1. Academic Validation
  2. Protective effect of T-type calcium channel blocker flunarizine on cisplatin-induced death of auditory cells

Protective effect of T-type calcium channel blocker flunarizine on cisplatin-induced death of auditory cells

  • Hear Res. 2005 Jun;204(1-2):127-39. doi: 10.1016/j.heares.2005.01.011.
Hong-Seob So 1 Channy Park Hyung-Jin Kim Jung-Han Lee Sung-Yeol Park Jai-Hyung Lee Zee-Won Lee Hyung-Min Kim Federico Kalinec David J Lim Raekil Park
Affiliations

Affiliation

  • 1 Vestibulocochlear Research Center and Department of Microbiology, Korea Basic Science Institute, Taejon 305-333, Korea.
Abstract

Changes in intracellular Ca2+ level are involved in a number of intracellular events, including triggering of Apoptosis. The role of intracellular calcium mobilization in cisplatin-induced hair cell death, however, is still unknown. In this study, the effect of Calcium Channel blocker flunarizine (Sibelium), which is used to prescribe for vertigo and tinnitus, on cisplatin-induced hair cell death was investigated in a cochlear organ of Corti-derived cell line, HEI-OC1, and the neonatal (P2) rat organ of Corti explant. Cisplatin induced apoptotic cell death showing nuclear fragmentation, DNA ladder, and TUNEL positive in both HEI-OC1 and primary organ of Corti explant. Flunarizine significantly inhibited the cisplatin-induced Apoptosis. Unexpectedly, flunarizine increased the intracellular calcium ([Ca2+]i) levels of HEI-OC1. However, the protective effect of flunarizine against cisplatin was not mediated by modulation of intracellular calcium level. Treatment of cisplatin resulted in ROS generation and lipid peroxidation in HEI-OC1. Flunarizine did not attenuate ROS production but inhibited lipid peroxidation and mitochondrial permeability transition in cisplatin-treated cells. This result suggests that the protective mechanism of flunarizine on cisplatin-induced cytotoxicity is associated with direct inhibition of lipid peroxidation and mitochondrial permeability transition.

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