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Thymoquinone prevents cisplatin neurotoxicity in primary DRG neurons
NeuroToxicology ( IF 3.4 ) Pub Date : 2018-09-15 , DOI: 10.1016/j.neuro.2018.09.001
Ramazan Üstün , Elif Kaval Oğuz , Ayşe Şeker , Hasan Korkaya

Chemotherapy-induced peripheral neuropathy (CIPN) is a substantial, dose-limiting adverse effect that occurs in cancer patients. Cis-dichlorodiamine (II) platinum (CDDP, cisplatin) is a platinum-based chemotherapeutic agent that causes severe acute and chronic peripheral neuropathies in 30% of cancer patients. Thymoquinone (TQ), a leading bioactive constituent of Nigella sativa seeds, has been reported to have antioxidant, anti-inflammatory, anti-neoplastic and neuroprotective properties. Dorsal root ganglia (DRG) include different classes of primary sensory neurons, such as nociceptors, mechanoreceptors, and proprioceptive neurons. Here, we investigated the neuroprotective activity of TQ against cisplatin neurotoxicity in cultured DRG neurons. We prepared neuronal cultures from DRGs of adult mice, pre-treated them with or without varying doses of TQ prior to exposure of cells to cisplatin. The preparations were viewed under the scope before and after the treatment at 24 h, 48 h, and 72 h time points. We analyzed neuronal cell viability and neurite outgrowths, and evaluated morphologic changes of neuronal or non-neuronal cells. TQ significantly increases the ability to extend neurites and neuronal cell viability when compared to the culture conditions which were treated with cisplatin only. Although we provide compelling evidence for the protective activity of TQ against chemotherapy-induced neurotoxicity, further detailed investigations in preclinical settings are warranted for its clinical use.



中文翻译:

胸腺醌可预防原发性DRG神经元中的顺铂神经毒性

化疗引起的周围神经病(CIPN)是一种在癌症患者中发生的严重的,剂量限制性的不良反应。顺式二氯二胺(II)铂(CDDP,顺铂)是一种基于铂的化学治疗剂,可在30%的癌症患者中引起严重的急性和慢性周围神经病。百里香(TQ)是变种(Nigella sativa)的主要生物活性成分据报道,种子具有抗氧化,抗炎,抗肿瘤和神经保护的特性。背根神经节(DRG)包括不同类别的初级感觉神经元,例如伤害感受器,机械感受器和本体感受神经元。在这里,我们调查了培养的DRG神经元中TQ对顺铂神经毒性的神经保护活性。我们从成年小鼠的DRGs中制备了神经元培养物,在将细胞暴露于顺铂之前用或不使用不同剂量的TQ对其进行了预处理。在24小时,48小时和72小时的时间点之前和之后的处理范围内查看制剂。我们分析了神经元细胞的活力和神经突的生长,并评估了神经元或非神经元细胞的形态变化。与仅用顺铂处理的培养条件相比,TQ显着增加了延伸神经突和神经元细胞活力的能力。尽管我们提供了有关TQ对化学疗法诱导的神经毒性的保护活性的令人信服的证据,但仍需要在临床前环境中进行进一步详细的研究以用于其临床用途。

更新日期:2018-09-15
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