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Epicatechin protects the auditory organ by attenuating cisplatin-induced ototoxicity through inhibition of ERK.

Authors
Lee, JS; Kang, SU; Hwang, HS; Pyun, JH; Choung, YH; Kim, CH
Citation
Toxicology letters, 199(3):308-316, 2010
Journal Title
Toxicology letters
ISSN
0378-42741879-3169
Abstract
Cisplatin, a widely used chemotherapeutic drug, causes ototoxicity in a large percentage of patients. The purpose of this study was to determine the efficacy of epicatechin (EC) as an otoprotective agent to prevent cisplatin toxicity and to investigate the molecular mechanism of EC. The effects of EC on cisplatin-induced ototoxicity were investigated in a cochlear organ of Corti-derived cell line, HEI-OC1 and in a rat model. In addition, signaling mechanisms were investigated, specifically those involving MAP kinase. Cisplatin induced apoptosis and demonstrated, conjugation of annexin V/PI in FACS, and an increase of subG1 in HEI-OC1. EC protected HEI-OC1 against cisplatin and showed inhibition of cisplatin-induced apoptosis of the HEI-OC1 by transmission electron microscopy. Intratympanic administration of EC protected against cisplatin-induced ototoxicity in the rat model, as determined by auditory brainstem responses. EC inhibited activation of JNK, ERK, cytochrome-c and caspase-3 by cisplatin. An ERK Inhibitor, cisplatin-induced ototoxicity in a dose dependent manner but a JNK inhibitor did not. The results of this study suggest that EC may provide a mechanism by which ototoxicity caused by the administration of cisplatin can be reduced through the inhibition of ERK. EC may have clinical use as a chemopreventive agent that prevents cisplatin ototoxicity.
MeSH terms
AnimalsAntineoplastic Agents/*toxicityApoptosis/drug effectsCatechin/*pharmacologyCells, CulturedCisplatin/*toxicityCochlea/*drug effectsEvoked Potentials, Auditory, Brain Stem/drug effectsExtracellular Signal-Regulated MAP Kinases/*antagonists & inhibitorsFemaleHearing Loss/chemically inducedRatsRats, Sprague-Dawley
DOI
10.1016/j.toxlet.2010.09.013
PMID
20883750
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Otolaryngology
AJOU Authors
이, 진석정, 연훈김, 철호
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