Epicatechin protects auditory cells against cisplatin-induced death.
Cisplatin, a chemotherapeutic drug that is widely used to treat various cancers, promotes ototoxicity at higher doses. In this study, the effect of epicatechin (EC) on cisplatin-induced hair cell death was investigated in a cochlear organ of Corti-derived cell line, HEI-OC1, and in vivo in zebrafish. Cisplatin promoted apoptosis and altered mitochondrial membrane potential (MMP) in HEI-OC1 cells. EC inhibited cisplatin-induced apoptosis and intracellular reactive oxygen species (ROS) generation. Labeling of zebrafish lateral line hair cells by the fluorescent dye YO-PRO1 was lost upon exposure to cisplatin, and EC protected against this cisplatin-induced loss of labeling in a dose-dependent manner. Scanning and transmission electron micrographs showed that treatment with EC protected against cisplatin-induced loss of kinocilium and stereocilia in zebrafish neuromasts. These results suggest that EC prevents cisplatin-induced ototoxicity by blocking ROS generation and by preventing changes in MMP.
Kim
Chul-Ho
CH
Department of Otolaryngology, School of Medicine, Ajou University, 5 Wonchon-Dong, Yeongtong-Gu, Suwon 442-749, South Korea. ostium@ajou.ac.kr
Kang
Sung Un
SU
Pyun
JungHee
J
Lee
Mi Hye
MH
Hwang
Hye Sook
HS
Lee
HaNeul
H
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002392:Catechin / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects*; D006198:Hair Cells, Auditory / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015027:Zebrafish
D017382:Reactive Oxygen Species; D002392:Catechin; D053148:Caspase 3; D002945:Cisplatin