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五味子乙素通过抑制细胞氧化应激和细胞凋亡来保护内耳毛细胞免受顺铂的损伤。

Schisandrin B protect inner hair cells from cisplatin by inhibiting celluar oxidative stress and apoptosis.

机构信息

Department of Otolaryngology Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710000, China.

Department of Otolaryngology Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710000, China.

出版信息

Toxicol In Vitro. 2024 Aug;99:105852. doi: 10.1016/j.tiv.2024.105852. Epub 2024 May 23.

Abstract

Cisplatin is an effective chemotherapeutic agent; however, ototoxicity is one of its negative effects that greatly limits the use of cisplatin in clinical settings. Previous research has shown that the most important process cisplatin damage to inner ear cells, such as hair cells (HCs), is the excessive production and accumulation of ROS. Schisandrin B (SchB), is a low-toxicity, inexpensive, naturally occurring antioxidant with a variety of pharmacological effects. Therefore, the potential antioxidant effects of SchB may be useful for cisplatin ototoxicity treatment. In this study, the effects of SchB on cochlear hair cell viability, ROS levels, and expression of apoptosis-related molecules were evaluated by CCK-8, immunofluorescence, flow cytometry, and qRT-PCR, as well as auditory brainstem response (ABR) and dysmorphic product otoacoustic emission (DPOAE) tests to assess the effects on inner ear function. The results showed that SchB treatment increased cell survival, prevented apoptosis, and reduced cisplatin-induced ROS formation. SchB treatment reduced the loss of cochlear HCs caused by cisplatin in exosome culture. In addition, SchB treatment attenuated cisplatin-induced hearing loss and HC loss in mice. This study demonstrates the ability of SchB to inhibit cochlear hair cell apoptosis and ROS generation and shows its potential therapeutic effect on cisplatin ototoxicity.

摘要

顺铂是一种有效的化疗药物;然而,耳毒性是其负面影响之一,极大地限制了顺铂在临床环境中的应用。先前的研究表明,顺铂对内耳细胞(如毛细胞[HCs])的损伤最重要的过程是活性氧(ROS)的过度产生和积累。五味子乙素(SchB)是一种低毒性、廉价、天然存在的抗氧化剂,具有多种药理学作用。因此,SchB 的潜在抗氧化作用可能对顺铂耳毒性的治疗有用。在这项研究中,通过 CCK-8、免疫荧光、流式细胞术和 qRT-PCR 评估了 SchB 对耳蜗毛细胞活力、ROS 水平和凋亡相关分子表达的影响,以及听觉脑干反应(ABR)和畸变产物耳声发射(DPOAE)测试评估对内耳功能的影响。结果表明,SchB 处理可增加细胞存活、预防细胞凋亡,并减少顺铂诱导的 ROS 形成。SchB 处理可减少外泌体培养中顺铂引起的耳蜗 HCs 丢失。此外,SchB 处理可减轻顺铂引起的小鼠听力损失和 HC 损失。这项研究证明了 SchB 抑制耳蜗毛细胞凋亡和 ROS 生成的能力,并显示了其对顺铂耳毒性的潜在治疗作用。

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