ABSTRACT

Objectives

In cancer survivors, chemotherapy-associated adverse neurological effects are described as side effects in non-targeted tissue. We investigated the role of redox-imbalance in neuronal damage by a relative low dose of Docetaxel (DTX).

Methods

The neuroblastoma cells (SH-SY5Y cells) were exposed to DTX at a dose of 1.25 nM for 6 h. Antioxidant defenses (i.e. ascorbic acid, glutathione, and catalase) and lipid oxidation products (i.e. F₂-isoprostanes) were evaluated. To investigate cell ultrastructure and tubulin localisation, transmission electron microscopy (TEM) and immunofluorescence techniques were applied.

Results

In the SH-SY5Y cells, DTX induced a significant reduction of total glutathione (P < 0.001) and ascorbic acid (P < 0.05), and an increase in both total F₂-Isoprostanes (P < 0.05) and catalase activity (P < 0.05), as compared to untreated cells. Additionally, TEM showed a significant increase in cells with apoptotic characteristics. Immunolocalisation of tubulin showed a compromised cytoskeletal organisation.

Discussion

The investigated sublethal dose of DTX, to which non-targeted cells may be exposed throughout the duration of chemotherapy treatment, induces a redox imbalance resulting in a specific modulation of the antioxidant response. This study provides new insights into DTX-induced cellular mechanisms useful for evaluating whether the concomitant use of antioxidants associated with chemotherapy mitigates chemotherapy side effects in cancer survivors.

中文翻译：

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多西紫杉醇在神经母细胞瘤 SH-SY5Y 细胞中诱导的氧化还原失衡：多西紫杉醇诱导的神经元损伤的研究

摘要

目标

在癌症幸存者中，化疗相关的不良神经系统影响被描述为非靶向组织的副作用。我们通过相对低剂量的多西紫杉醇 (DTX) 研究了氧化还原失衡在神经元损伤中的作用。

方法

神经母细胞瘤细胞（SH-SY5Y 细胞）以 1.25 nM 的剂量暴露于 DTX 6 小时。评估了抗氧化防御（即抗坏血酸、谷胱甘肽和过氧化氢酶）和脂质氧化产物（即F _{2 -异前列腺素）。}为了研究细胞超微结构和微管蛋白定位，应用了透射电子显微镜（TEM）和免疫荧光技术。

结果

在 SH-SY5Y 细胞中，DTX 可显着降低总谷胱甘肽 ( P  < 0.001) 和抗坏血酸 ( P  < 0.05)，并增加总 F ₂ -异前列腺素 ( P  < 0.05) 和过氧化氢酶活性 ( P  < 0.05)，与未处理的细胞相比。此外，TEM 显示具有凋亡特征的细胞显着增加。微管蛋白的免疫定位显示细胞骨架组织受损。

讨论

所研究的亚致死剂量的 DTX，非靶向细胞可能在整个化疗治疗期间暴露，诱导氧化还原失衡，导致抗氧化反应的特定调节。这项研究为 DTX 诱导的细胞机制提供了新的见解，可用于评估与化疗相关的抗氧化剂的同时使用是否可以减轻癌症幸存者的化疗副作用。