Protective effect of T-type calcium channel blocker flunarizine on cisplatin-induced death of auditory cells.
Hear Res
; 204(1-2): 127-39, 2005 Jun.
Article
en En
| MEDLINE
| ID: mdl-15925198
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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Banco de datos:
MEDLINE
Asunto principal:
Bloqueadores de los Canales de Calcio
/
Flunarizina
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Cisplatino
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Células Ciliadas Auditivas
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Pérdida Auditiva Sensorineural
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Antineoplásicos
Límite:
Animals
Idioma:
En
Año:
2005
Tipo del documento:
Article