ArticleJCI insight2021
Characterization of quinoxaline derivatives for protection against iatrogenically induced hearing loss.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Experimental and Clinical Approaches to Preventing Aminoglycoside-Induced Ototoxicity: A Scoping Review.Antioxidants (Basel, Switzerland) · 2025Review
- CD38 Coordinates with NF-κB to Promote Cochlear Inflammation in Noise-Induced Hearing Loss: the Protective Effect of Apigenin.Molecular neurobiology · 2025Article
- Paving the way for better ototoxicity assessments in cisplatin therapy using more reliable animal models.Frontiers in cellular neuroscience · 2025Article
- Crosslinked-hybrid nanoparticle embedded in thermogel for sustained co-delivery to inner ear.Journal of nanobiotechnology · 2024Article
- Piplartine attenuates aminoglycoside-induced TRPV1 activity and protects from hearing loss in mice.Science translational medicine · 2024Article
- Chemical screen in zebrafish lateral line identified compounds that ameliorate neomycin-induced ototoxicity by inhibiting ferroptosis pathway.Cell & bioscience · 2024Article
- FDA-Approved Tedizolid Phosphate Prevents Cisplatin-Induced Hearing Loss Without Decreasing Its Anti-tumor Effect.Journal of the Association for Research in Otolaryngology : JARO · 2024Article
- Evaluation of Cisplatin-Induced Pathology in the Larval Zebrafish Lateral Line.International journal of molecular sciences · 2022Article
- Apigenin alleviates neomycin-induced oxidative damage via the Nrf2 signaling pathway in cochlear hair cells.Frontiers of medicine · 2022Article
- Hair cell toxicology: With the help of a little fish.Frontiers in cell and developmental biology · 2022Review
- Novel Application of Eupatilin for Effectively Attenuating Cisplatin-Induced Auditory Hair Cell Death via Mitochondrial Apoptosis Pathway.Oxidative medicine and cellular longevity · 2022Article
- AZD5438-PROTAC: A selective CDK2 degrader that protects against cisplatin- and noise-induced hearing loss.European journal of medicinal chemistry · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
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 quinoxaline-5-carboxylic acid (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, revealed 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 did we observe a partial blockage of the mechanotransduction channels. Finally, we assessed the regulation of the 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.