Department of Otorhinolaryngology, Peking University Shenzhen Hospital, Shenzhen 518036, China.
Department of Otorhinolaryngology, Shenzhen Children's Hospital, Shenzhen 518034, China.
Biomed Pharmacother. 2024 Sep;178:117174. doi: 10.1016/j.biopha.2024.117174. Epub 2024 Aug 3.
Mangiferin(MGF) exhibits crucial biological roles, including antioxidant and anti-inflammatory functions. However, how to clearly elucidate the functioning mechanism of MGF for inhibiting cisplatin-induced hearing loss requires in-depth investigation. In this work, we aimed at gaining insight into how MGF functions as the protective agent against cisplatin-triggered ototoxicity using various assays. The variation for reactive oxygen species (ROS) concentrations was determined with MitoSOX-Red and 2',7'-Dichlorodihydrofluorescein diacetate staining (DCFH-DA). The protective function and corresponding mechanism of MGF in hair cell survival in the House Ear Institute-Organ of Corti (HEI-OC1) cell line were assessed using RNA sequencing (RNA-Seq). Our findings demonstrated that MGF significantly alleviated cisplatin-induced injury to hair cells in vitro, encompassing cell lines and cochlear explants, as well as in vivo models, including C57BL/6 J mice and zebrafish larvae. Mechanistic studies revealed that MGF reversed the increased accumulation of ROS and inhibited cell apoptosis through mitochondrial-mediated intrinsic pathway. Moreover, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting data indicated MGF protected against cisplatin-mediated ototoxicity via the mitogen-activated protein kinase pathway (MAPK). These findings demonstrated MGF has significant potential promise in combating cisplatin-induced ototoxicity, offering a foundation for expanded investigation into therapeutic approaches for auditory protection.
芒果苷（MGF）具有重要的生物学作用，包括抗氧化和抗炎功能。然而，要清楚阐明 MGF 抑制顺铂诱导的听力损失的作用机制，需要深入研究。在这项工作中，我们旨在通过各种测定方法深入了解 MGF 如何作为对抗顺铂诱发耳毒性的保护剂发挥作用。使用 MitoSOX-Red 和 2'，7'-二氯二氢荧光素二乙酸酯染色（DCFH-DA）测定活性氧（ROS）浓度的变化。使用 RNA 测序（RNA-Seq）评估 MGF 在体外（包括细胞系和耳蜗外植体）和体内模型（包括 C57BL/6J 小鼠和斑马鱼幼虫）中对毛细胞存活的保护作用及其相应机制。我们的研究结果表明，MGF 显著减轻了体外（包括细胞系和耳蜗外植体）和顺铂诱导的毛细胞损伤，以及体内模型（包括 C57BL/6J 小鼠和斑马鱼幼虫）。机制研究表明，MGF 通过线粒体介导的内在途径逆转了 ROS 的积累增加并抑制了细胞凋亡。此外，实时定量聚合酶链反应（RT-qPCR）和蛋白质印迹数据表明，MGF 通过丝裂原激活蛋白激酶途径（MAPK）保护毛细胞免受顺铂介导的耳毒性。这些发现表明 MGF 在对抗顺铂诱导的耳毒性方面具有显著的潜力，为听觉保护的治疗方法的进一步研究提供了基础。
