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Quinoxaline protects zebrafish lateral line hair cells from cisplatin and aminoglycosides damage

Hair cell (HC) death is the leading cause of hearing and balance disorders in humans. It can be triggered by multiple insults, including noise, aging, and treatment with certain therapeutic drugs. As society becomes more technologically advanced, the source of noise pollution and the use of drugs wi...

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Autores principales: Rocha-Sanchez, Sonia M., Fuson, Olivia, Tarang, Shikha, Goodman, Linda, Pyakurel, Umesh, Liu, Huizhan, He, David Z., Zallocchi, Marisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181994/
https://www.ncbi.nlm.nih.gov/pubmed/30310154
http://dx.doi.org/10.1038/s41598-018-33520-w
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author Rocha-Sanchez, Sonia M.
Fuson, Olivia
Tarang, Shikha
Goodman, Linda
Pyakurel, Umesh
Liu, Huizhan
He, David Z.
Zallocchi, Marisa
author_facet Rocha-Sanchez, Sonia M.
Fuson, Olivia
Tarang, Shikha
Goodman, Linda
Pyakurel, Umesh
Liu, Huizhan
He, David Z.
Zallocchi, Marisa
author_sort Rocha-Sanchez, Sonia M.
collection PubMed
description Hair cell (HC) death is the leading cause of hearing and balance disorders in humans. It can be triggered by multiple insults, including noise, aging, and treatment with certain therapeutic drugs. As society becomes more technologically advanced, the source of noise pollution and the use of drugs with ototoxic side effects are rapidly increasing, posing a threat to our hearing health. Although the underlying mechanism by which ototoxins affect auditory function varies, they share common intracellular byproducts, particularly generation of reactive oxygen species. Here, we described the therapeutic effect of the heterocyclic compound quinoxaline (Qx) against ototoxic insults in zebrafish HCs. Animals incubated with Qx were protected against the deleterious effects of cisplatin and gentamicin, and partially against neomycin. In the presence of Qx, there was a reduction in the number of TUNEL-positive HCs. Since Qx did not block the mechanotransduction channels, based on FM1-43 uptake and microphonic potentials, this implies that Qx’s otoprotective effect is at the intracellular level. Together, these results unravel a novel therapeutic role for Qx as an otoprotective drug against the deleterious side effects of cisplatin and aminoglycosides, offering an alternative option for patients treated with these compounds.
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spelling pubmed-61819942018-10-15 Quinoxaline protects zebrafish lateral line hair cells from cisplatin and aminoglycosides damage Rocha-Sanchez, Sonia M. Fuson, Olivia Tarang, Shikha Goodman, Linda Pyakurel, Umesh Liu, Huizhan He, David Z. Zallocchi, Marisa Sci Rep Article Hair cell (HC) death is the leading cause of hearing and balance disorders in humans. It can be triggered by multiple insults, including noise, aging, and treatment with certain therapeutic drugs. As society becomes more technologically advanced, the source of noise pollution and the use of drugs with ototoxic side effects are rapidly increasing, posing a threat to our hearing health. Although the underlying mechanism by which ototoxins affect auditory function varies, they share common intracellular byproducts, particularly generation of reactive oxygen species. Here, we described the therapeutic effect of the heterocyclic compound quinoxaline (Qx) against ototoxic insults in zebrafish HCs. Animals incubated with Qx were protected against the deleterious effects of cisplatin and gentamicin, and partially against neomycin. In the presence of Qx, there was a reduction in the number of TUNEL-positive HCs. Since Qx did not block the mechanotransduction channels, based on FM1-43 uptake and microphonic potentials, this implies that Qx’s otoprotective effect is at the intracellular level. Together, these results unravel a novel therapeutic role for Qx as an otoprotective drug against the deleterious side effects of cisplatin and aminoglycosides, offering an alternative option for patients treated with these compounds. Nature Publishing Group UK 2018-10-11 /pmc/articles/PMC6181994/ /pubmed/30310154 http://dx.doi.org/10.1038/s41598-018-33520-w Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Rocha-Sanchez, Sonia M.
Fuson, Olivia
Tarang, Shikha
Goodman, Linda
Pyakurel, Umesh
Liu, Huizhan
He, David Z.
Zallocchi, Marisa
Quinoxaline protects zebrafish lateral line hair cells from cisplatin and aminoglycosides damage
title Quinoxaline protects zebrafish lateral line hair cells from cisplatin and aminoglycosides damage
title_full Quinoxaline protects zebrafish lateral line hair cells from cisplatin and aminoglycosides damage
title_fullStr Quinoxaline protects zebrafish lateral line hair cells from cisplatin and aminoglycosides damage
title_full_unstemmed Quinoxaline protects zebrafish lateral line hair cells from cisplatin and aminoglycosides damage
title_short Quinoxaline protects zebrafish lateral line hair cells from cisplatin and aminoglycosides damage
title_sort quinoxaline protects zebrafish lateral line hair cells from cisplatin and aminoglycosides damage
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181994/
https://www.ncbi.nlm.nih.gov/pubmed/30310154
http://dx.doi.org/10.1038/s41598-018-33520-w
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