國家衛生研究院 NHRI:Item 3990099045/10047
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    题名: Extracellular calcium concentration and channel activity involved in aminoglycoside-induced hair cell toxicity in the zebrafish lateral line
    作者: Chan, MH;Wu, CY;Liu, CF;Chen, HH
    贡献者: Center for Neuropsychiatric Research
    摘要: Introduction: Ototoxic damage often caused by antibiotic aminoglycosides leads to the loss of hair cells. Since aminoglycosides are effective at infection treatment, it is imperative to discover new approach to prevent hearing loss and permit safe use of aminoglycosides. The alterations in cytosolic calcium homeostasis play an important role in aminoglycoside-induced sensory hair cell death. However, the involvement of cytoplasmic membrane calcium channels in aminoglycoside ototoxicity is not clear. Objective: The present study determined the role of calcium and its channel activity in ototoxicity induced by aminoglycosides. Materials and methods: In this study, the lateral lines of zebrafish were used to investigate the effects of verapamil, a calcium channel blocker, and Bay K8644, a calcium channel activator, on aminoglycoside (neomycin and gentamycin)-induced hair cell toxicity which was detected in vivo by the dye FM1-43FX, a reliable indicator to assess hair cell viability. Results: The data showed that verapamil significantly attenuated both aminoglycosides induced hair cell loss, whereas Bay K8644 enhanced their ototoxicity. Interestingly, the loss of hair cells induced by both aminoglycosides was respectively reduced and reinforced under extracellular high calcium (3.3 mM) and low calcium (33 μM) concentrations compared with normal calcium (330 μM) condition. Furthermore, Bay K8644 partly inhibited the protective action of extracellular high calcium on hair cell death mediated by the aminoglycoside treatment. Conclusions: These findings indicate that both extracellular calcium concentration and calcium channel activity influence hair cell loss from aminoglycoside toxicity.
    日期: 2016-10-10
    關聯: Toxicology Letters. 2016 Oct 10;259(Suppl.):S202.
    Link to: http://dx.doi.org/10.1016/j.toxlet.2016.07.484
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0378-4274&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000396848100502
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