Protective effect of NecroX, a novel necroptosis inhibitor, on gentamicin-induced ototoxicity

Abstract

Introduction: 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. Materials and 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-dipheny1-2-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 druginduced ototoxicity. (c) 2012 Elsevier Ireland Ltd. All rights reserved.