP - 853
EP - 861
%@ 1673-1581
Y1 - 2011
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1100040

It is well known that ethacrynic acid (EA) can potentiate the ototoxicity of aminoglycoside antibiotics (AmAn) such as kanamycin (KM), if they were applied at the same time. Currently, to create the model of EA-KM-induced cochlear lesion in rats, adult rats received a single injection of EA (75 mg/kg, intravenous injection), or followed immediately by KM (500 mg/kg, intramuscular injection). The hearing function was assessed by auditory brainstem response (ABR) measurement in response to click and/or tone bursts at 4, 8, 12, 16, 20, 24, and 32 kHz. The static microcirculation status in the stria vascularis after a single EA injection was evaluated with eosin staining. The pathological changes in cochlear and vestibular hair cells were also quantified after co-administration of EA and KM. After a single EA injection, blood flow in vessels supplying the stria vascularis rapidly diminished. However, the blood supply to the cochlear lateral wall partially recovered 5 h after EA treatment. Threshold changes in ABR were basically parallel to the microcirculation changes in stria vascularis after single EA treatment. Importantly, disposable co-administration of EA and KM resulted in a permanent hearing loss and severe damage to the cochlear hair cells, but spared the vestibular hair cells. Since the cochlear lateral wall is the important part of the blood-cochlea barrier, EA-induced anoxic damage to the epithelium of stria vascularis may enhance the entry of KM to the cochlea. Thus, experimental animal model of selective cochlear damage with normal vestibular systems can be reliably created through co-administration of EA and KM.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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