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 (Cd2+) is a heavy metal and a potent carcinogen implicated in tumor development through occupational and environmental exposure. However, the auditory effect of Cd2+ is not poorly understood. The purpose of the present study was to investigate whether HGCYT prevent the ototoxic effects induced by Cd2+ 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 Cd2+. In addition, we observed that cochlear hair cells in middle turn were damaged by Cd2+. However, HGCYT prevented the destruction of hair cell arrays of the rat primary organ of Corti explants in the presence of Cd2+. These results support the notion that ROS are involved in Cd2+ ototoxicity and suggest HGCYT therapeutic usefulness, against Cd2+-induced activation of caspase-9 and ERK.