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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Veröffentlicht in:	Neuroscience 2013-03, Vol.232, p.1-12
Hauptverfasser:	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:	Artikel
Sprache:	eng
Schlagworte:	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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Beschreibung
Zusammenfassung:	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