Vertigo Research Today is a free monthly online journal that collates and summarizes the latest research about Vertigo, including details on causes, symptoms, treatment, dizziness. | ||||||||
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Protective effect of T-type calcium channel blocker flunarizine on cisplatin-induced death of auditory cells.So HS, Park C, Kim HJ, Lee JH, Park SY, Lee JH, Lee ZW, Kim HM, Kalinec F, Lim DJ, Park R Vestibulocochlear Research Center and Department of Microbiology, Korea Basic Science Institute, Taejon 305-333, Korea. 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. Published 31 May 2005 in Hear Res, 204(1): 127-39.
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