Cisplatin‑induced cytotoxicity, such as nephrotoxicity, neurotoxicity and ototoxicity, restricts the clinical application of this compound. Panax notoginseng Saponins (PNS) exhibit potent free radical scavenging and antioxidant activity. PNS have been demonstrated to reduce cisplatin‑induced nephrotoxicity and neurotoxicity. The present study investigated the ability of PNS to protect the auditory HEI‑OC1 cell line against ototoxicity induced by cisplatin. PNS induced activation of the AKT/nuclear factor erythroid 2‑related factor 2 (Nrf2) signaling pathway. Following pretreatment with PNS, HEI‑OC1 cells were treated with cisplatin and cultured for 24 h. The viability of HEI‑OC1 cells was examined using a Cell Counting Kit‑8 assay. Double staining analysis was used to measure cell apoptosis. The ability of PNS to reduce reactive oxygen species (ROS) levels was assessed by flow cytometry. The levels of phosphorylated (p)‑AKT, heme oxygenase 1 (HO‑1), NAD(P)H quinone dehydrogenase 1 (NQO1), glutamate‑cysteine ligase catalytic (GCLC) and Nrf2 were measured by western blotting. HEI‑OC1 cells that were pretreated with PNS exhibited significantly increased cell viability compared with that noted in cells treated only with cisplatin. In addition, PNS suppressed the induction of apoptosis and ROS production following cisplatin treatment. The upregulation of NQO1, HO‑1 and GCLC expression in PNS‑pretreated cells was associated with p‑AKT levels and the activation of Nrf2. These findings suggested that PNS protected auditory cells against ototoxicity induced by cisplatin by activating AKT/Nrf2 signaling. PNS may serve as a potential candidate in regulating cisplatin‑induced cytotoxicity.

译文

:顺铂诱导的细胞毒性,例如肾毒性,神经毒性和耳毒性,限制了该化合物的临床应用。三七总皂甙(PNS)具有很强的清除自由基和抗氧化的作用。已证明PNS可以减少顺铂引起的肾毒性和神经毒性。本研究调查了PNS保护听觉HEI-OC1细胞系免受顺铂诱导的耳毒性的能力。 PNS诱导AKT /核因子红系2相关因子2(Nrf2)信号通路的激活。用PNS预处理后,用顺铂处理HEI-OC1细胞并培养24小时。使用Cell Counting Kit-8分析法检查了HEI‑OC1细胞的生存能力。双重染色分析用于测量细胞凋亡。通过流式细胞仪评估PNS降低活性氧(ROS)水平的能力。通过蛋白质印迹法测量了磷酸化(p)-AKT,血红素加氧酶1(HO-1),NAD(P)H醌脱氢酶1(NQO1),谷氨酸半胱氨酸连接酶催化(GCLC)和Nrf2的水平。与仅用顺铂处理的细胞相比,经PNS预处理的HEI‑OC1细胞显示出明显提高的细胞活力。此外,PNS抑制顺铂治疗后细胞凋亡的诱导和ROS的产生。 PNS预处理的细胞中NQO1,HO-1和GCLC表达的上调与p-AKT水平和Nrf2的激活有关。这些发现表明,PNS通过激活AKT / Nrf2信号传导保护听觉细胞免受顺铂诱导的耳毒性。 PNS可能是调节顺铂诱导的细胞毒性的潜在候选药物。

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