Cho S I, Lee J H, Park J H, Do N Y
Department of Otolaryngology-Head and Neck Surgery, Chosun University School of Medicine, Gwangju, South Korea.
J Laryngol Otol. 2014 Apr;128(4):350-355. doi: 10.1017/S0022215114000553.
Ototoxicity due to cisplatin therapy interferes with treatment and often forces a reduction in the dosage, duration and frequency of the cisplatin therapy. (-)-Epigallocatechin-3-gallate is known to have the highest antioxidant potency among all tea catechins. This study aimed to investigate the effect of (-)-epigallocatechin-3-gallate on cisplatin ototoxicity in an auditory cell line: House Ear Institute-Organ of Corti 1 cells.
Cultured House Ear Institute-Organ of Corti 1 cells were exposed to cisplatin with or without pre-treatment with (-)-epigallocatechin-3-gallate. Cell viability was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Hoechst 33258 staining was used to identify cells undergoing apoptosis. Western blot analysis was conducted to determine whether (-)-epigallocatechin-3-gallate inhibited cisplatin-induced caspase activation. Intracellular reactive oxygen species production was examined to investigate whether (-)-epigallocatechin-3-gallate was capable of scavenging cisplatin-induced reactive oxygen species accumulation.
Cell viability significantly increased in cells pre-treated with (-)-epigallocatechin-3-gallate compared with cells exposed to cisplatin alone. Cisplatin increased cleaved caspase-3 on Western blot analysis; however, pre-treatment with (-)-epigallocatechin-3-gallate inhibited the expression of caspase-3. (-)-Epigallocatechin-3-gallate attenuated reactive oxygen species production and apoptosis in House Ear Institute-Organ of Corti 1 cells.
(-)-Epigallocatechin-3-gallate protected against cisplatin cytotoxicity through anti-apoptotic and anti-oxidative effects. Therefore, (-)-epigallocatechin-3-gallate could play a preventive role in cisplatin-induced ototoxicity.
顺铂治疗引起的耳毒性会干扰治疗，且常常迫使减少顺铂治疗的剂量、疗程和频率。（-）-表没食子儿茶素-3-没食子酸酯在所有茶儿茶素中具有最高的抗氧化能力。本研究旨在调查（-）-表没食子儿茶素-3-没食子酸酯对听觉细胞系——House Ear Institute-Organ of Corti 1细胞中顺铂耳毒性的影响。
将培养的House Ear Institute-Organ of Corti 1细胞暴露于顺铂，其中一组在暴露前用（-）-表没食子儿茶素-3-没食子酸酯预处理。使用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐法评估细胞活力。采用Hoechst 33258染色来鉴定正在经历凋亡的细胞。进行蛋白质免疫印迹分析以确定（-）-表没食子儿茶素-3-没食子酸酯是否抑制顺铂诱导的半胱天冬酶激活。检测细胞内活性氧的产生，以研究（-）-表没食子儿茶素-3-没食子酸酯是否能够清除顺铂诱导的活性氧积累。
与仅暴露于顺铂的细胞相比，用（-）-表没食子儿茶素-3-没食子酸酯预处理的细胞活力显著增加。蛋白质免疫印迹分析显示顺铂增加了裂解的半胱天冬酶-3的表达；然而，用（-）-表没食子儿茶素-3-没食子酸酯预处理可抑制半胱天冬酶-3的表达。（-）-表没食子儿茶素-3-没食子酸酯减轻了House Ear Institute-Organ of Corti 1细胞中的活性氧产生和凋亡。
（-）-表没食子儿茶素-3-没食子酸酯通过抗凋亡和抗氧化作用保护细胞免受顺铂的细胞毒性。因此，（-）-表没食子儿茶素-3-没食子酸酯可能在顺铂诱导的耳毒性中发挥预防作用。
