Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Recently published
    • Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Recently published
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a letter
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need Help? E-mail the JCI Insight
  • Top
  • Abstract
  • Supplemental material
  • Version history
  • Article usage
  • Citations to this article
Advertisement

ResearchIn-Press PreviewNeuroscienceTherapeutics Open Access | 10.1172/jci.insight.141561

Characterization of quinoxaline derivatives for protection against iatrogenic-induced hearing loss

Marisa Zallocchi,1 Santanu Hati,1 Zhenhang Xu,1 William Hausman,1 Huizhan Liu,1 David Z. He,1 and Jian Zuo1

1Department of Biomedical Sciences, Creighton University, Omaha, United States of America

Find articles by Zallocchi, M. in: JCI | PubMed | Google Scholar |

1Department of Biomedical Sciences, Creighton University, Omaha, United States of America

Find articles by Hati, S. in: JCI | PubMed | Google Scholar

1Department of Biomedical Sciences, Creighton University, Omaha, United States of America

Find articles by Xu, Z. in: JCI | PubMed | Google Scholar

1Department of Biomedical Sciences, Creighton University, Omaha, United States of America

Find articles by Hausman, W. in: JCI | PubMed | Google Scholar

1Department of Biomedical Sciences, Creighton University, Omaha, United States of America

Find articles by Liu, H. in: JCI | PubMed | Google Scholar

1Department of Biomedical Sciences, Creighton University, Omaha, United States of America

Find articles by He, D. in: JCI | PubMed | Google Scholar |

1Department of Biomedical Sciences, Creighton University, Omaha, United States of America

Find articles by Zuo, J. in: JCI | PubMed | Google Scholar

Published January 21, 2021 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.141561.
Copyright © 2021, Zallocchi et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published January 21, 2021 - Version history
View PDF
Abstract

Hair cell loss is the leading cause of hearing and balance disorders in humans. It can be caused by many factors, including noise, aging, and therapeutic agents. Previous studies have shown the therapeutic potential of quinoxaline against drug-induced ototoxicity. Here, we screened a library of 68 quinoxaline derivatives for protection against aminoglycoside-induced damage of hair cells from the zebrafish lateral line. We identified Qx28 as the best quinoxaline derivative that provides robust protection against both aminoglycosides and cisplatin in zebrafish and mouse cochlear explants. FM1-43 and aminoglycoside uptake, as well as antibiotic efficacy studies, reveal that Qx28 is neither blocking the mechanotransduction channels nor interfering with aminoglycoside antibacterial activity, suggesting that it may be protecting the hair cells by directly counteracting the ototoxin’s mechanism of action. Only when animals were incubated with higher doses of Qx28 we observed a partial blockage of the mechanotransduction channels. Finally, we assessed the regulation of NF-κB pathway in vitro in mouse embryonic fibroblasts and in vivo in zebrafish larvae. Those studies showed that Qx28 protects hair cells by blocking NF-κB canonical pathway activation. Thus, Qx28 is a promising and versatile otoprotectant that can act across different species and toxins.

Graphical Abstract
graphical abstract
Supplemental material

View Supplemental figures and table

View

Version history
  • Version 1 (January 21, 2021): In-Press Preview

Article tools

  • View PDF
  • Download citation information
  • Send a letter
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need Help? E-mail the JCI Insight

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Supplemental material
  • Version history
Advertisement
Advertisement
Follow JCI Insight:
Copyright © 2021 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts