Protective effect of NecroX, a novel necroptosis inhibitor, on gentamicin-induced ototoxicity.
BACKGROUND
NecroX is a novel necrosis and necroptosis inhibitor that shows scavenger activity against mitochondrial reactive oxygen species (ROS) and cytoprotective activity against various insults. These findings raise the possibility of its protective effect in ototoxicity. This study was performed to investigate the protective effect of NecroX on gentamicin (GM)-induced hair cell loss in neonatal mouse cochlea cultures.


METHODS
The protective effects of NecroX were measured by phalloidin staining of cultures from postnatal day 2-3 mice with GM-induced hair cell loss. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to detect apoptosis. The radical-scavenging activity of NecroX was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay.


RESULTS
NecroX showed a significant and concentration-dependent protective effect against GM-induced hair cell loss, and hair cells retained their stereocilia well. NecroX decreased GM-induced apoptosis of hair cells as assessed by TUNEL staining. Additionally, NecroX showed direct radical scavenging activity in the DPPH assay.


CONCLUSIONS
In this study, we demonstrated the protective effect of NecroX on GM-induced hair cell loss in neonatal cochlea cultures, and suggest that it may be of therapeutic use in the treatment of drug-induced ototoxicity.
Department of Otolaryngology - Head and Neck Surgery, Soonchunhyang University College of Medicine, Seoul, South Korea.
Moo Kyun
MK
Park
Byung Don
BD
Lee
Sung Won
SW
Chae
Junhyuk
J
Chi
Seong Keun
SK
Kwon
Jae-Jun
JJ
Song
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D003051:Cochlea / Q000166:cytology / Q000187:drug effects*; D019610:Cytoprotection; D005839:Gentamicins / Q000009:adverse effects*; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000473:pathology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology*
D000975:Antioxidants; D005839:Gentamicins; D006576:Heterocyclic Compounds, 4 or More Rings; C574766:NecroX-5; D017382:Reactive Oxygen Species; D013450:Sulfones