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Hwanggunchungyitang prevents cadmium-induced ototoxicity through suppression of the activation of caspase-9 and extracellular signal-related kinase in auditory HEI-OC1 cells.

Abstract
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.
AuthorsSu-Jin Kim, Bong-Gi Shin, In-Young Choi, Dong-Hyun Kim, Min-Cheol Kim, Noh-Yil Myung, Phil-Dong Moon, Jeong-Han Lee, Hyo-Jin An, Na-Hyung Kim, Joo-Young Lee, Hong-Seob So, Rae-Kil Park, Hyun-Ja Jeong, Jae-Young Um, Hyung-Min Kim, Seung-Heon Hong
JournalBiological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 32 Issue 2 Pg. 213-9 (Feb 2009) ISSN: 0918-6158 [Print] Japan
PMID19182378 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Drugs, Chinese Herbal
  • Indicators and Reagents
  • Reactive Oxygen Species
  • Tetrazolium Salts
  • Thiazoles
  • hwanggunchungyitang
  • Cadmium
  • Extracellular Signal-Regulated MAP Kinases
  • Caspase 9
  • thiazolyl blue
Topics
  • Animals
  • Blotting, Western
  • Cadmium (antagonists & inhibitors, metabolism, toxicity)
  • Caspase 9 (metabolism)
  • Cell Line
  • Cell Survival (drug effects)
  • Drugs, Chinese Herbal (therapeutic use)
  • Enzyme Activation (drug effects)
  • Extracellular Signal-Regulated MAP Kinases (metabolism)
  • Hair Cells, Auditory (drug effects, metabolism, pathology)
  • Hearing Disorders (chemically induced, prevention & control)
  • Humans
  • Indicators and Reagents
  • Mice
  • Organ Culture Techniques
  • Organ of Corti (drug effects, metabolism, pathology)
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species
  • Tetrazolium Salts
  • Thiazoles

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