Hwanggunchungyitang prevents cadmium-induced ototoxicity through suppression of the activation of caspase-9 and extracellular signal-related kinase in auditory HEI-OC1 cells.
Hwanggunchungyitang (HGCYT) is a newly designed herbal drug formula for the purpose of treating auditory diseases. A number of heavy metals have been associated with toxic effects to the peripheral or central auditory system. Cadmium (Cd(2+)) is a heavy metal and a potent carcinogen implicated in tumor development through occupational and environmental exposure. However, the auditory effect of Cd(2+) is not poorly understood. The purpose of the present study was to investigate whether HGCYT prevent the ototoxic effects induced by Cd(2+) in auditory cell line, HEI-OC1. HGCYT inhibited the cell death, reactive oxygen species generation (ROS), activation of caspase-9, and extracellular signal-related kinase (ERK) induced by Cd(2+). In addition, we observed that cochlear hair cells in middle turn were damaged by Cd(2+). However, HGCYT prevented the destruction of hair cell arrays of the rat primary organ of Corti explants in the presence of Cd(2+). These results support the notion that ROS are involved in Cd(2+) ototoxicity and suggest HGCYT therapeutic usefulness, against Cd(2+)-induced activation of caspase-9 and ERK.
Kim
Su-Jin
SJ
VestibuloCochlear Research Center of Wonkwang University, Jeonbuk, Republic of Korea.
Shin
Bong-Gi
BG
Choi
In-Young
IY
Kim
Dong-Hyun
DH
Kim
Min-Cheol
MC
Myung
Noh-Yil
NY
Moon
Phil-Dong
PD
Lee
Jeong-Han
JH
An
Hyo-Jin
HJ
Kim
Na-Hyung
NH
Lee
Joo-Young
JY
So
Hong-Seob
HS
Park
Rae-Kil
RK
Jeong
Hyun-Ja
HJ
Um
Jae-Young
JY
Kim
Hyung-Min
HM
Hong
Seung-Heon
SH
D000818:Animals; D015153:Blotting, Western; D002104:Cadmium / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity*; D053453:Caspase 9 / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006311:Hearing Disorders / Q000139:chemically induced* / Q000517:prevention & control*; D006801:Humans; D007202:Indicators and Reagents; D051379:Mice; D009924:Organ Culture Techniques; D009925:Organ of Corti / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles
D004365:Drugs, Chinese Herbal; D007202:Indicators and Reagents; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; C539018:hwanggunchungyitang; D002104:Cadmium; D048049:Extracellular Signal-Regulated MAP Kinases; D053453:Caspase 9; C022616:thiazolyl blue