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Novel synthetic protective compound, KR-22335, against cisplatin-induced auditory cell death.

DC Field Value Language
dc.contributor.authorShin, YS-
dc.contributor.authorSong, SJ-
dc.contributor.authorKang, S-
dc.contributor.authorHwang, HS-
dc.contributor.authorJung, YS-
dc.contributor.authorKim, CH-
dc.date.accessioned2016-11-09T04:59:26Z-
dc.date.available2016-11-09T04:59:26Z-
dc.date.issued2014-
dc.identifier.issn0260-437X-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/12810-
dc.description.abstractCisplatin [cis-diammine-dichloroplatinum (II)] is a widely used chemotherapeutic

agent, and one of its most severe side effects is ototoxicity. In the course of

developing a new protective agent against cisplatin-induced ototoxicity, we have

been interested in a novel synthetic compound,

3-Amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR-22335). We evaluated the

effectiveness of KR-22335 as an otoprotective agent against cisplatin-induced

toxicity. The otoprotective effect of KR-22335 against cisplatin was tested in

vitro in cochlear organs of Corti-derived cell lines, HEI-OC1, and in vivo in a

zebrafish (Danio rerio) model. Cisplatin-induced apoptosis, cell cycle arrest and

an increase in intracellular reactive oxygen species (ROS) generation were

demonstrated in HEI-OC1 cells. KR-22335 inhibited cisplatin-induced apoptosis and

mitochondrial injury in HEI-OC1 cells. KR-22335 inhibited cisplatin-induced

activation of JNK, p-38, caspase-3 and PARP in HEI-OC1 cells. Scanning and

transmission electron micrographs showed that KR-22335 prevented

cisplatin-induced destruction of kinocilium and stereocilia in zebrafish

neuromasts. Tissue TUNEL of neuromasts in zebrafish demonstrated that KR-22335

blocked cisplatin-induced TUNEL positive hair cells in neuromasts. The results of

this study suggest that KR-22335 may prevent ototoxicity caused by the

administration of cisplatin through the inhibition of mitochondrial dysfunction

and suppression of ROS generation. KR-22335 may be considered as a potential

candidate for protective agents against cisplatin-induced ototoxicity.
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dc.language.isoen-
dc.subject.MESHAnimals-
dc.subject.MESHAntineoplastic Agents-
dc.subject.MESHApoptosis-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHCisplatin-
dc.subject.MESHHair Cells, Auditory-
dc.subject.MESHHumans-
dc.subject.MESHIn Situ Nick-End Labeling-
dc.subject.MESHOxidative Stress-
dc.subject.MESHMitochondria-
dc.subject.MESHProtective Agents-
dc.subject.MESHQuinolones-
dc.subject.MESHReactive Oxygen Species-
dc.subject.MESHZebrafish-
dc.titleNovel synthetic protective compound, KR-22335, against cisplatin-induced auditory cell death.-
dc.typeArticle-
dc.identifier.pmid23297007-
dc.identifier.urlhttp://onlinelibrary.wiley.com/doi/10.1002/jat.2852/abstract;jsessionid=D45533E3B2A7015ED3F4C6EFDC0B51BD.f04t03-
dc.contributor.affiliatedAuthor신, 유섭-
dc.contributor.affiliatedAuthor강, 성운-
dc.contributor.affiliatedAuthor김, 철호-
dc.type.localJournal Papers-
dc.identifier.doi10.1002/jat.2852-
dc.citation.titleJournal of applied toxicology : JAT-
dc.citation.volume34-
dc.citation.number2-
dc.citation.date2014-
dc.citation.startPage191-
dc.citation.endPage204-
dc.identifier.bibliographicCitationJournal of applied toxicology : JAT, 34(2). : 191-204, 2014-
dc.identifier.eissn1099-1263-
dc.relation.journalidJ00260437X-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Otolaryngology
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