Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea.
J Appl Toxicol. 2013 Feb;33(2):125-33. doi: 10.1002/jat.1729. Epub 2011 Dec 6.
Cisplatin is a very effective anticancer drug and generates reactive oxygen species (ROS) such as superoxide anions that can deplete antioxidant protective molecules in the cochlea. These processes result in the death of cochlear hair cells by induction of apoptosis. Apocynin, which is used as a specific nicotinamide adenine dinucleotide phosphate oxidase inhibitor, has a preventive effect for intracellular ROS generation. In this study, the effect of apocynin was investigated in a cochlear organ of Corti-derived cell line, HEI-OC1 cells, and in transgenic zebrafish (Brn3C: EGFP). To investigate the protective effects of apocynin, HEI-OC1 cells were treated with various concentrations of apocynin and a 20 µm concentration of cisplatin, simultaneously. An in vivo study of transgenic zebrafish (Brn3C: EGFP) was used to investigate the protective effects of apocynin on cisplatin-induced hair cell death. In an in vitro study, apocynin appeared to protect against cisplatin-induced apoptotic features on Hoechst 33258 staining in the HEI-OC1 cells. Treatment of the HEI-OC1 cells with 100 µm of apocynin, significantly decreased caspase-3 activity. Treatment of the cells with a 100 µm concentration of apocynin and a 20 µm concentration of cisplatin significantly decreased the intracellular ROS production. In the in vivo study, apocynin significantly decreased the TUNEL reaction and prevented cisplatin-induced hair cell loss of the neuromasts in the transgenic zebrafish at low concentrations (125 and 250 µm). These findings suggest that apocynin has antioxidative effects and prevents cisplatin-induced apoptotic cell death in HEI-OC1 cells as well as in zebrafish.
顺铂是一种非常有效的抗癌药物，会产生活性氧物种（ROS），如超氧阴离子，从而耗尽耳蜗中的抗氧化保护分子。这些过程导致毛细胞通过诱导细胞凋亡而死亡。阿朴肉桂酸，用作特异性烟酰胺腺嘌呤二核苷酸磷酸氧化酶抑制剂，对细胞内 ROS 的产生具有预防作用。在这项研究中，阿朴肉桂酸在耳蜗器官衍生细胞系 HEI-OC1 细胞和转基因斑马鱼（Brn3C：EGFP）中进行了研究。为了研究阿朴肉桂酸的保护作用，同时用不同浓度的阿朴肉桂酸和 20 µm 浓度的顺铂处理 HEI-OC1 细胞。使用转基因斑马鱼（Brn3C：EGFP）的体内研究来研究阿朴肉桂酸对顺铂诱导的毛细胞死亡的保护作用。在体外研究中，阿朴肉桂酸似乎可以保护 HEI-OC1 细胞免受顺铂诱导的凋亡特征，如 Hoechst 33258 染色。用 100 µm 的阿朴肉桂酸处理 HEI-OC1 细胞，可显著降低 caspase-3 活性。用 100 µm 浓度的阿朴肉桂酸和 20 µm 浓度的顺铂处理细胞可显著降低细胞内 ROS 的产生。在体内研究中，阿朴肉桂酸以低浓度（125 和 250 µm）显著降低 TUNEL 反应并防止转基因斑马鱼中顺铂诱导的毛细胞损失。这些发现表明，阿朴肉桂酸具有抗氧化作用，可预防 HEI-OC1 细胞和斑马鱼中顺铂诱导的细胞凋亡。
