Biology Department, Western Kentucky University, Bowling Green, KY, 42101-1080, USA.
Neurotox Res. 2021 Feb;39(1):36-41. doi: 10.1007/s12640-020-00188-y. Epub 2020 Mar 27.
Cisplatin is a platinum-based chemotherapy compound effective against a variety of cancers. However, it can cause increased reactive oxygen species (ROS) production in auditory and vestibular tissue leading to permanent hearing and balance loss. The amino acid, L-serine, has been shown to reduce ROS in some tissue types. In this project, we first investigated whether L-serine could reduce cisplatin-mediated ROS generation in zebrafish utricular tissue culture using spectrophotometry and the fluorescent ROS detector dye, HDCFDA. Then, we examined whether L-serine could prevent the effect of cisplatin against cellular viability in the mouse auditory hybridoma cell line, HEI-OC1, using the spectrophotometric (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. As a final step, we used HDCFDA dye and flow cytometry analysis to determine if L-serine could counteract the effect of cisplatin on ROS production in this cell line. We found that cisplatin and L-serine treatment may influence ROS production in utricular tissue. Further, although L-serine did not counteract the effect of cisplatin against HEI-OC1 cellular viability, the amino acid did prevent the platinum compound's effect to increase ROS in these cells. These results suggest that L-serine may act in auditory and vestibular tissues as an effective protectant against cisplatin-mediated toxicity.
顺铂是一种基于铂的化疗化合物,对多种癌症有效。然而,它会导致听觉和前庭组织中活性氧(ROS)的产生增加,从而导致永久性听力和平衡丧失。氨基酸 L-丝氨酸已被证明可以减少某些组织类型中的 ROS。在这个项目中,我们首先使用分光光度法和荧光 ROS 检测染料 HDCFDA 研究了 L-丝氨酸是否可以减少斑马鱼耳石组织培养物中顺铂介导的 ROS 生成。然后,我们使用分光光度法(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐)(MTT)测定法检查了 L-丝氨酸是否可以预防顺铂对小鼠听觉杂交瘤细胞系 HEI-OC1 细胞活力的影响。作为最后一步,我们使用 HDCFDA 染料和流式细胞术分析来确定 L-丝氨酸是否可以抵抗顺铂对该细胞系中 ROS 产生的影响。我们发现顺铂和 L-丝氨酸处理可能会影响耳石组织中的 ROS 产生。此外,尽管 L-丝氨酸不能抵抗顺铂对 HEI-OC1 细胞活力的影响,但该氨基酸确实可以防止铂化合物增加这些细胞中的 ROS。这些结果表明,L-丝氨酸可能在听觉和前庭组织中作为一种有效的保护剂,对抗顺铂介导的毒性。