PUBLICATION

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

Authors: Sanchez, S.M.R., Fuson, O., Tarang, S., Goodman, L., Pyakurel, U., Liu, H., He, D.Z., Zallocchi, M.
ID: ZDB-PUB-181013-4
Date: 2018
Source: Scientific Reports 8: 15119 (Journal)
Registered Authors
Keywords: none
MeSH Terms: none
PubMed: 30310154 Full text @ Sci. Rep.

Abstract

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.

Errata / Notes

corrected by ZDB-PUB-190615-3

Genes / Markers

Figures

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Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB	chemical treatment by environment: cisplatin	Day 5	neuromast hair cell apoptotic process increased occurrence, abnormal	Fig. 6
AB	chemical treatment by environment: gentamycin	Day 5	neuromast hair cell apoptotic process increased occurrence, abnormal	Fig. 6
AB	chemical treatment by environment: gentamycin	Day 5	neuromast has fewer parts of type neuromast hair cell, abnormal	Fig. 4
AB	chemical treatment by environment: gentamycin	Day 5	neuromast malformed, abnormal	Fig. 4
AB	chemical treatment by environment: neomycin	Day 5	neuromast hair cell apoptotic process increased occurrence, abnormal	Fig. 6
AB	chemical treatment by environment: neomycin	Day 5	neuromast has fewer parts of type neuromast hair cell, abnormal	Fig. 5
AB	chemical treatment by environment: neomycin	Day 5	neuromast malformed, abnormal	Fig. 5
AB	chemical treatment by environment: quinoxaline	Day 5	neuromast hair cell detection of mechanical stimulus involved in sensory perception of sound occurrence, normal	Fig. 7
AB	chemical treatment by environment: cisplatin, chemical treatment by environment: quinoxaline	Day 5	neuromast hair cell apoptotic process normal occurrence, ameliorated	Fig. 6
AB	chemical treatment by environment: gentamycin, chemical treatment by environment: quinoxaline	Day 5	neuromast hair cell apoptotic process increased occurrence, ameliorated	Fig. 6

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
s273tTg	Tg(pou4f3:GAP-GFP)	Transgenic Insertion
th263b		Point Mutation	pcdh15a

Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
AB
pcdh15a^{th263b/th263b}
s273tTg

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-otof	monoclonal	otofa otofb	IgG2a	Mouse

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
GFP	EFG	GFP

Mapping

Sanchez et al., 2018 ZDB-PUB-181013-4 PMID:30310154

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

Sanchez et al., 2018

ZDB-PUB-181013-4
PMID:30310154