Cisplatin 유발성 이독성에 대한 Tempol의 보호효과

Abstract

One of the major side effects of cisplatin chemotherapy is hearing loss. Ototoxicity disturbs treatment and often reduces the dosage of the cisplatin chemotherapy. This study aimed to investigate the effect of tempol on cisplatin-induced ototoxicity in an auditory cell line. Cultured HEI-OC1 cells were exposed to 30μM of cisplatin for 24 hours with or without pre-treatment with tempol, Cell viability was determined by the MTT assay. Cells undergoing apoptosis were identified using Hoechst 33258 staining and flow cytometry. Western blot analysis was done to determine whether tempol inhibited cisplatin-induced C-PARP, C-Caspase and mNOS activation. Intracellular reactive oxygen species(ROS) were tested to investigate whether tempol was able to scavenge cisplain-induced ROS accumulation. Confocal microscopic studies of the mitochondria was done and mitochondrial membrane potential was tested to investigate whether tempoal was able to protect cisplatin-induced mitochondrial dysfunction. The cisplatin-treated group showed decreased cell viability, increase in apoptotic features and markers, increase in ROS accumulation and increase in mitochondrial dysfunction. Pre-treatment of tempol before cisplatin exposure significantly increased cell viability and reduced apoptotic features, ROS production and mitochondrial dysfunction. These results demonstrate that tempol inhibited cisplatin-induced cytotoxicity in the auditory cell line and tempol could play a preventive role against cisplatin-induced ototoxicity.