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

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Abstract

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.

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Authors and Affiliations

  1. Center for Hearing and Deafness, University at Buffalo, State University of New York, New York, 14214, USA

    Hong Liu, Da-lian Ding, Hai-yan Jiang, Xue-wen Wu & Richard Salvi

  2. Department of Otolaryngology, the Third Xiangya Hospital of Central South University, Changsha, 410013, China

    Hong Liu, Da-lian Ding & Xue-wen Wu

  3. Department of Otolaryngology, Xiangya Hospital of Central South University, Changsha, 410008, China

    Da-lian Ding & Hong Sun

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  1. Hong Liu
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Correspondence to Da-lian Ding.

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Project (No. R01 DC006630) supported by the National Institutes of Health (NIH) of USA

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Liu, H., Ding, Dl., Jiang, Hy. et al. Ototoxic destruction by co-administration of kanamycin and ethacrynic acid in rats. J. Zhejiang Univ. Sci. B 12, 853–861 (2011). https://doi.org/10.1631/jzus.B1100040

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