A novel synthetic compound, 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione, inhibits cisplatin-induced hearing loss by the suppression of reactive oxygen species: In vitro and in vivo study

Highlights ► KR-22332 is a novel otoprotective synthetic compound against cisplatin-induced ototoxicity. ► KR-22332 protected auditory cells from cisplatin by blocking the change of MMP and ROS. ► KR-22332 inhibited the activation of MAPKs and inflammatory cytokines by cisplatin. ► Transtympanic adm...

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Bibliographic Details
Published in:Neuroscience 2013-03, Vol.232, p.1-12
Main Authors: Shin, Y.S, Song, S.J, Kang, S.U, Hwang, H.S, Choi, J.W, Lee, B.H, Jung, Y.-S, Kim, C.-H
Format: Article
Language:English
Subjects:
3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR-22332)
Animals
Apoptosis - drug effects
Apoptosis - physiology
Biological and medical sciences
Caspase 3 - metabolism
Cell Line
cisplatin
Cisplatin - toxicity
Drug toxicity and drugs side effects treatment
Ear and associated structures. Auditory pathways and centers. Hearing. Vocal organ. Phonation. Sound production. Echolocation
Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology
Evoked Potentials, Auditory, Brain Stem - drug effects
Evoked Potentials, Auditory, Brain Stem - physiology
Extracellular Signal-Regulated MAP Kinases - metabolism
Female
Fundamental and applied biological sciences. Psychology
Hearing Loss - physiopathology
Hearing Loss - prevention & control
hearing preservation
Medical sciences
Membrane Potential, Mitochondrial - drug effects
Membrane Potential, Mitochondrial - physiology
Mice
mitochondria
NADPH Oxidases - metabolism
Neurology
Neuroprotective Agents - chemistry
Neuroprotective Agents - pharmacology
Non tumoral diseases
Organ of Corti - drug effects
Organ of Corti - physiopathology
Otorhinolaryngology. Stomatology
ototoxicity
Pharmacology. Drug treatments
Quinolones - chemical synthesis
Quinolones - pharmacology
Rats, Sprague-Dawley
reactive oxygen species
Reactive Oxygen Species - metabolism
Toxicity: respiratory system, ent, stomatology
Tumor Necrosis Factor-alpha - metabolism
Tumor Suppressor Protein p53 - metabolism
Vertebrates: nervous system and sense organs
Zebrafish
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Summary:Highlights ► KR-22332 is a novel otoprotective synthetic compound against cisplatin-induced ototoxicity. ► KR-22332 protected auditory cells from cisplatin by blocking the change of MMP and ROS. ► KR-22332 inhibited the activation of MAPKs and inflammatory cytokines by cisplatin. ► Transtympanic administration of KR-22332 in a rat model was protective against cisplatin-induced hearing loss. ► KR-22332 can be delivered topically through the middle ear, minimizing systemic effects.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2012.12.008